RESUMEN
A bibliometric analysis of studies dedicated to autoimmune gastritis (AIG) recently published demonstrated a noteworthy surge in publications over the last three years. This can be explained by numerous publications from different regions of the world reporting the results of several studies that stimulated reassessment of our view of AIG as a precancerous condition. Follow-up studies and retrospective analyses showed that the risk of gastric cancer (GC) in AIG patients is much lower than expected if the patients ever being infected with Helicobacter pylori (H. pylori) were excluded. The low prevalence of precancerous lesions, such as the incomplete type of intestinal metaplasia, may explain the low risk of GC in AIG patients because the spasmolytic polypeptide-expressing metaplasia commonly observed in AIG does not involve clonal reprogramming of the gastric gland and can be considered as an adaptive change rather than a true precancerous lesion. However, changes in gastric secretion due to the progression of gastric atrophy during the course of AIG cause changes in the gastric mic-robiome, stimulating the growth of bacterial species such as streptococci, which may promote the development of precancerous lesions and GC. Thus, Streptococcus anginosus exhibited a robust proinflammatory response and induced the gastritis-atrophy-metaplasia-dysplasia sequence in mice, reproducing the well-established process for carcinogenesis associated with H. pylori. Prospective studies in H. pylori-naïve patients evaluating gastric microbiome changes during the long-term course of AIG might provide an explanation for the enigmatic increase in GC incidence in the last decades in younger cohorts, which has been reported in economically developed countries.
Asunto(s)
Enfermedades Autoinmunes , Bibliometría , Mucosa Gástrica , Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Lesiones Precancerosas , Neoplasias Gástricas , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/patología , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/epidemiología , Humanos , Gastritis/inmunología , Gastritis/microbiología , Gastritis/epidemiología , Gastritis/patología , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/inmunología , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/aislamiento & purificación , Helicobacter pylori/inmunología , Helicobacter pylori/patogenicidad , Lesiones Precancerosas/inmunología , Lesiones Precancerosas/microbiología , Lesiones Precancerosas/patología , Lesiones Precancerosas/epidemiología , Animales , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/epidemiología , Mucosa Gástrica/patología , Mucosa Gástrica/inmunología , Mucosa Gástrica/microbiología , Metaplasia , Factores de Riesgo , Estómago/patología , Estómago/inmunología , Estómago/microbiología , Microbioma Gastrointestinal/inmunología , RatonesRESUMEN
Persistent high-risk human papillomaviruses (HR HPVs) infection leads to the development of squamous intraepithelial lesions in cervical cells that may lead to cancer. The telomere length, telomerase activity, and species composition of the vaginal microbiome may influence the dynamic of changes and the process of carcinogenesis. In the present study, we analyze relative telomere length (RTL), relative hTERT expression (gene for the telomerase component-reverse transcriptase) in cervical smear cells and vaginal microbiomes. Total RNA and DNA were isolated from tissue samples of 109 patients from the following groups: control, carrier, low-grade or high-grade squamous intraepithelial lesion (L SIL and H SIL, respectively), and cancer. The quantitative PCR method was used to measure telomere length and telomerase expression. Vaginal microbiome bacteria were divided into community state types using morphotype criteria. Significant differences between histopathology groups were confirmed for both relative telomere length and relative hTERT expression (p < 0.001 and p = 0.001, respectively). A significant difference in RTL was identified between carriers and H SIL (p adj < 0.001) groups, as well as between carriers and L SIL groups (p adj = 0.048). In both cases, RTL was lower among carriers. The highest relative hTERT expression level was recorded in the H SIL group, and the highest relative hTERT expression level was recorded between carriers and the H SIL group (p adj < 0.001). A correlation between genotype and biocenosis was identified for genotype 16+A (p < 0.001). The results suggest that identification of HPV infection, telomere length assessment, and hTERT expression measurement together may be more predictive than each of these analyses performed separately.
Asunto(s)
Microbiota , Infecciones por Papillomavirus , Lesiones Precancerosas , Telomerasa , Telómero , Neoplasias del Cuello Uterino , Vagina , Humanos , Femenino , Telomerasa/metabolismo , Telomerasa/genética , Vagina/microbiología , Vagina/virología , Microbiota/genética , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/genética , Adulto , Telómero/metabolismo , Telómero/genética , Persona de Mediana Edad , Lesiones Precancerosas/virología , Lesiones Precancerosas/microbiología , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/microbiología , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Homeostasis del Telómero , Papillomaviridae/genéticaRESUMEN
Reports of Helicobacter pylori (Hp)-naïve gastric neoplasm (HpNGN) cases have been rapidly increasing due to the recent increase in the Hp-naïve population in Japan. Most HpNGNs exhibit the gastric immunophenotype and a low malignant potential regardless of histological type. Especially, foveolar-type gastric adenoma (FGA) and intestinal-type gastric dysplasia (IGD) rarely progress to invasive carcinoma. FGA is a foveolar epithelial neoplasm that occurs in the fundic gland (oxyntic gland) mucosa and is classified as the flat type or raspberry type (FGA-RA). The flat type is a large, whitish flatly elevated lesion while FGA-RA is a small reddish polyp. Genomically, the flat type is characterized by APC and KRAS gene mutations and FGA-RA by a common single nucleotide variant in the KLF4 gene. This KLF4 single-nucleotide variant reportedly induces gastric foveolar epithelial tumorigenesis and activates both cell proliferation and apoptosis, leading to its slow-growing nature. IGD consists of an intestinalized epithelial dysplasia that develops in the pyloric gland mucosa, characterized as a superficial depressed lesion surrounded by raised mucosa showing a gastritis-like appearance. Immunohistochemically, it exhibits an intestinal or gastrointestinal phenotype and, frequently, p53 overexpression. Thus, IGD shows unique characteristics in HpNGNs and a potential multistep tumorigenic process.
