RESUMO
Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide because of its high morbidity and the absence of effective therapies. Even though paclitaxel is a powerful anticancer chemotherapy drug, recent studies have indicated its ineffectiveness against GC cells. Long non-coding RNA (lncRNA) PVT1 has a high expression in GC cells and increases the progression of tumors via inducing drug resistance. In the present study, the effects of the siRNA-mediated lncRNA PVT1 gene silencing along with paclitaxel treatment on the rate of apoptosis, growth, and migration of AGS GC cells were investigated. AGS cells were cultured and then transfected with siRNA PVT1 using electroporation. The MTT test was used to examine the effect of treatments on the viability of cultured cells. Furthermore, the flow cytometry method was used to evaluate the impact of treatments on the cell cycle process and apoptosis induction in GC cells. Finally, the mRNA expression of target genes was assessed using the qRT-PCR method. The results showed that lncRNA PVT1 gene suppression, along with paclitaxel treatment, reduces the viability of cancer cells and significantly increases the apoptosis rate of cancer cells and the number of cells arrested in the G2/M phase compared to the control group. Based on the results of qRT-PCR, combined treatment significantly decreased the expression of MMP3, MMP9, MDR1, MRP1, Bcl-2, k-Ras, and c-Myc genes and increased the expression of the Bax gene compared to the control group. The results of our study showed that lncRNA PVT1 gene targeting, together with paclitaxel treatment, induces apoptosis, inhibits growth, alleviates drug resistance, and reduces the migratory capability of GC cells. Therefore, there is a need for further investigations to evaluate the feasibility and effectiveness of this approach in vivo in animal models.
Assuntos
Apoptose , Resistencia a Medicamentos Antineoplásicos , Inativação Gênica , Paclitaxel , RNA Longo não Codificante , Neoplasias Gástricas , RNA Longo não Codificante/genética , Paclitaxel/farmacologia , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Apoptose/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , RNA Interferente Pequeno/genéticaRESUMO
Early diagnosis and treatment of gastric cancer (GC) play a vital role in improving efficacy, reducing mortality and prolonging patients' lives. Given the importance of early detection of gastric cancer, an electrochemical biosensor was developed for the ultrasensitive detection of miR-19b-3p by integrating MoS2-based nanozymes, hybridization chain reaction (HCR) with enzyme catalyzed reaction. The as-prepared MoS2-based nanocomposites were used as substrate materials to construct nanoprobes, which can simultaneously load probe DNA and HCR initiator for signal amplification. Moreover, the MoS2-based nanocomposites are also employed as nanozymes to amplify electrochemical response. The presence of miR-19b-3p induced the assembly of MoS2-based nanoprobes on the electrode surface, which can activate in-situ HCR reaction to load a large number of horseradish peroxidase (HRP) for signal amplification. Coupling with the co-catalytic ability of HRP and MoS2-based nanozymes, the designed electrochemical biosensor can detect as low as 0.7 aM miR-19b-3p. More importantly, this biosensor can efficiently analyze miR-19b-3p in clinical samples from healthy people and gastric cancer patients due to its excellent sensitivity and selectivity, suggesting that this biosensor has a potential application in early diagnosis of disease.
