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BACKGROUND: The treatment of lung adenocarcinoma is difficult due to the limited therapeutic options. Cancer-associated fibroblasts play an important role in the development of cancers. This study aimed to identify a promising molecular target associated with cancer-associated fibroblasts for the treatment of lung adenocarcinoma. METHODS: The Cancer Genome Atlas lung adenocarcinoma dataset was used to screen hub genes associated with cancer-associated fibroblasts via the EPIC algorithm and Weighted Gene Co-expression Network Analysis. Multiple databases were used together with our data to verify the differential expression and survival of COL11A1. Functional enrichment analysis and the single-cell TISCH database were used to elucidate the mechanisms underlying COL11A1 expression. The correlation between COL11A1 and immune checkpoint genes in human cancers was also evaluated. RESULTS: Using the EPIC algorithm and Weighted Gene Co-expression Network Analysis, 13 hub genes associated with cancer-associated fibroblasts in lung adenocarcinoma were screened. Using the GEPIA database, Kaplan-Meier Plotter database, GSE72094, GSE75037, GSE32863, and our immunohistochemistry experiment data, we confirmed that COL11A1 overexpresses in lung adenocarcinoma and that high expression of COL11A1 is associated with a poor prognosis. COL11A1 has a genetic alteration frequency of 22% in patients with lung adenocarcinoma. COL11A1 is involved in the extracellular matrix activities of lung adenocarcinoma. Using the TISCH database, we found that COL11A1 is mainly expressed by cancer-associated fibroblasts in the tumor microenvironment rather than by lung adenocarcinoma cells. Finally, we found that COL11A1 is positively correlated with HAVCR2(TIM3), CD274 (PD-L1), CTLA4, and LAG3 in lung adenocarcinoma. CONCLUSION: COL11A1 may be expressed and secreted by cancer-associated fibroblasts, and a high expression of COL11A1 may result in T cell exhaustion in the tumor microenvironment of lung adenocarcinoma. COL11A1 may serve as an attractive biomarker to provide new insights into cancer therapeutics.

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Tantalum and aluminum on sapphire are widely used platforms for qubits of long coherent time. As quantum chips scale up, the number of Josephson junctions on sapphire increases. Thus, both the uniformity and stability of the junctions are crucial to quantum devices, such as scalable superconducting quantum computer circuit, and quantum-limited amplifiers. By optimizing the fabrication process, especially, the conductive layer during the electron beam lithography process, Al/AlOx/Al junctions of sizes ranging from 0.0169 to 0.04 µm2 on sapphire substrates were prepared. The relative standard deviation of room temperature resistances (RN) - [Formula: see text] of these junctions is better than 1.7% on 15 mm × 15 mm chips, and better than 2.66% on 2 inch wafers, which is the highest uniformity on sapphire substrates has been reported. The junctions are robust and stable in resistances as temperature changes. The resistances increase by the ratio of 9.73% relative to RN as the temperature ramp down to 4 K, and restore their initial values in the reverse process as the temperature ramps back to room temperature. After being stored in a nitrogen cabinet for 100 days, the resistance of the junctions changed by1.16% on average. The demonstration of uniform and stable Josephson junctions in large area paves the way for the fabrication of superconducting chip of hundreds of qubits on sapphire substrates.

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A three-component cascade cyclization catalyzed by copper was employed to synthesize quinoline-4-thiols using easily available diaryliodonium salts, alkynyl sulfides, and nitriles as starting materials. Sulfur atoms play an important role in controlling the regioselectivity, by stabilizing the high-valent vinyl copper intermediate. Meanwhile, the sulfide group at position 4 of quinoline could be further utilized as a transformable group for ipso-transformation and as a directing group for C-H functionalization, affording various multifunctional quinoline derivatives.