Asunto(s)
Adenoma , Mucosa Gástrica , Helicobacter pylori , Factor 4 Similar a Kruppel , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/microbiología , Adenoma/patología , Adenoma/microbiología , Mucosa Gástrica/patología , Mucosa Gástrica/microbiología , Helicobacter pylori/aislamiento & purificación , Infecciones por Helicobacter/patología , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/microbiología , Lesiones Precancerosas/patología , Lesiones Precancerosas/microbiología , Proteínas Proto-Oncogénicas p21(ras)/genética , Mutación , Estómago/patología , Estómago/microbiologíaRESUMEN
BACKGROUND: Microbiota may be associated with esophageal squamous cell carcinoma (ESCC) development. However, it is not known the predictive value of microbial biomarkers combining epidemiological factors for the early detection of ESCC and precancerous lesions. METHODS: A total of 449 specimens (esophageal swabs and saliva) were collected from 349 participants with different esophageal statuses in China to explore and validate ESCC-associated microbial biomarkers from genes level to species level by 16S rRNA sequencing, metagenomic sequencing and real-time quantitative polymerase chain reaction. RESULTS: A bacterial biomarker panel including Actinomyces graevenitzii (A.g_1, A.g_2, A.g_3, A.g_4), Fusobacteria nucleatum (F.n_1, F.n_2, F.n_3), Haemophilus haemolyticus (H.h_1), Porphyromonas gingivalis (P.g_1, P.g_2, P.g_3) and Streptococcus australis (S.a_1) was explored by metagenomic sequencing to early detect the participants in Need group (low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia and ESCC) vs participants without these lesions as the Noneed group. Significant quantitative differences existed for each microbial target in which the detection efficiency rate was higher in saliva than esophageal swab. In saliva, the area under the curve (AUC) based on the microbial biomarkers (A.g_4 â© P.g_3 â© H.h_1 â© S.a_1 â© F.n_2) was 0.722 (95% CI 0.621-0.823) in the exploration cohort. Combining epidemiological factors (age, smoking, drinking, intake of high-temperature food and toothache), the AUC improved to 0.869 (95% CI 0.802-0.937) in the exploration cohort, which was validated with AUC of 0.757 (95% CI 0.663-0.852) in the validation cohort. CONCLUSIONS: It is feasible to combine microbial biomarkers in saliva and epidemiological factors to early detect ESCC and precancerous lesions in China.
Asunto(s)
Detección Precoz del Cáncer , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Lesiones Precancerosas , Humanos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/microbiología , Masculino , Femenino , Persona de Mediana Edad , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/microbiología , China/epidemiología , Carcinoma de Células Escamosas de Esófago/diagnóstico , Carcinoma de Células Escamosas de Esófago/epidemiología , Carcinoma de Células Escamosas de Esófago/microbiología , Detección Precoz del Cáncer/métodos , Anciano , Saliva/microbiología , ARN Ribosómico 16S/genética , Microbiota , Biomarcadores de Tumor , Adulto , Metagenómica/métodos , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: Non-cardia gastric cancer remains a major cause of cancer-related mortality worldwide, despite declining incidence rates in many industrialized countries. The development of intestinal-type gastric cancer occurs through a multistep process in which normal mucosa is sequentially transformed into hyperproliferative epithelium, followed by metaplastic processes leading to carcinogenesis. Chronic infection with Helicobacter pylori is the primary etiological agent that causes chronic inflammation of the gastric mucosa, induces atrophic gastritis, and can lead to intestinal metaplasia and dysplasia. Both intestinal metaplasia and dysplasia are precancerous lesions, in which gastric cancer is more likely to occur. Atrophic gastritis often improves after eradication of Helicobacter pylori; however, the occurrence of intestinal metaplasia has been traditionally regarded as "the point of no return" in the carcinogenesis sequence. Helicobacter pylori eradication heals non-atrophic chronic gastritis, may lead to regression of atrophic gastritis, and reduces the risk of gastric cancer in patients with these conditions. In this article, we discuss the pathogenesis, epigenomics, and reversibility of intestinal metaplasia and briefly touch upon potential treatment strategy. CONCLUSIONS: Gastric intestinal metaplasia no longer appears to be an irreversible precancerous lesion. However, there are still many controversies regarding the improvement of intestinal metaplasia after Helicobacter pylori eradication.
Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Metaplasia , Lesiones Precancerosas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/etiología , Metaplasia/patología , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/patología , Lesiones Precancerosas/patología , Lesiones Precancerosas/microbiología , Carcinogénesis/patología , Gastritis Atrófica/patología , Gastritis Atrófica/microbiología , Mucosa Gástrica/patología , Mucosa Gástrica/microbiología , Intestinos/patología , Intestinos/microbiologíaRESUMEN
The objective of this meta-analysis is to delineate the association between H. pylori CagA serological status and the prevalence of gastric precancerous lesions (GPL). We searched peer-reviewed articles up to October 2023. The extraction of data from the included studies was carried out as well as the quality assessment. Pooled effect sizes were calculated using a random effect model. Thirteen studies met the inclusion criteria, comprising 2728 patients with GPL and 17â 612 controls. The aggregate odds ratio (OR) for the association between serum CagA and GPL was 2.74 (95% CIâ =â 2.25-3.32; P â =â 0.00; I 2 â =â 60.4%), irrespective of H. pylori infection status. Within the H. pylori -infected cohort, the OR was 2.25 (95% CIâ =â 1.99-2.56; P â =â 0.00; I 2 â =â 0.0%). Conversely, among the non-infected individuals, the OR was 1.63 (95% CIâ =â 1.04-2.54; P â =â 0.038; I 2 â =â 0.0%). Heterogeneity was explored using subgroup and meta-regression analyses, indicating that the variability between studies likely stemmed from differences in disease classification. Our results demonstrated robustness and negligible publication bias. The meta-analysis underscores a more pronounced association between H. pylori CagA seropositivity and the risk of developing GPL than between seronegativity and the same risk, irrespective of H. pylori infection status at the time. Additionally, the strength of the association was heightened in the presence of an active H. pylori infection. The implications of these findings advocate for the utility of CagA serostatus as a potential biomarker for screening GPL.
Asunto(s)
Antígenos Bacterianos , Proteínas Bacterianas , Infecciones por Helicobacter , Helicobacter pylori , Lesiones Precancerosas , Neoplasias Gástricas , Humanos , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/sangre , Helicobacter pylori/inmunología , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/microbiología , Proteínas Bacterianas/inmunología , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/sangre , Neoplasias Gástricas/inmunología , Lesiones Precancerosas/microbiología , Lesiones Precancerosas/sangre , Factores de Riesgo , PrevalenciaAsunto(s)
Células Epiteliales , Mucosa Gástrica , Infecciones por Helicobacter , Helicobacter pylori , Interleucina-18 , Animales , Ratones , Interleucina-18/metabolismo , Interleucina-18/genética , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiología , Células Epiteliales/metabolismo , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Lesiones Precancerosas/microbiología , Ratones Endogámicos C57BLRESUMEN
Gastric cancer is a malignant tumor with high incidence and death rate. Every year, Approximately 950,000 new cases of gastric cancer occur globally with nearly 700000 deaths,so gastric precancerous lesions(GPL) was crucial and important.At present, the effective diagnostic methods for gastric precancerous lesions are generally gastroscope and pathological changes of gastric mucosal, but those methods were invasive and would bring some pains to patients and not suitable for frequent and large-scale screening of gastric cancer or GPL.This study aimed to look for a sensitive,effective and non-invasive diagnostic method to improve the early diagnosis rate of GLP, and thereby reduce the incidence and death rate of gastric cancer.Tongue diagnosis is one of the classic diagnostic methods in traditional Chinese medicine(TCM).The tongue was closely related to the spleen and stomach.In the study, we collected 133 patients with chronic gastritis, including 53 cases in inflammatory group, 31 cases in atrophic group, and 49 cases in intestinal metaplasia group. and we analyzed the correlation between tongue,microbiota of tongue coating and clinical symptoms of GLP.The results showed that greasy coating was closely related to the intestinal metaphase of patients, indicating that greasy coating was closed link with intestinal metaphase phase of patients.Abundance of 209 genus were significant differences between greasy and non-greasy coating in intestinal metaphase phase of patients, Top10 were Streptococcus,norank_p__Saccharibacteria,Alloprevotella, Atopobium, Megasphaera, Gemella, Moraxella,unclassified_f__Prevotellaceae, Solobacterium and Stomatobaculum. Alloprevotella and Streptococcus were important genus markers and Alloprevotella was selected as a potential oral biomarker to diagnose intestinal metaphase phase of patients, the AUC value is 0.74.