Assuntos
Técnicas Biossensoriais , Dissulfetos , Técnicas Eletroquímicas , Peroxidase do Rábano Silvestre , MicroRNAs , Molibdênio , Neoplasias Gástricas , Neoplasias Gástricas/diagnóstico , Humanos , MicroRNAs/genética , Molibdênio/química , Técnicas Eletroquímicas/métodos , Peroxidase do Rábano Silvestre/química , Peroxidase do Rábano Silvestre/metabolismo , Técnicas Biossensoriais/métodos , Dissulfetos/química , Hibridização de Ácido Nucleico , Nanocompostos/química , Limite de DetecçãoRESUMO
PURPOSE: DNA methylation prominently inactivates tumor suppressor genes and facilitates oncogenesis. Previously, we delineated a chromosome 18 deletion encompassing the erythrocyte membrane protein band 4.1-like 3 (EPB41L3) gene, a progenitor for the tumor suppressor that is differentially expressed in adenocarcinoma of the lung-1 (DAL-1) in gastric cancer (GC). METHODS: Our current investigation aimed to elucidate EPB41L3 expression and methylation in GC, identify regulatory transcription factors, and identify affected downstream pathways. Immunohistochemistry demonstrated that DAL-1 expression is markedly reduced in GC tissues, with its downregulation serving as an independent prognostic marker. RESULTS: High-throughput bisulfite sequencing of 70 GC patient tissue pairs revealed that higher methylation of non-CpGs in the EPB41L3 promoter was correlated with more malignant tumor progression and higher-grade tissue classification. Such hypermethylation was shown to diminish DAL-1 expression, thus contributing to the malignancy of GC phenotypes. The DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) was found to partially restore DAL-1 expression. Moreover, direct binding of the transcription factor CDC5L to the upstream region of the EPB41L3 promoter was identified via chromosome immunoprecipitation (ChIP)-qPCR and luciferase reporter assays. Immunohistochemistry confirmed the positive correlation between CDC5L and DAL-1 protein levels. Subsequent RNA-seq analysis revealed that DAL-1 significantly influences the extracellular matrix and space-related pathways. GC cell RNA-seq post-5-Aza-CdR treatment and single-cell RNA-seq data of GC tissues confirmed the upregulation of AREG and COL17A1, pivotal tumor suppressors, in response to EPB41L3 demethylation or overexpression in GC epithelial cells. CONCLUSION: In conclusion, this study elucidates the association between non-CpG methylation of EPB41L3 and GC progression and identifies the key transcription factors and downstream molecules involved. These findings enhance our understanding of the role of EPB41L3 in gastric cancer and provide a solid theoretical foundation for future research and potential clinical applications.
The EPB41L3 gene, frequently exhibiting haplotype deletions and reduced expression in gastric cancer tissues, points to its potential role as a tumor suppressor. However, tumor suppressor genes are not only influenced by genomic deletions but also by their methylation status. Our study highlights the significantly lower expression of EPB41L3 in gastric cancer compared to adjacent non-cancerous tissues across 262 patients. We also discovered that elevated non-CpG island methylation of EPB41L3 correlates strongly with tumor malignancy progression, based on the analysis of 70 paired gastric cancer samples. Moreover, we identified CDC5L as a crucial transcription factor interacting with the EPB41L3 promoter. Integrative analyses of transcriptomic and single-cell sequencing data further revealed that AREG and COL17A1 are key downstream molecules regulated by DAL-1, with their expression tightly controlled by EPB41L3 methylation and expression levels. These insights enhance our understanding of EPB41L3's role in gastric cancer and could open new avenues for targeted therapies.
Assuntos
Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Regiões Promotoras Genéticas , Neoplasias Gástricas , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Humanos , Metilação de DNA/genética , Feminino , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , Linhagem Celular Tumoral , Idoso , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas dos MicrofilamentosRESUMO
Background: The relationship between dysbiosis of the gastrointestinal microbiota and gastric cancer (GC) has been extensively studied. However, microbiota alterations in GC patients vary widely across studies, and reproducible diagnostic biomarkers for early GC are still lacking in multiple populations. Thus, this study aimed to characterize the gastrointestinal microbial communities involved in gastric carcinogenesis through a meta-analysis of multiple published and open datasets. Methods: We analyzed 16S rRNA sequencing data from 1,642 gastric biopsy samples and 394 stool samples across 11 independent studies. VSEARCH, QIIME and R packages such as vegan, phyloseq, cooccur, and random forest were used for data processing and analysis. PICRUSt software was employed to predict functions. Results: The α-diversity results indicated significant differences in the intratumoral microbiota of cancer patients compared to non-cancer patients, while no significant differences were observed in the fecal microbiota. Network analysis showed that the positive correlation with GC-enriched bacteria increased, and the positive correlation with GC-depleted bacteria decreased compared to healthy individuals. Functional analyses indicated that pathways related to carbohydrate metabolism were significantly enriched in GC, while biosynthesis of unsaturated fatty acids was diminished. Additionally, we investigated non-Helicobacter pylori (HP) commensals, which are crucial in both HP-negative and HP-positive GC. Random forest models, constructed using specific taxa associated with GC identified from the LEfSe analysis, revealed that the combination of Lactobacillus and Streptococcus included alone could effectively discriminate between GC patients and healthy individuals in fecal samples (area under the curve (AUC) = 0.7949). This finding was also validated in an independent cohort (AUC = 0.7712). Conclusions: This study examined the intratumoral and fecal microbiota of GC patients from a dual microecological perspective and identified Lactobacillus, Streptococcus, Roseburia, Faecalibacterium and Phascolarctobacterium as intratumoral and intestinal-specific co-differential bacteria. Furthermore, it confirmed the validity of the combination of Lactobacillus and Streptococcus as GC-specific microbial markers across multiple populations, which may aid in the early non-invasive diagnosis of GC.