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SH3BGRL, an adaptor protein, is upregulated in breast cancers and indicates its tumorigenic role. But the function of SH3BGRL in other types of cancers is largely unknown. Here, we modulate SH3BGRL expression level in two liver cancer cells and conduct both in vitro and in vivo analyses of SH3BGRL in cell proliferation and tumorigenesis. Results demonstrate that SH3BGRL notably inhibits cell proliferation and arrests the cell cycle in both LO2 and HepG2 cells. Molecularly, SH3BGRL upregulates the expression of ATG5 from proteasome degradation as well as the inhibitions of Src activation and its downstream ERK and AKT signaling pathways, which eventually enhance autophagic cell death. The xenograft mouse model reveals that SH3BGRL overexpression can efficiently suppress tumorigenesis in vivo, while the additional silencing ATG5 in SH3BGRL-overexpressing cells attenuates the inhibitory effect of SH3BGRL on both hepatic tumor cell proliferation and tumorigenicity in vivo. The relevance of SH3BGRL downregulation in liver cancers and their progression is validated based on the large-scale tumor data. Taken together, our results clarify the suppressive role of SH3BGRL in tumorigenesis of liver cancer, which would be of help to the diagnosis of liver cancer, while either promoting the autophagy of liver cancer cells or inhibiting the downstream signaling induced from SH3BGRL downregulation would be a promising therapy.

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The authors wish to make the following corrections to this paper [...].

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Background: The synergistic effects of antiangiogenic inhibitor bevacizumab and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) therapy were encouraging in patients with EGFR-mutant advanced NSCLC, though some controversy remains. The specific subgroup of patients who might benefit most from the EGFR-TKI and bevacizumab combination therapy is yet to be determined. Methods: Randomized clinical trials (RCTs) that had compared the clinical efficacy of EGFR-TKI and bevacizumab combination therapy with EGFR-TKI monotherapy in treating EGFR-mutant advanced NSCLC patients published before 23 December 2022 were searched in the Cochrane, PubMed and Embase. We performed a meta-analysis for the overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events with a grade equal or more than 3 (grade≥3 TRAEs). Subgroup analyses of PFS and OS stratified by clinical characteristics and treatment were conducted. Results: We included 10 RCTs involving 1520 patients. Compared with EGFR-TKI monotherapy, addition of bevacizumab to EGFR-TKI resulted in a significantly higher PFS (hazard ratio (HR) = 0.74, 95% confidence interval (95% CI): 0.62-0.87)) and ORR (risk ratio (RR) = 1.07, 95% CI: 1.01-1.13). However, no significant difference in OS (HR = 0.96, 95% CI: 0.83-1.12) was noticed. Patients with EGFR-mutant advanced NSCLC receiving combination therapy showed PFS improvement regardless of gender (male or female), Eastern Cooperative Oncology Group performance status (0 or 1), baseline central nervous system (CNS) metastasis (presence or absence) and EGFR mutation type (19del or 21L858R). Subgroup analyses showed that, with the treatment of bevacizumab and EGFR-TKI, patients who ever smoked achieved significantly better OS and PFS benefits (HR = 0.68, 95% CI: 0.48-0.95; HR = 0.59, 95% CI: 0.46-0.74, respectively), and those aged <75 years and the Asian population had significantly prolonged PFS (HR = 0.69, 95% CI: 0.52-0.91; HR = 0.71, 95% CI: 0.58-0.87; respectively). The superiority of EGFR-TKI and bevacizumab combination therapy against EGFR-TKI monotherapy in improving PFS was more significant in the erlotinib regimen subgroup. The risk of grade≥3 TRAEs was remarkably higher in the combination therapy group (HR = 1.73, 95% CI: 1.39-2.16). Conclusion: Addition of bevacizumab to EGFR-TKI therapy provided significantly better PFS and ORR for EGFR-mutant advanced NSCLC patients, though with higher risk of grade≥3 TRAEs. Patients who ever smoked, aged <75 years, and Asian population might benefit more from the combination regimen. Systematic Review Registration: This systematic review and meta-analysis was registered in the PROSPERO database (CRD42023401926).