Asunto(s)
Gastritis , Lesiones Precancerosas , Neoplasias Gástricas , Humanos , Gastritis/diagnóstico , Gastritis/microbiología , Gastritis/patología , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , Metafase , Biomarcadores , Lesiones Precancerosas/microbiologíaRESUMEN
Microbial signatures show remarkable potentials in predicting colorectal cancer (CRC). This study aimed to evaluate the diagnostic powers of multimodal microbial signatures, multi-kingdom species, genes, and single-nucleotide variants (SNVs) for detecting precancerous adenomas. We performed cross-cohort analyses on whole metagenome sequencing data of 750 samples via xMarkerFinder to identify adenoma-associated microbial multimodal signatures. Our data revealed that fungal species outperformed species from other kingdoms with an area under the ROC curve (AUC) of 0.71 in distinguishing adenomas from controls. The microbial SNVs, including dark SNVs with synonymous mutations, displayed the strongest diagnostic capability with an AUC value of 0.89, sensitivity of 0.79, specificity of 0.85, and Matthews correlation coefficient (MCC) of 0.74. SNV biomarkers also exhibited outstanding performances in three independent validation cohorts (AUCs = 0.83, 0.82, 0.76; sensitivity = 1.0, 0.72, 0.93; specificity = 0.67, 0.81, 0.67, MCCs = 0.69, 0.83, 0.72) with high disease specificity for adenoma. In further support of the above results, functional analyses revealed more frequent inter-kingdom associations between bacteria and fungi, and abnormalities in quorum sensing, purine and butanoate metabolism in adenoma, which were validated in a newly recruited cohort via qRT-PCR. Therefore, these data extend our understanding of adenoma-associated multimodal alterations in the gut microbiome and provide a rationale of microbial SNVs for the early detection of CRC.
Asunto(s)
Adenoma , Neoplasias Colorrectales , Detección Precoz del Cáncer , Microbioma Gastrointestinal , Polimorfismo de Nucleótido Simple , Lesiones Precancerosas , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/microbiología , Detección Precoz del Cáncer/métodos , Metagenómica , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/microbiología , Adenoma/diagnóstico , Adenoma/microbiología , Metagenoma , Microbioma Gastrointestinal/genética , Marcadores Genéticos , Heces/microbiología , Humanos , Hongos/genética , Hongos/aislamiento & purificación , Bacterias/genética , Bacterias/aislamiento & purificación , Archaea/genética , Archaea/aislamiento & purificación , Virus/genética , Virus/aislamiento & purificación , Estudios de CohortesRESUMEN
Metabolites and their interactions with microbiota may be involved in Helicobacter pylori-associated gastric lesion development. This study aimed to explore metabolite alterations upon H. pylori eradication and possible roles of microbiota-metabolite interactions in progression of precancerous lesions. Targeted metabolomics assays and 16S rRNA gene sequencing were conducted to investigate metabolic and microbial alterations of paired gastric biopsy specimens in 58 subjects with successful and 57 subjects with failed anti-H. pylori treatment. Integrative analyses were performed by combining the metabolomics and microbiome profiles from the same intervention participants. A total of 81 metabolites were significantly altered after successful eradication compared to failed treatment, including acylcarnitines, ceramides, triacylglycerol, cholesterol esters, fatty acid, sphingolipids, glycerophospholipids, and glycosylceramides, with P values of <0.05 for all. The differential metabolites showed significant correlations with microbiota in baseline biopsy specimens, such as negative correlations between Helicobacter and glycerophospholipids, glycosylceramide, and triacylglycerol (P < 0.05 for all), which were altered by eradication. The characteristic negative correlations between glycosylceramides and Fusobacterium, Streptococcus, and Gemella in H. pylori-positive baseline biopsy specimens were further noticed in active gastritis and intestinal metaplasia (P < 0.05 for all). A panel including differential metabolites, genera, and their interactions may help to discriminate high-risk subjects who progressed from mild to advanced precancerous lesions in short-term and long-term follow-up periods with areas under the curve (AUC) of 0.914 and 0.801, respectively. Therefore, our findings provide new insights into the metabolites and microbiota interactions in H. pylori-associated gastric lesion progression. IMPORTANCE In this study, a panel was established including differential metabolites, genera, and their interactions, which may help to discriminate high-risk subjects for progression from mild lesions to advanced precancerous lesions in short-term and long-term follow-up.
Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Microbiota , Lesiones Precancerosas , Neoplasias Gástricas , Humanos , Helicobacter pylori/genética , ARN Ribosómico 16S/genética , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Lesiones Precancerosas/microbiologíaRESUMEN
BACKGROUND: Cervical cancer is the fourth most common malignancy and fourth leading cause of cancer death in women worldwide. More than 99.7% of cases are caused by human papillomavirus (HPV), while HPV types 16 and 18 cause over 70% of all cervical cancer cases. In this preliminary study, we aimed to investigate the presence of HPV infection and diversity of bacteria associated with bacterial vaginosis. METHODS: Cervical swabs (n = 21) taken from women aged 21-47 years, in seventeen cases, with different degrees of cervical abnormality, and from four healthy women, were tested for the presence of HPV DNA, as well as the bacterial strains associated with bacterial vaginosis, using the real-time PCR method. RESULTS: HPV16 was the dominant genotype in 53% (9/17) of patients with confirmed precancerous lesions (ASCUS, LSIL, and HSIL). In specimens with confirmed cytological abnormalities and hrHPV infection, we detected a wide diversity of microbes, while the most common species were Gardnerella vaginalis, Atopobium vaginae, Prevotella bivia, Ureaplasma parvum, Ureaplasma urealyticum, Leptotrichia amnionii, Bacteroides ureolyticus, and Sneathia sanguinegens. The presence of pathogens did not differ, depending on the degree of precancerous lesions or HPV type. CONCLUSION: In our work, HPV16 dominated in patients with cervical precancerous lesions. We also suggest an increased bacterial diversity of the vaginal microbiome in patients with cervical lesions, for which the HPV virus is largely responsible.