Assuntos
Fezes , Microbioma Gastrointestinal , RNA Ribossômico 16S , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/microbiologia , Fezes/microbiologia , Microbioma Gastrointestinal/genética , RNA Ribossômico 16S/genética , Disbiose/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , CarcinogêneseRESUMO
BACKGROUND: Queiroz et al. showed that the application of cluster methodology for classifying gastric cancer is suitable and efficient within a Brazilian cohort, which is known for its population heterogeneity. The study highlighted the potential utilization of this method within public health services due to its low-cost, presenting a viable means to improve the diagnosis and prognosis of gastric cancer. BACKGROUND: Our Brazilian cohort with gastric cancer has a distinct distribution between mutated and normal p53. BACKGROUND: New genetic marker-based classifications improve gastric cancer diagnosis accuracy. BACKGROUND: Machine learning integration enhances predictive value in gastric cancer diagnosis. BACKGROUND: Molecular biomarkers complement clinical decisions, advancing personalized medicine. OBJECTIVE: Gastric adenocarcinoma remains an aggressive disease with a poor prognosis, as evidenced by a 5-year survival rate of approximately 31%. The histological classifications already proposed do not accurately reflect the high biological heterogeneity of this neoplasm, particularly in diverse populations, and new classification systems using genetic markers have recently been proposed. Following these newly proposed models, we aimed to assess the cluster distribution in a Brazilian cohort. Furthermore, we evaluated whether the inclusion of other clinical and histological parameters could enhance the predictive value. METHODS: We used a previously described four-immunohistochemistry/EBER-ISH marker to classify a cohort of 30 Brazilian patients with gastric adenocarcinoma into five different clusters and compared the distribution with other genetically diverse populations. Furthermore, we used artificial intelligence methods to evaluate whether other clinical and pathological parameters could improve the results of the methodology. RESULTS: Disclosing the genetic variability between populations, we observed a more balanced distribution of the aberrant/normal p53 ratio (0.6) between patients negative for the other markers tested, unlike previous studies with Asian and North American populations. In addition, decision tree analysis reinforced the efficiency of these new classifications, as the stratification accuracy was not altered with or without additional data. CONCLUSION: Our study underscores the importance of local research in characterizing diverse populations and highlights the complementary role of molecular biomarkers in personalized medicine for gastric adenocarcinoma, enhancing diagnostic accuracy and potentially improving survival rates.
Assuntos
Adenocarcinoma , Biomarcadores Tumorais , Neoplasias Gástricas , Proteína Supressora de Tumor p53 , Neoplasias Gástricas/genética , Neoplasias Gástricas/classificação , Neoplasias Gástricas/patologia , Humanos , Brasil , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/análise , Masculino , Feminino , Adenocarcinoma/genética , Adenocarcinoma/classificação , Adenocarcinoma/patologia , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Estudos de Coortes , Idoso , Análise por Conglomerados , Mutação , Imuno-Histoquímica , Adulto , Prognóstico , Idoso de 80 Anos ou maisAssuntos
Gastrectomia , Laparoscopia , Pontuação de Propensão , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Gastrectomia/métodos , Laparoscopia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento , Metanálise como AssuntoRESUMO
Gastric cancer (GC) remains a significant health challenge due to its high mortality rate and the limited efficacy of current targeted therapies. A critical barrier in developing more effective treatments is the lack of understanding of specific mechanisms driving GC progression. This study investigates the role of Transient Receptor Potential Vanilloid 1 (TRPV1), a non-selective cation channel known for its high Ca2+ permeability and tumor-suppressive properties in gastrointestinal cancers. Specifically, we explore the impact of SUMOylation-a dynamic and reversible post-translational modification-on TRPV1's function in GC. We demonstrate that SUMOylation of TRPV1 inhibits cell proliferation and migration in MGC-803 and AGS GC cells. By mutating amino acids near TRPV1's existing SUMO motif (slKpE), we created a bidirectional SUMO motif (EψKψE) that enhances TRPV1 SUMOylation, resulting in further suppression of GC cell proliferation and migration. In vivo studies support these findings, showing that TRPV1 SUMOylation prevents spontaneous tumorigenesis in a mouse GC model. Further investigation reveals that TRPV1 SUMOylation increases the protein's membrane expression by inhibiting its interaction with the adaptor-related protein complex 2 mu 1 subunit (AP2M1). This elevated membrane expression leads to increased intracellular Ca2+ influx, activating the AMP-activated protein kinase (AMPK) pathway, which in turn inhibits the proliferation and migration of GC cells.