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BACKGROUND: The risk factors for cardiovascular and cerebrovascular diseases in young and middle-aged people have not yet been determined. We conducted a meta-analysis to find the risk factors for cardiovascular and cerebrovascular diseases, in order to provide guidance for the prevention of diseases in the young and middle-aged population. METHODS: We searched PubMed, Embase, Cochrane Library from the establishment of the database to Mar 2022. We included case-control or cohort studies reporting risk factors for cardiovascular and cerebrovascular disease in young and middle-aged adults. We excluded repeated publication, research without full text, incomplete information or inability to conduct data extraction and animal experiments, reviews and systematic reviews. STATA 15.1 was used to analyze the data. RESULTS: The pooled results indicated that increased systolic blood pressure was significantly associated with increased risk of any stroke, ischemic stroke and hemorrhagic stroke. Body Mass Index (BMI), current smoking, hypertension, and diabetes were significantly associated with increased risk of any stroke and ischemic stroke. Atrial fibrillation was only significantly associated with increased risk of any stroke. Increased total cholesterol was significantly associated with an increased risk of ischemic stroke, whereas increased triglycerides were significantly associated with a decreased risk of ischemic stroke. In addition, increased hypertension was also significantly associated with an increased risk of acute coronary syndrome. CONCLUSION: Our pooled results show that BMI, current smoking, atrial fibrillation, hypertension, systolic blood pressure, and total cholesterol can be used as risk factors for cardiovascular and cerebrovascular diseases in young people, while triglycerides can be used as protective factors for cardiovascular and cerebrovascular diseases in young and middle-aged adults.

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INTRODUCTION: Major depressive disorder (MDD) represents a worldwide burden on healthcare and the response to antidepressants remains limited. Systems biology approaches have been used to explore the precision therapy. However, no reliable biomarker clinically exists for prognostic prediction at present. The objectives of the Integrated Module of Multidimensional Omics for Peripheral Biomarkers (iMORE) study are to predict the efficacy of antidepressants by integrating multidimensional omics and performing validation in a real-world setting. As secondary aims, a series of potential biomarkers are explored for biological subtypes. METHODS AND ANALYSIS: iMore is an observational cohort study in patients with MDD with a multistage design in China. The study is performed by three mental health centres comprising an observation phase and a validation phase. A total of 200 patients with MDD and 100 healthy controls were enrolled. The protocol-specified antidepressants are selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Clinical visits (baseline, 4 and 8 weeks) include psychiatric rating scales for symptom assessment and biospecimen collection for multiomics analysis. Participants are divided into responders and non-responders based on treatment response (>50% reduction in Montgomery-Asberg Depression Rating Scale). Antidepressants' responses are predicted and biomarkers are explored using supervised learning approach by integration of metabolites, cytokines, gut microbiomes and immunophenotypic cells. The accuracy of the prediction models constructed is verified in an independent validation phase. ETHICS AND DISSEMINATION: The study was approved by the ethics committee of Shanghai Mental Health Center (approval number 2020-87). All participants need to sign a written consent for the study entry. Study findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04518592.

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SLC2A1 plays a pivotal role in cancer glycometabolism. SLC2A1 has been proposed as a putative driver gene in various cancers. However, a pan-cancer analysis of SLC2A1 has not yet been performed. In this study, we explored the expression and prognosis of SLC2A1 in pan-cancer across multiple databases. We conducted genetic alteration, epigenetic, and functional enrichment analyses of SLC2A. We calculated the correlation between SLC2A1 and tumor microenvironment using the TCGA pan-cancer dataset. We observed high expression levels of SLC2A1 with poor prognosis in most cancers. The overall genetic alteration frequency of SLC2A1 was 1.8% in pan-cancer, and the SLC2A1 promoter was hypomethylation in several cancers. Most m6A-methylation-related genes positively correlated with the expression of SLC2A1 in 33 TCGA cancers. Moreover, SLC2A1 was mainly related to the functions including epithelial-mesenchymal transition, glycolysis, hypoxia, cell-cycle regulation, and DNA repair. Finally, SLC2A1 positively associated with neutrophils and cancer-associated fibroblasts in the tumor microenvironment of most cancers and significantly correlated with TMB and MSI in various cancers. Notably, SLC2A1 was remarkably positively correlated with PD-L1 and CTLA4 in most cancers. SLC2A1 might serve as an attractive pan-cancer biomarker for providing new insights into cancer therapeutics.