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Microbiota , Infecciones por Papillomavirus , Lesiones Precancerosas , Neoplasias del Cuello Uterino , Vaginosis Bacteriana , Humanos , Femenino , Infecciones por Papillomavirus/complicaciones , Vaginosis Bacteriana/microbiología , Cuello del Útero , Papillomaviridae/genética , Papillomavirus Humano 16/genética , Lesiones Precancerosas/microbiologíaRESUMEN
OBJECTIVE: Gastric cancer (GC) is a heterogeneous disease with molecular diversity between and within tumors; therefore, searching for altered genes within this cancer is mandatory to reach the proper individualized targeted therapy. Expressions of Metallothionein (MT) and p21 are not uniform in various types of cancers and their predictive value in GC is controversial. This study aimed to assess the role of MT and p21 in intestinal-type GC and some of its precursor lesions. MATERIALS AND METHODS: Immunohistochemical staining for MT and p21 was applied on paraffin blocks belonging to 30 GCs and 51 benign gastric lesions/precancerous lesions [33 chronic gastritis and 18 chronic gastritis with gastric intestinal metaplasia (GIM)]; 27 of them were associated with H. pylori infection. RESULTS: MT expression was dramatically increased while p21 expression was dramatically decreased from chronic gastritis to GIM to GC. In precancerous lesions, H. pylori-positive cases had significantly higher MT expression and lower p21 expression compared to H. pylori-negative cases. In GCs, decreased expression of both MT and p21 was associated with high-grade and advanced-stage cancers. CONCLUSIONS: Both MT and p21 may have a role in the development and progression of GC, and both proteins may be useful for selecting targeted therapy for GC patients.
Asunto(s)
Metalotioneína , Lesiones Precancerosas , Neoplasias Gástricas , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/biosíntesis , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Gastritis/metabolismo , Gastritis/microbiología , Gastritis/patología , Infecciones por Helicobacter/metabolismo , Infecciones por Helicobacter/patología , Helicobacter pylori/aislamiento & purificación , Humanos , Metalotioneína/biosíntesis , Metalotioneína/genética , Metaplasia/metabolismo , Metaplasia/patología , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/microbiología , Lesiones Precancerosas/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patologíaRESUMEN
We studied the association of expression of CDX2, CK20, CK7 proteins with familial predisposition to stomach cancer in schoolchildren with gastritis and its activity. Gastroscopy with biopsy of the gastric mucosa was performed in 89 schoolchildren aged 7-17 years with gastrointestinal complaints. The morphological study included the diagnosis of gastritis (Sydney classification) and the presence of Helicobacter pylori. The expression of CDX2, CK20, and CK7 was evaluated immunohistochemically. In children with familial predisposition to stomach cancer, the expression of CK20 in the stomach body was significantly increased (p=0.0225). In addition, the expression of CK20 (p=0.0979) and CDX2 (p=0.0849) tended to insrease in the antral compartment. No significant differences in the expression of CK7 in the gastric antrum and body were found. Some features of the expression of CDX2, CK20, and CK7 proteins in children with family predisposition to stomach cancer were revealed.
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Factor de Transcripción CDX2/metabolismo , Gastritis/diagnóstico , Queratina-7/metabolismo , Lesiones Precancerosas/diagnóstico , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/microbiología , Adenocarcinoma/patología , Adolescente , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Niño , Femenino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiología , Gastritis/microbiología , Gastritis/patología , Predisposición Genética a la Enfermedad , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/metabolismo , Helicobacter pylori/fisiología , Humanos , Queratina-20/metabolismo , Masculino , Lesiones Precancerosas/genética , Lesiones Precancerosas/microbiología , Lesiones Precancerosas/patología , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/microbiologíaRESUMEN
BACKGROUND: Gastric intestinal metaplasia (IM) can lead to gastric cancer. Until now, there have been limited studies of predictors for regression and progression of IM. This study aimed to determine risk factors associated with regression or progression of IM for guiding proper management and prevention of gastric cancer. METHODS: 2,025 patients undergoing gastroscopy in Thammasat University Hospital, Thailand were enrolled during September 2017-August 2019. Patients' data including baseline characteristics, laboratory results, and histopathology of gastric biopsies from University medical database were extensively reviewed. RESULTS: 2,025 patients had mean age of 61.3 years and 44.2% were males. Overall H. pylori prevalence was 47.5%. There were 1,551(76.6%) patients with chronic gastritis and 361(17.8%) with IM. Of 400 patients with chronic gastritis having follow-up endoscopy and repeated gastric biopsies, 104(26%) had persistent H. pylori infection and 27(26%) developed IM during mean follow-up time of 24 months. Persistent H. pylori infection was significantly associated with development of IM (OR 3.16, 95%CI 1.56-6.39, p = 0.001). Regression, persistence, and progression of IM were demonstrated in 57.3%, 39.2%, and 3.5% of patients, respectively. Age >65 years, persistent H. pylori infection, and diabetes mellitus were significantly associated with persistent IM or progression to dysplasia with OR 2.47(95%CI 1.33-4.61, p = 0.004), OR 2.64(95%CI 1.13-6.18, p = 0.025), and OR 2.54(95%CI 1.16-5.54, p = 0.019), respectively. Patients without H. pylori infection had more IM regression than patients with persistent infection (60.4%vs.39.4%, p = 0.035). Patients with persistent H. pylori infection significantly had higher IM progression to dysplasia (15.2%vs.2.1%; OR 11.15, 95%CI 1.18-105.24, p = 0.035) than noninfected. During 24 months of study, 30 patients (1.5%) were diagnosed with gastric cancer. CONCLUSION: Regression of IM could be achieved by successful H. pylori eradication. Persistent H. pylori infection was significantly associated with development and progression of IM to dysplasia. Age >65 years and diabetes mellitus were also significant predictors for IM progression.