Assuntos
Movimento Celular , Proliferação de Células , Neoplasias Gástricas , Sumoilação , Canais de Cátion TRPV , Canais de Cátion TRPV/metabolismo , Canais de Cátion TRPV/genética , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Animais , Linhagem Celular Tumoral , Camundongos , Membrana Celular/metabolismoRESUMO
Fusobacterium nucleatum (F. nucleatum) is a Gram-negative anaerobic bacterium that plays a key role in the development of oral inflammation, such as periodontitis and gingivitis. In the last 10 years, F. nucleatum has been identified as a prevalent bacterium associated with colorectal adenocarcinoma and has also been linked to cancer progression, metastasis and poor disease outcome. While the role of F. nucleatum in colon carcinogenesis has been intensively studied, its role in gastric carcinogenesis is still poorly understood. Although Helicobacter pylori infection has historically been recognized as the strongest risk factor for the development of gastric cancer (GC), with recent advances in DNA sequencing technology, other members of the gastric microbial community, and F. nucleatum in particular, have received increasing attention. In this review, we summarize the existing knowledge on the involvement of F. nucleatum in gastric carcinogenesis and address the potential translational and clinical significance of F. nucleatum in GC.
Assuntos
Carcinogênese , Infecções por Fusobacterium , Fusobacterium nucleatum , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Fusobacterium nucleatum/patogenicidade , Infecções por Fusobacterium/microbiologia , Infecções por Fusobacterium/complicações , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/complicações , Helicobacter pylori/patogenicidade , Helicobacter pylori/genética , Fatores de Risco , Microbioma Gastrointestinal , Animais , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Estômago/microbiologia , Estômago/patologia , Adenocarcinoma/microbiologia , Adenocarcinoma/patologiaRESUMO
Bibliometric analyses are increasing in the field of gastric cancer. This letter discusses a recently published analysis that focused on the bidirectional relationship between depression and gastric cancer and evaluated the types of papers published in this field and the changes in the direction of research. There is an increasing need for new, clinically relevant studies of this association.
Assuntos
Bibliometria , Depressão , Neoplasias Gástricas , Neoplasias Gástricas/psicologia , Neoplasias Gástricas/patologia , Humanos , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/psicologia , Pesquisa Biomédica/tendências , Pesquisa Biomédica/estatística & dados numéricosRESUMO
New biomarkers for early diagnosis of gastric cancer (GC), the second leading cause of cancer-related death, are urgently needed. IGFBP7, known to play various roles in multiple tumours, is complexly regulated across diverse cancer types, as evidenced by our pancancer analysis. Bioinformatics analysis revealed that IGFBP7 expression was related to patient prognosis, tumour clinicopathological characteristics, tumour stemness, microsatellite instability and immune cell infiltration, as well as the expression of oncogenes and immune checkpoints. GSEA links IGFBP7 to several cancer-related pathways. IGFBP7 deficiency inhibited GC cell proliferation and migration in vitro. Furthermore, an in vivo nude mouse model revealed that IGFBP7 downregulation suppressed the tumorigenesis of GC cells. Western blotting analysis showed that the JAK1/2-specific inhibitor ruxolitinib could rescue alterations induced by IGFBP7 overexpression in GC cells. Additionally, our bioinformatics analysis and in vitro assays suggested that IGFBP7 is regulated by DNA methylation at the genetic level and that the RNA m6A demethylase FTO modulates it at the posttranscriptional level. This study emphasizes the clinical relevance of IGFBP7 in GC and its influence on cell proliferation and migration via the JAK/STAT signalling pathway. This study also highlights the regulation of IGFBP7 in GC by DNA and m6A RNA methylation.