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Background: Existing scoring systems have limitations in predicting the in-hospital mortality of adult sepsis patients. We aimed to develop and validate a novel risk score for predicting the in-hospital mortality of adult sepsis patients. Methods: The clinical data of 1,335 adult sepsis inpatients were retrospectively analyzed. Enrolled patients were randomly divided into a modeling group and a validation group at a 3:2 ratio. The modeling group (n=801) was used to develop the risk score by univariate and multivariate logistic regression analyses. The score's performance was validated in the validation group (n=534). We classified patients into four risk levels according to the novel risk score. Results: Age, central vein catheterization, mechanical ventilation, vasopressin, Charlson comorbidity index (CCI), respiratory rate (RR), heart rate (HR), Glasgow coma scale (GCS) score, platelet (PLT), hematocrit (HCT), aspartate aminotransferase (AST), and activated partial thrombin time (APTT) were independent risk factors for in-hospital death in adult sepsis patients. Continuous variables were converted into classified variables to develop the risk score, with a total score of 39 points. Adult sepsis patients with low, lower medium, higher medium, and high risk levels had in-hospital mortality rates of 9.8%, 24.7%, 55.8%, and 83.5%, respectively. Conclusions: Compared with the Acute Physiology and Chronic Health Evaluation II scoring system (APACHE II) and the Modified Early Warning Score (MEWS), the novel risk score showed good predictive performance for in-hospital mortality in adult sepsis patients.

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Background: For metachronous second pulmonary adenocarcinoma (msPAD) in patients with resected PAD, the method to distinguish tumour clonality has not yet been well established, which makes it difficult to determine accurate staging and predict prognosis. Methods: Patients received surgery for the primary and encountered msPAD were recruited into the Surveillance, Epidemiology, and End Results database. We extracted overall survival 1 (OS1) for the primary, overall survival 2 (OS2) for the msPAD, and defined interval survival as the interval time between the first and second PAD. Based on the nomogram and recursive partitioning analysis, a tumor, node, metastasis staging system (TNM)-like risk stratification system was established for OS2 on the premise of suspending the dispute of tumor clonality. Results: A total of 1,045 patients were identified. There is no significant association between interval survival and OS2. A TNM-like risk stratification system was established based on the independent pathological factors for prognosis, including tumor diameter (2nd), node metastasis (2nd), grade (2nd), and extrapulmonary metastasis (2nd). The proposed risk stratification system present well capacity in predicting and stratifying prognosis. Compared with the TNM stage system, the proposed risk stratification system presents a smaller Akaike information criterion (AIC) but larger c-index, and generates higher accuracy to predict prognosis at 160 months of follow-up according to the time-dependent receiver operating curve (ROC) curve. Conclusions: In conclusion, the TNM-like risk stratification appears to be suitable for prognostic prediction and risk stratification for msPAD patients with former PAD resection. This model validates and refines the known classification rules based on the easily collected variables, and highlights potentially clinical implications.

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Purpose: DNA methylation heterogeneity is a type of tumor heterogeneity in the tumor microenvironment, but studies on the identification of the molecular heterogeneity of the lung adenocarcinoma genome with respect to DNA methylation sites and their roles in lung cancer progression and prognosis are scarce. Methods: Prognosis-associated DNA methylation subtypes were filtered by the Cox proportional hazards model and then established by unsupervised cluster analysis. Association analysis of these subtypes with clinical features and functional analysis of annotated genes potentially affected by methylation sites were performed. The robustness of the model was further tested by a Bayesian network classifier. Results: Over 7 thousand methylation sites were associated with lung adenocarcinoma prognosis. We identified seven molecular methylation subtypes, including 630 methylation sites. The subtypes yielded the most stable results for differentiating methylation profiles, prognosis, and gene expression patterns. The annotated genes potentially affected by these methylation sites are enriched in biological processes such as morphogenesis and cell adhesion, but their individual impact on the tumor microenvironment and prognosis is multifaceted. Discussion. We revealed that DNA methylation heterogeneity could be clustered and associated with the clinical features and prognosis of lung adenocarcinoma, which could lead to the development of a novel molecular tool for clinical evaluation.