Asunto(s)
Gastritis Atrófica/patología , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/aislamiento & purificación , Metaplasia/patología , Lesiones Precancerosas/patología , Neoplasias Gástricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Gastritis Atrófica/epidemiología , Gastritis Atrófica/microbiología , Infecciones por Helicobacter/microbiología , Humanos , Masculino , Metaplasia/epidemiología , Metaplasia/microbiología , Persona de Mediana Edad , Lesiones Precancerosas/epidemiología , Lesiones Precancerosas/microbiología , Prevalencia , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/microbiología , Tailandia/epidemiología , Adulto JovenRESUMEN
Background: Cytokines and their gene variants are proven to play a role in pathogenic gastritis and carcinogenesis. The study assesses associations of the cytokine gene polymorphisms with extension of atrophic gastritis/intestinal metaplasia (AGIM) in patients without Helicobacter pylori infection on immunohistochemistry study. Methods: 224 adult consecutive patients undergoing an upper digestive endoscopy were included and grouped according to localization of AGIM: 37 patients with antrum-limited AGIM, 21 corpus-limited AGIM, 15 extended-AGIM (antrum and corpus) and 151 patients had no AGIM. Medical records of the patients were checked and a structured direct interview was applied in order to collect clinical data, including digestive symptoms. In all cases, IFN-γ +874T>A, TGF-ß1 +869T>C, TNF-α-308G>A and -238G>A, and IL-6 -174C>G polymorphisms were genotyped. Results: The mean age was significantly higher in the AGIM group, while the comorbidies were similar among patients with different localization of lesions or in patients without AGIM. There were no significant differences in digestive symptoms, nor in the consumption of non-steroidal anti-inflammatory drugs or proton pump inhibitor with the different extensions of AGIM. There was a significant association between oral anticoagulant consumption and localization of AGIM (P = 0.042), frequency being higher among patients with corpus-limited AGIM than those with no AGIM (P = 0.007, adjusted P = 0.041). TGF-ß1 +869T>C was less frequent among patients with corpus-limited AGIM (n=7, 33.3%) and extended AGIM (n=5, 33.3%) than in antrum-limited AGIM (n=25, 67.6%). There were no other significant differences regarding variant and wild genotype frequencies of IFN-γ +874T>A (86.5%, 81.0%, 86.7%, p=0.814), TNF-α-308G>A (35.1%, 28.6%, 53.3%, p=0.48) and IL-6 -174C>G (70.3%. 61.9%, 73.3% p=0.656) among patients with antrum-limited, corpus-limited or extended AGIM. TGF-ß1 +869T>C was associated with a decreased risk for corpus-affected AGIM (adjusted odds ratio: 0.42, 95% confidence interval: 0.19-0.93, P = 0.032). The dominant inheritance models no revealed significant association for IFN-γ +874T>A, TNF-α-308G>A and IL-6 -174C>G gene polymorphism and the risk of localization of AGIM. Conclusion: TGF-ß1 +869T>C gene polymorphism is associated with a decreased risk for corporeal localization of premalignant lesions, while IFN-γ +874T>A, TNF-α-308G>A and IL-6 -174C>G are not associated with the risk for AGIM in immunohistochemically H. pylori negative patients.