Assuntos
Movimento Celular , Proliferação de Células , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina , Fatores de Transcrição STAT , Transdução de Sinais , Neoplasias Gástricas , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , Movimento Celular/genética , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Animais , Camundongos , Linhagem Celular Tumoral , Fatores de Transcrição STAT/metabolismo , Camundongos Nus , Janus Quinases/metabolismo , Feminino , Masculino , Metilação de RNARESUMO
BACKGROUND: Gastric cancer (GC) is the fourth leading cause of cancer mortality worldwide. Peritoneal metastasis (PM) is a significant cause of death in patients with GC, and presents a major challenge in clinical diagnosis and treatment. Predicting the occurrence of PM in high-risk patients, and diagnosing and treating PM in advance to improve patient survival, remains an unsolved problem in clinical practice. Given the low positive rate of cytology and difficulty in diagnosing occult PM, new molecular markers and detection technologies for early diagnosis require urgent validation. The primary objective of this study is to observe and evaluate the predictive effect of intraoperative peritoneal lavage fluid (PLF) circulating tumour cells (CTC) and circulating tumour DNA (ctDNA) levels in patients with pT4NxM0/pT1-3N+M0 GC on metachronous PM after R0 resection. METHODS AND ANALYSIS: This prospective single-centre clinical study is conducted at Renji Hospital, Shanghai Jiao Tong University School of Medicine. In this study, 200 cases of patients with pT4NxM0/pT1-3N+M0 gastric adenocarcinoma older than 18 years will be screened. Participants will undergo intraoperative PLF CTC and ctDNA testing and will be followed up for 2 years, with imaging assessments performed every 3-6 months until PM occurrs. The primary outcome is the incidence of PM 1 year after surgery, which will be estimated using Clopper-Pearson method, with 95% CIs calculated and compared between groups. Secondary outcome include the incidence of PM 2 years after surgery, overall survival and disease progression. Data will be analysed using the Kaplan-Meier method and the log-rank test. ETHICS AND COMMUNICATION: Informed consent has been obtained from all subjects. This protocol has been approved by the Ethics Committee of Renji Hospital, Shanghai Jiao Tong University School of Medicine (LY2023-142-B). The findings will be disseminated through peer-reviewed manuscripts, reports and presentations. TRIAL REGISTRATION NUMBER: ChiCTR2300074910.
Assuntos
DNA Tumoral Circulante , Células Neoplásicas Circulantes , Lavagem Peritoneal , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgia , Estudos Prospectivos , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/genética , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Masculino , Feminino , Líquido Ascítico/metabolismo , China , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Adenocarcinoma/cirurgia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Valor Preditivo dos Testes , Gastrectomia/métodos , Estadiamento de NeoplasiasRESUMO
BACKGROUND: Adenocarcinoma of the esophagogastric junction (AEGJ) is most common in men and the elderly, but the disease is becoming more common in female and young adult persons. We have investigated the clinicoepidemiological characteristics of female and young adult patients with AEGJ and the 12-year trends in the Kurashiki area for young adult patients with AEGJ. METHODS: Patients diagnosed with AEGJ in 12 hospitals between January 2008 and December 2019 were included in this study. Patients were divided into three groups by age (young adult [≤50 years], middle-aged [51 to 70 years], and elderly [>70 years]). Factors associated with AEGJ such as obesity, smoking, hiatal hernia and male, which were reported in our previous study, were identified. RESULTS: One hundred and eighty-eight AEGJ patients, including 36 females and 20 young adults, were characterized. There was no significant change in the annual incidence of AEGJ among female (p=0.078) and young adult patients (p=0.89). Female patients without any associated factors, accounting for 53% (19/36) of the female patients and young adult patients, had significantly more histologically undifferentiated cancers than patients with at least one associated factor (58% [11/19] vs. 30% [50/169], p=0.025) and middle-aged and elderly patients (60% [12/20] vs. 30% [25/83] vs. 28% [24/85], p =0.026). Smoking was significantly less common in women than in men (8% [3/36] vs. 57% [87/152], p < 0.01). There were no significant differences between ages in the proportions of these associated factors. CONCLUSIONS: Histologically undifferentiated AEGJ cancers were more frequent in female patients without any associated factors and in young adult patients. Factors associated with AEGJ may differ between women and men, but they are similar in young adults and older adults. No increase in young adult patients with AEGJ was observed in the 12-year study.
Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Junção Esofagogástrica , Humanos , Feminino , Junção Esofagogástrica/patologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Idoso , Adulto , Estudos Retrospectivos , Estudos Prospectivos , Incidência , Fatores de Risco , Fatores Sexuais , Fatores Etários , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Fumar/epidemiologia , Adulto Jovem , Hérnia Hiatal/epidemiologiaRESUMO
Gastric cancer is one of the most prevalent tumors in China and other countries, with high morbidity and mortality. Fear of cancer recurrence is common among cancer survivors. Fear of cancer recurrence experiences and psychological interventions have been investigated in breast and other cancers. However, this phenomenon and associated factors have not been evaluated in early gastric cancer survivors in China. The objective of this study was to investigate the nature of fear of cancer recurrence and influencing factors in Chinese patients with early gastric cancer treated with endoscopic submucosal dissection. This cross-sectional study in two centers included 312 early gastric cancer patients who answered self-report questionnaires and were treated with endoscopic submucosal dissection between June 2022 and May 2023 to assess fear of cancer recurrence. Gender, family history of gastrointestinal tumor, tumor recurrence, Helicobacter pylori infection, disease perception, and self-perceived burden were significant factors influencing fear of cancer recurrence (p < .05). More than half of early gastric cancer patients have fear of cancer recurrence, and how to deal with it has become a key issue in the postoperative care of patients. Medical professionals should address these factors to reduce fear of cancer recurrence in at-risk patients.
Assuntos
Ressecção Endoscópica de Mucosa , Medo , Recidiva Local de Neoplasia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/psicologia , Estudos Transversais , Masculino , Feminino , Recidiva Local de Neoplasia/psicologia , Pessoa de Meia-Idade , Idoso , China , Inquéritos e Questionários , AdultoRESUMO
The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Na Li, Mei Han, Ning Zhou, Yong Tang, Xu-Shan Tang. MicroRNA-495 Confers Increased Sensitivity to Chemotherapeutic Agents in Gastric Cancer via the Mammalian Target of Rapamycin (mTOR) Signaling Pathway by Interacting with Human Epidermal Growth Factor Receptor 2 (ERBB2). Med Sci Monit, 2018; 24: CLR5990-5972. DOI: 10.12659/MSM.909458.
Assuntos
Antineoplásicos , MicroRNAs , Receptor ErbB-2 , Transdução de Sinais , Neoplasias Gástricas , Serina-Treonina Quinases TOR , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genéticaRESUMO
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.
Assuntos
Doenças Autoimunes , Bibliometria , Mucosa Gástrica , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Lesões Pré-Cancerosas , Neoplasias Gástricas , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/epidemiologia , Humanos , Gastrite/imunologia , Gastrite/microbiologia , Gastrite/epidemiologia , Gastrite/patologia , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/imunologia , Helicobacter pylori/patogenicidade , Lesões Pré-Cancerosas/imunologia , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/epidemiologia , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/epidemiologia , Mucosa Gástrica/patologia , Mucosa Gástrica/imunologia , Mucosa Gástrica/microbiologia , Metaplasia , Fatores de Risco , Estômago/patologia , Estômago/imunologia , Estômago/microbiologia , Microbioma Gastrointestinal/imunologia , CamundongosRESUMO
Upregulation of homeoprotein SIX1 in gastric cancer (GC) is related to tumour proliferation and invasion. MicroRNA-7160 (miR-7160) is a homeoprotein SIX1-targeting miRNA that downregulates miR-7160, leading to cancer development. Total gastric cancer samples were collected from six patients, and relative expression levels of SIX1 mRNA and miRNAs were analysed by qRT-PCR. To evaluate the regulation of SIX1 by miR-7160, pGL3-SIX1-mut, pGL3-SIX1, and miR-7160 mimics transfected into cells using lipofectamine 2000. After transfection, proliferation and apoptosis in cultured cells were assessed using the nuclear TUNEL staining and CCK8 reagent, respectively. We demonstrated that the downregulation of miR-7160 in human gastric cancer cells is related to the upregulation of SIX1 mRNA. In gastric cancer cell lines, miR-7160 overexpression could downregulate the expression and inhibit cancer cell proliferation and growth in vitro. However, overexpression of miR-7160 did not increase gastric cancer cell apoptosis. In vitro downregulation of SIX1 decreased vimentin, N-cadherin, and other EMT-related gene expression and increased E-cadherin expression. In brief, miR-7160, by targeting SIX1, inhibits gastric cancer proliferation and cell growth in vitro, which provides an idea for introducing a new treatment option for gastric cancer.