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BACKGROUND: Despite 3-year survival being used as a primary endpoint in some randomized controlled trials (RCTs), limited evidence supports the use of intermediate endpoints to evaluate the effect of new therapies in esophageal squamous cell cancer (ESCC). This study aimed to systematically evaluate progression-free survival at 3 years (3-year PFS) and overall survival (OS) among patients with ESCC. METHODS: We identified 528 patients newly diagnosed with locally advanced ESCC who received definitive radiotherapy. OS was compared with an age- and sex-matched general Chinese population using the standardized mortality ratio (SMR). Regression analysis was used to validate the correlation between PFS and OS using published data. RESULTS: The annual risk of progression decreased to 11.5% after 3 years. Patients who did not achieve 3-year PFS had a median postprogression survival (PPS) of 7.3 months, with a 5-year OS rate of 9.6% and a SMR of 15.0 (95% confidence interval [CI], 12.9-17.5). Conversely, the SMR for patients who achieved 3-year PFS was 0.9 (95% CI, 0.6-1.3). We observed a significant correlation between log hazard ratio (HR) (PFS) and log HR (OS) at the trial level (r = 0.89; 95% CI, 0.88-0.90). The strongest correlation was observed between 3-year PFS and 5-year OS in RCTs and retrospective studies. CONCLUSIONS: Patients exhibiting progression within 3 years experienced poor survival, whereas patients achieving 3-year PFS had excellent outcomes. Our study supports 3-year PFS as a reliable primary endpoint for study design and risk stratification in locally advanced ESCC.

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Background: The prognostic value of ground glass opacity (GGO) in stage IA non-small cell lung cancer (NSCLC) has been widely recognized. However, studies investigating its value in the related stage IB-IIA lung adenocarcinoma (LUAD) remains lacking. The impact of adjuvant chemotherapy (ACT) on pathological stage IB-IIA LUAD is also controversial. Materials and Methods: We retrospectively reviewed the clinical records of 501 patients with pathological stage IB-IIA LUAD at the Sun Yat-sen University Cancer Center from January 2008 to June 2018. We calculated and compared survival curves using the Kaplan-Meier test and log-rank test. Cox regression models were performed to determine independent prognostic factors of disease-free survival (DFS) and overall survival (OS). We established nomograms to predict the OS and DFS of LUAD patients. Calibration and receiver operator characteristic curves were conducted to assess the predictive performance of two nomograms. Based on the nomogram, we identified candidate patients that may most benefit from ACT after surgery. Results: The number of patients with pure solid, part GGO, and pure GGO nodules was 240, 242, and 19, respectively, and 125 patients who received ACT. Patients with consolidation-to-tumor ratio (CTR) <0.75 had longer OS (P = 0.026) and DFS (P = 0.003). Pathological tumor size and at least 10 lymph nodes (LNs) resection were independent prognostic factors of both OS and DFS. CTR <0.75 was positively associated with DFS. The C-index of nomograms predicting individual OS and DFS was 0.660 and 0.634, respectively. Based on the nomogram for OS, ACT was found to be a positive prognostic indicator of OS (P = 0.031, HR = 0.5141, 95% CI 0.281-0.942) in patients with nomogram total points ≥5. Conclusion: CTR <0.75 is associated with a better DFS in patients with stage IB-IIA LUAD. Nomograms developed by integrating pathological tumor size, at least 10 LNs resection, and CTR ≥0.75 for predicting individual OS and DFS displayed a good predictive capacity and clinical value, which were also proved to be a useful tool for selecting patients most benefiting from ACT.