Asunto(s)
Mucosa Gástrica/patología , Gastritis Atrófica/epidemiología , Predisposición Genética a la Enfermedad , Lesiones Precancerosas/epidemiología , Factor de Crecimiento Transformador beta1/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Biopsia , Femenino , Mucosa Gástrica/microbiología , Gastritis Atrófica/genética , Gastritis Atrófica/microbiología , Gastritis Atrófica/patología , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/aislamiento & purificación , Humanos , Inmunohistoquímica , Interferón gamma/genética , Interleucina-6/genética , Masculino , Metaplasia/epidemiología , Metaplasia/genética , Metaplasia/microbiología , Metaplasia/patología , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Lesiones Precancerosas/genética , Lesiones Precancerosas/microbiología , Lesiones Precancerosas/patología , Factores Protectores , Medición de Riesgo/estadística & datos numéricos , Factor de Necrosis Tumoral alfa/genética , Adulto JovenRESUMEN
BACKGROUND: In corpus atrophic gastritis (CAG), hypochlorhydria makes plausible the overgrowth of intragastric bacteria, whose role in gastric carcinogenesis is under debate. AIMS: To characterize the antrum/corpus composition of the gastric bacterial microbiota in CAG patients compared to controls without CAG. METHODS: A cross-sectional monocentric study on consecutive patients with known histological diagnosis of CAG undergoing gastroscopy for gastric cancer surveillance and patients without CAG undergoing gastroscopy for dyspepsia or anemia (108 biopsies from 55 patients, median age 61.5). Genomic DNA from one antral and one corpus biopsy from each case (nâ¯=â¯23) and control (nâ¯=â¯32) was extracted. Gastric microbiota was assessed by sequencing hypervariable regions of the 16SrRNA gene. RESULTS: Bacterial abundance and diversity were significantly lower in CAG cases than in controls (p < 0.001). Firmicutes were more frequent in cases, Bacteroidetes and Fusobacteria in controls (p < 0.0001). Streptococcaceae were more abundant in cases (p < 0.0001), Prevotellaceae in controls (p < 0.0001). The genus Streptococcus was positively correlated with severe OLGA/OLGIM stages linked to a higher risk of gastric cancer. CONCLUSION: Gastric bacterial microbiota in CAG showed a reduced abundance and complexity but was characterized by higher colonization of Firmicutes, in particular Streptococcus, increased in subjects with severe atrophy/metaplasia stages at higher risk of gastric cancer.
Asunto(s)
Gastritis Atrófica/microbiología , Microbioma Gastrointestinal , Aclorhidria/metabolismo , Aclorhidria/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Estudios Transversales , Femenino , Firmicutes/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Lesiones Precancerosas/microbiología , Lesiones Precancerosas/patología , Medición de Riesgo , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patologíaRESUMEN
There is increasing evidence showing positive association between changes in oral microbiome and the occurrence of oral squamous cell carcinoma (OSCC). Alcohol- and nicotine-related products can induce microbial changes but are still unknown if these changes are related to cancerous lesion sites. In an attempt to understand how these changes can influence the OSCC development and maintenance, the aim of this study was to investigate the oral microbiome linked with OSCC as well as to identify functional signatures and associate them with healthy or precancerous and cancerous sites. Our group used data of oral microbiomes available in public repositories. The analysis included data of oral microbiomes from electronic cigarette users, alcohol consumers, and precancerous and OSCC samples. An R-based pipeline was used for taxonomic and functional prediction analysis. The Streptococcus spp. genus was the main class identified in the healthy group. Haemophilus spp. predominated in precancerous lesions. OSCC samples revealed a higher relative abundance compared with the other groups, represented by an increased proportion of Fusobacterium spp., Prevotella spp., Haemophilus spp., and Campylobacter spp. Venn diagram analysis showed 52 genera exclusive of OSCC samples. Both precancerous and OSCC samples seemed to present a specific associated functional pattern. They were menaquinone-dependent protoporphyrinogen oxidase pattern enhanced in the former and both 3',5'-cyclic-nucleotide phosphodiesterase (purine metabolism) and iron(III) transport system ATP-binding protein enhanced in the latter. We conclude that although precancerous and OSCC samples present some differences on microbial profile, both microbiomes act as "iron chelators-like" potentially contributing to tumor growth.
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Carcinoma de Células Escamosas , Hierro/metabolismo , Microbiota , Neoplasias de la Boca , Microambiente Tumoral , Consumo de Bebidas Alcohólicas , Carcinoma de Células Escamosas/microbiología , Sistemas Electrónicos de Liberación de Nicotina , Compuestos Férricos/metabolismo , Humanos , Neoplasias de la Boca/microbiología , Lesiones Precancerosas/microbiologíaRESUMEN
ABSTRACT: Epidermal barrier disruption caused by atypical squamous proliferations of the lip (SOL) creates an ideal environment for fungal growth. Histologic features of SOL include parakeratosis overlying partial- or full-thickness keratinocyte atypia with or without invasion of the dermis, dermal solar elastosis, and scattered inflammatory cells which are predominantly lymphocytes. Histologic features of SOL with fungal superinfections overlap those seen in primary fungal cheilitis with reactive atypia, creating a diagnostic challenge. One-hundred seventy SOL cases were examined for the presence of fungal elements, and the histological features associated with superinfection were identified. Cases diagnosed as actinic cheilitis with fungal superinfection were carefully examined to rule out the possibility of misdiagnosed primary fungal cheilitis with reactive atypia. Histopathological characteristics commonly present with fungal hyphae included intraepidermal or intradermal neutrophils, bacterial colonies, and erosion or ulceration. Medical record review of those patients treated conservatively with topical antifungals revealed persistent clinical neoplasm and histological evidence of residual SOL on repeat biopsy. Thus, when biopsies exhibit histological overlap between these 2 entities, clinicians should keep a high index of suspicion for underlying SOL and carefully follow these patients if conservative antifungal therapy is initially trialed.