Assuntos
Apoptose , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio , MicroRNAs , Neoplasias Gástricas , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Proliferação de Células/genética , Linhagem Celular Tumoral , Apoptose/genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Metástase Neoplásica , Transição Epitelial-Mesenquimal/genética , Inativação Gênica , Movimento Celular/genéticaRESUMO
BACKGROUND: The roles of the transcriptional factor SIX2 have been identified in several tumors. However, its roles in gastric cancer (GC) progression have not yet been revealed. Our objective is to explore the impact and underlying mechanisms of SIX2 on the stemness of GC cells. METHODS: Lentivirus infection was employed to establish stable expression SIX2 or PFN2 in GC cells. Gain- and loss-of-function experiments were conducted to detect changes of stemness markers, flow cytometry profiles, tumor spheroid formation, and tumor-initiating ability. ChIP, RNA-sequencing, tissue microarray, and bioinformatics analysis were performed to reveal the correlation between SIX2 and PFN2. The mechanisms underlying the SIX2/PFN2 loop-mediated effects were elucidated through tissue microarray analysis, RNA stability assay, IP-MS, Co-Immunoprecipitation, and inhibition of the JNK signaling pathway. RESULTS: The stemness of GC cells was enhanced by SIX2. Mechanistically, SIX2 directly bound to PFN2's promoter and promoted PFN2 activity. PFN2, in turn, promoted the mRNA stability of SIX2 by recruiting RNA binding protein YBX-1, subsequently activating the downstream MAPK/JNK pathway. CONCLUSION: This study unveils the roles of SIX2 in governing GC cell stemness, defining a novel SIX2/PFN2 regulatory loop responsible for this regulation. This suggests the potential of targeting the SIX2/PFN2 loop for GC treatment (Graphical Abstracts).
Assuntos
Retroalimentação Fisiológica , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio , Células-Tronco Neoplásicas , Profilinas , Neoplasias Gástricas , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/metabolismo , Linhagem Celular Tumoral , Profilinas/metabolismo , Profilinas/genética , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Animais , Regiões Promotoras Genéticas/genética , Estabilidade de RNA/genética , Sistema de Sinalização das MAP Quinases , Ligação ProteicaRESUMO
BACKGROUND: Clinical T4 (cT4) stage gastric cancer presents with frequent postoperative recurrence and poor prognosis. This study is to evaluate the oncological efficacy of laparoscopic radical total gastrectomy combined with postoperative prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with cT4N + M0 gastric cancer who received neoadjuvant chemotherapy. METHODS: We reviewed the clinicopathological data of 174 patients with clinical T4 gastric cancer who underwent neoadjuvant chemotherapy followed by laparoscopic radical total gastrectomy between June 2017 and December 2021. Among them, 142 were included in the non-HIPEC group, and 32 in the HIPEC group. Patients in both groups were paired based on propensity score in a 2:1 ratio to assess disparities in tumor recurrence and long-term survival. RESULTS: After matching, there were no significant differences in the clinicopathological data between the two groups. The peritoneum (16.1%) and distant organs (10.9%) were the most frequent locations for recurrence. Prior to matching, the recurrence rates were similar at all sites for both groups. Compared with those in the non-HIPEC cohort, the recurrence rates at all sites, the lung, and the peritoneum were notably lower in the HIPEC cohort. Prior to matching, the 3-year overall survival and disease-free survival rates were similar between the two groups; following matching, the HIPEC group exhibited notably greater survival rates than did the non-HIPEC group. The disparities in survival rates between the groups became even more pronounced after conducting a stratified analysis among patients with stage III disease. CONCLUSIONS: Neoadjuvant chemotherapy combined with prophylactic HIPEC after laparoscopic radical gastrectomy can effectively reduce the rate of peritoneal metastasis in patients with cT4N + M0 advanced gastric cancer and significantly improve the prognosis of such patients, which is of great clinical value.