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BACKGROUND: For metachronous second pulmonary squamous cell carcinoma (msPSC) in patients with resected PSC, the method to distinguish tumour clonality has not yet been well established, which makes it difficult to determine accurate staging and predict prognosis. METHODS: Patients who underwent surgery for first PSC and encountered msPSC were recruited from the Surveillance, Epidemiology, and End Results (SEER) database. We extracted overall survival 1 (OS1) for the first PSC, overall survival 2 (OS2) for msPSC, and interval survival for the time interval between the first and second PSC. The nomogram was calibrated for OS2, and recursive partitioning analysis (RPA) was performed for risk stratification. RESULTS: A total of 617 patients were identified. Several independent prognostic factors were identified and integrated into the nomogram for OS2, including gender, age (2nd), nodal status (1st), node metastasis (2nd), and extrapulmonary metastasis (2nd). The calibration curves showed optimal agreement between the predictions and actual observations, and the c-index was 0.678. Surgery was associated with longer survival for msPSC patients. The prognosis of sublobectomy was comparable and inferior to that of lobectomy in the low- and moderate-risk groups, respectively. Radiotherapy was associated with better outcomes in patients who did not undergo surgery. CONCLUSIONS: The RPA-based clinical nomogram appears to be suitable for the prognostic prediction and risk stratification of OS2 in msPSC. This practical system may help clinicians make decisions and design clinical studies.

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Circular RNA is related to the tumorigenesis of various cancers. Circular RNA hsa_circ_0020123 (circ_0020123) has been uncovered to promote non-small cell lung cancer (NSCLC) progression. However, the regulatory mechanism of circ_0020123 in NSCLC is unclear. The quantitative real-time polymerase chain reaction was employed to detect the levels of circ_0020123, microRNA (miR)-193a-3p, and IRF4 interferon regulatory factor 4 (IRF4) in NSCLC tissues and cells. Loss-of-function experiments were performed to analyze the impacts of circ_0020123 silencing on NSCLC cell malignancy, autophagy, and glycolysis. Protein levels were detected using western blotting. The regulatory mechanism of circ_0020123 was analyzed by bioinformatics analysis and validated by the dual-luciferase reporter, RNA immunoprecipitation assay, and RNA pull-down assay. Xenograft assay was performed to verify the biological function of circ_0020123. We observed an overt elevation in circ_0020123 expression in NSCLC samples and cells, and NSCLC patients with high circ_0020123 expression had a poor prognosis. Circ_0020123 knockdown constrained xenograft tumor growth in vivo and curbed cell proliferation, migration, and glycolysis, and accelerated cell apoptosis and autophagy in NSCLC cells in vitro. Circ_0020123 could absorb miR-193a-3p to regulate IRF4 expression. miR-193a-3p silencing overturned circ_0020123 knockdown-mediated impacts on NSCLC cell malignancy, autophagy, and glycolysis. And IRF4 overexpression reversed miR-193a-3p mimic-mediated effects on NSCLC cell malignancy, autophagy, and glycolysis. Circ_0020123 promoted glycolysis and tumor growth by upregulating IRF4 through sequestering miR-193a-3p in NSCLC, offering a novel mechanism by which circ_0020123 is responsible for the malignancy, autophagy, and glycolysis of NSCLC cells.

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This study quantitatively evaluated the effect of chloride (Cl-) on the radical distribution and micropollutant degradation in the UV/peroxydisulfate AOP using both experimental and modeling approaches. Results showed that SO4•- was significantly scavenged by Cl- at environmentally relevant concentrations (1-5000 mg/L). With increasing Cl- concentrations from 1 to 5000 mg/L, Cl- transformed SO4•- to HO• and then to Cl2•-. The critical role of Cl2•- as a precursor of HO• in the radical transformation was highlighted. The inhibitory effects of bicarbonate and dissolved organic matter (DOM) on micropollutant degradation was more significant in the presence of Cl- than that in the absence of Cl-, mainly due to the consumption of Cl2•- by bicarbonate and DOM. Using the model-predicted radical concentrations in the UV/peroxydisulfate process in the presence of different concentrations of Cl-, the degradation rate constants of 34 micropollutants and the contributions of each radical to the degradation were predicted and compared. The findings improved the fundamental understanding of the Cl- effect on radical transformation and micropollutant degradation in the SO4•--based AOPs. The model enables to foresee whether a SO4•--based AOP is effective for the degradation of a certain micropollutant in the water with known concentrations of Cl-.