Asunto(s)
Proliferación Celular , Queilitis/patología , Hongos/patogenicidad , Hifa/patogenicidad , Neoplasias de los Labios/patología , Micosis/patología , Lesiones Precancerosas/patología , Adulto , Anciano , Anciano de 80 o más Años , Antifúngicos/uso terapéutico , Biopsia , Queilitis/tratamiento farmacológico , Queilitis/microbiología , Diagnóstico Diferencial , Femenino , Hongos/aislamiento & purificación , Interacciones Huésped-Patógeno , Humanos , Hifa/aislamiento & purificación , Neoplasias de los Labios/tratamiento farmacológico , Neoplasias de los Labios/microbiología , Masculino , Persona de Mediana Edad , Micosis/tratamiento farmacológico , Micosis/microbiología , Lesiones Precancerosas/tratamiento farmacológico , Lesiones Precancerosas/microbiología , Valor Predictivo de las Pruebas , Resultado del TratamientoRESUMEN
BACKGROUND: How gastric cancer (GC) incidence is associated with changes in the gastric microbiome has not been firmly established. The present study therefore aims to investigate the microbial communities present within the gastric mucosa of patients with superficial gastritis (SG) or GC. METHODS: Paired tumor and paracancerous samples of the gastric mucosa were collected from 18 patients being surgically treated for GC and from 32 patients with SG being treated via gastroscopy. The gastric microbiome in these samples was then profiled via 16S rRNA sequencing, with a linear discriminant analysis effect size (LEfSe) approach used to identify and compare different bacteria, and with PICRUSt used for predictive functional analyses. RESULTS: GC patients exhibited a distinct gastric microbiota profile from that observed in SG patients. These changes were evident in both tumor and paracancerous tissues from GC patients. Specifically, we found that 6 bacterial genera were specifically enriched in GC tissue samples relative to SG samples, while 18 genera were depleted in these same samples. Based on the differential abundance of these bacteria, we were able to calculate microbial dysbiosis index (MDI) values, which were significantly higher in GC patients than in SG patients. In addition, MDI values were negatively correlated with gastric Shannon index and were positively correlated with relative Helicobacter spp. abundance. Importantly, these MDI values were readily able to discriminate between GC and SG patient samples. Functional analysis suggested that GC patients were more likely to harbor a nitrosating microbial community. CONCLUSIONS: GC patients exhibited a gastric microbiome profile distinct from that observed in SG patients, with these differences being evident in both tumor and paracancerous tissues. Differences in the relative abundance of Helicobacter spp. may be the primary driver of gastric dysbiosis in GC patients.
Asunto(s)
Bacterias/aislamiento & purificación , Mucosa Gástrica/microbiología , Gastritis/microbiología , Microbioma Gastrointestinal , Lesiones Precancerosas/microbiología , Neoplasias Gástricas/microbiología , Anciano , Bacterias/genética , Biopsia , Disbiosis , Femenino , Gastrectomía , Mucosa Gástrica/patología , Mucosa Gástrica/cirugía , Gastritis/patología , Gastritis/cirugía , Gastroscopía , Humanos , Masculino , Persona de Mediana Edad , Lesiones Precancerosas/patología , Lesiones Precancerosas/cirugía , Ribotipificación , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugíaRESUMEN
BACKGROUND & AIMS: Inflammation in the gastrointestinal tract may lead to the development of cancer. Dicarbonyl electrophiles, such as isolevuglandins (isoLGs), are generated from lipid peroxidation during the inflammatory response and form covalent adducts with amine-containing macromolecules. Thus, we sought to determine the role of dicarbonyl electrophiles in inflammation-associated carcinogenesis. METHODS: The formation of isoLG adducts was analyzed in the gastric tissues of patients infected with Helicobacter pylori from gastritis to precancerous intestinal metaplasia, in human gastric organoids, and in patients with colitis and colitis-associated carcinoma (CAC). The effect on cancer development of a potent scavenger of dicarbonyl electrophiles, 5-ethyl-2-hydroxybenzylamine (EtHOBA), was determined in transgenic FVB/N insulin-gastrin (INS-GAS) mice and Mongolian gerbils as models of H pylori-induced carcinogenesis and in C57BL/6 mice treated with azoxymethane-dextran sulfate sodium as a model of CAC. The effect of EtHOBA on mutations in gastric epithelial cells of H pylori-infected INS-GAS mice was assessed by whole-exome sequencing. RESULTS: We show increased isoLG adducts in gastric epithelial cell nuclei in patients with gastritis and intestinal metaplasia and in human gastric organoids infected with H pylori. EtHOBA inhibited gastric carcinoma in infected INS-GAS mice and gerbils and attenuated isoLG adducts, DNA damage, and somatic mutation frequency. Additionally, isoLG adducts were elevated in tissues from patients with colitis, colitis-associated dysplasia, and CAC as well as in dysplastic tumors of C57BL/6 mice treated with azoxymethane-dextran sulfate sodium. In this model, EtHOBA significantly reduced adduct formation, tumorigenesis, and dysplasia severity. CONCLUSIONS: Dicarbonyl electrophiles represent a link between inflammation and somatic genomic alterations and are thus key targets for cancer chemoprevention.