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Autophagy-related long-chain noncoding ribonucleic acids play a vital role in the development of esophageal adenocarcinoma. This study aimed to construct a prognostic model of autophagy-related long-chain noncoding ribonucleic acids and identify potential therapeutical targets for esophageal adenocarcinoma. We downloaded 261 long-chain noncoding RNA transcript samples and clinical data of 87 esophageal adenocarcinoma patients from the Cancer Genome Atlas and 307 autophagy-related genes from www.autophagy.com. We performed Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses and Gene Set Enrichment Analysis to determine risk characteristics and bioinformatics functions of signal transduction pathways. Univariate and multivariate Cox regression analyses were used to determine the correlation between autophagy-related long-chain noncoding ribonucleic acids and independent risk factors. The receiver operating characteristic analysis was used to evaluate the feasibility of the prognostic model. Finally, we performed survival analysis, risk analysis and independent prognostic analysis to verify the prognostic model of esophageal adenocarcinoma. We identified 22 autophagic long-chain noncoding ribonucleic acids that were highly correlated with the overall survival of esophageal adenocarcinoma patients. The areas under the receiver operating characteristic curve (0.941) and the calibration curve were significantly similar. Moreover, univariate and multivariate Cox regression analyses indicated that autophagy-related long-chain noncoding ribonucleic acids were independent predictors of esophageal adenocarcinoma. We found that autophagy-related long-chain noncoding ribonucleic acids might affect tumor development and prognosis in esophageal adenocarcinoma patients. The findings indicate that the prognostic model of esophageal adenocarcinoma has potential therapeutic applications in patients with esophageal adenocarcinoma.

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Lay summary: Patients with a family history of cancer, especially digestive tract cancer and esophageal cancer, a family history of cancer in the first degree, and more than one relative affected by cancer were associated with favorable survival when compared to those without a family history of cancer. Precis for use in the Table of Contents: A family history of cancer is a favorable independent prognostic factor in ESCC. Patients with a family history of cancer, especially digestive tract cancer and esophageal cancer, a family history of cancer in the first degree, and more than one relative affected by cancer were associated with favorable survival when compared to those without a family history of cancer. Background: A family history of cancer (FH) is closely associated with the risk and survival of many cancers. However, the effect of FH on the prognosis of patients with esophageal squamous cell carcinoma (ESCC) remains unclear. We performed a large cohort study in the Chinese population to obtain insight into the prognostic value of FH in patients with operable ESCC. Methods: A total of 1,322 consecutive patients with thoracic ESCC who had undergone esophagectomy between January 1997 and December 2013 were included. The FH group included patients with any degree of FH, while the non-FH group included patients without any degree of FH. In total, 215 patients with FH and 215 without FH were matched using the propensity score matching analysis method to adjust for differences in baseline variables between the two groups. The impact of FH on disease-free survival (DFS) and overall survival (OS) was estimated using the Kaplan-Meier method and Cox's proportional hazards models. Results: Before matching, 280 (21.2%) patients were included in the FH group and 1,042 (78.8%) in the non-FH group. FH was associated with early pathological T stage (p = 0.001), lymph node-negative status (p = 0.022), and early pathological stage (p = 0.006). After matching, FH was an independent prognostic factor for DFS and OS in ESCC patients. Patients with FH had 35% lower risk of disease progression (hazard ratio [HR] = 0.65, 95% CI: 0.51-0.84, p = 0.001) and 34% lower risk of death (HR = 0.66, 95% CI: 0.51-0.86, p = 0.002) than those without FH. Patients with a family history of digestive tract cancer (FH-DC), a family history of esophageal cancer (FH-EC), FH in first-degree relatives (FH-FD), and more than one relative affected by cancer were associated with favorable DFS and OS as compared to those without FH. Conclusion: FH is a favorable independent prognostic factor in ESCC. Patients with FH, especially those with FH-DC, FH-EC, FH-FD, and more than one relative affected by cancer, had improved survival.