crossing96/oncoscreening huggingface dataset:
Multiregion sequencing and subclonal analysis reveal intratumoral heterogeneity in esophageal squamous cell carcinoma.	PURPOSE: The aim of this study was to investigate intratumoral genomic heterogeneity and subclonal structure of esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Multiregion whole-exome sequencing was performed on 24 surgically acquired tumor samples from five untreated ESCC patients collected in 2019 to determine the heterogeneity of mutational landscape within tumors. Phylogenetic analysis and mutation process analysis were used to explore the distribution and dynamic changes of mutation spectrum, and subclone analysis was used to explore the subclonal composition and spatial structure of ESCC. RESULTS: An average of 60.2% of mutations were found heterogenous. TP53 and NOTCH1 mutations were confirmed to be early events, and mutations unique in different tumor regions showed a pattern of branching evolution. A large proportion of mutations were associated with abnormal activity of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) family, and significant differences in mutation types between trunk and branch variants were found. Subclonal structure exhibited spatial correspondence and spatial limitations, and different genomic features were characterized between close and distant clones. CONCLUSIONS: There is significant intratumoral genomic heterogeneity in the five ESCCs, and their subclonal structure is related to spatial locations.	esophagus
RATIONALE 311: tislelizumab plus concurrent chemoradiotherapy for localized esophageal squamous cell carcinoma.	Definitive chemoradiotherapy is the standard of care for inoperable locoregionally advanced esophageal squamous cell carcinoma (ESCC). Immune checkpoint inhibitors such as anti-PD-1/PD-L1 antibodies have led to a paradigm shift in advanced, metastatic ESCC treatment; however, the effect of incorporating checkpoint inhibitors in the definitive management of ESCC is unclear. Tislelizumab is an anti-PD-1 antibody specifically engineered to minimize FcɣR binding on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. The RATIONALE 311 study described here (BGB-A317-311; NCT03957590) is a registrational multicenter, double-blind, placebo-controlled, randomized, Phase III clinical trial designed to evaluate the efficacy and safety of tislelizumab combined with concurrent chemoradiotherapy in patients with inoperable localized ESCC.	esophagus
HOTTIP is upregulated in esophageal cancer and triggers the drug resistance.	PURPOSE: To explore the role of HOTTIP in the development of esophageal cancer and the drug resistance. METHODS: Serum level of HOTTIP in esophageal cancer patients was detected by RT-PCR. After treatment with different concentrations of Adriamycin (ADM) in Eca109 cells for 24 h, IC50 was measured by MTT assay. Subsequently, Eca109 cells were treated with 0, 0.2, 0.4 or 0.8 μg/ml ADM, respectively, followed by extraction of extracellular vesicles (EVs). HOTTIP level in EVs was detected. In addition, Eca109 cells were pre-treated with EVs for 48 h, and different concentrations of ADM for another 24 h. IC50, cell cycle determination and relative levels of HOTTIP and ABCG2 were examined. Pearson correlation test was conducted to assess the correlation between levels of HOTTIP and ABCG2. RESULTS: Serum level of HOTTIP was higher in esophageal cancer patients. IC50 in ADM-treated Eca109 cells for 24 h was 0.43±0.02 μg/ml. EVs1-4 were respectively isolated from Eca109 cells treated with 0, 0.2, 0.4 or 0.8 μg/ml ADM for 24 h, respectively. HOTTIP remained the highest level in EVs4 than the other three groups. Notably, IC50 was much higher in Eca109 cells incubated with EVs4 than those treated with EVs1-3. EVs4 intervention in Eca109 cells for 48 h markedly increased the proliferation index (PI), and relative levels of HOTTIP and ABCG2 than the other three groups. HOTTIP displayed a positive correlation with ABCG2 in Eca109 cells. CONCLUSIONS: HOTTIP is highly expressed in serum of esophageal cancer patients. EVs-containing HOTTIP regulates drug resistance in esophageal cancer by positively activating ABCG2.	esophagus
Prediction of overall survival in patients with Stage I esophageal cancer: A novel web-based calculator.	BACKGROUND AND AIMS: In this study, we aimed to develop a convenient web-based calculator to predict the overall survival (OS) of patients with Stage I esophageal cancer (EC). METHODS: Data of 1664 patients, between 2004 and 2015, were extracted from the Surveillance, Epidemiology, and End Results database. Least absolute shrinkage and selection operator regression was employed to sift variables; subsequently, Cox proportional hazards regression model was built. We applied the enhanced bootstrap validation to appraise the discrimination and calibration of the model. Clinical benefit was measured using decision curve analysis (DCA). Thereafter, a web-based calculator based on the model, which could be used to predict the 1-, 3-, and 5-year OS rates, was developed. RESULTS: Race, age, histologic type, grade, N stage, and therapeutic methods were selected. C-indices of the prediction model in the training and validation groups were 0.726 (95% confidence interval [CI], 0.679-0.773) and 0.724 (95% CI, 0.679-0.769), respectively. Calibration curves showed good agreement between the groups. The DCA demonstrated that the prediction model is clinically useful. CONCLUSIONS: The prediction model we developed showed a good performance in calculating the OS rates in patients with Stage I EC. The web-based calculator is available at https://championship.shinyapps.io/dynnomapp/.	esophagus
Surgical intervention for late gastric conduit obstruction.	OBJECTIVES: Gastric emptying delay after oesophagectomy may occur in conduits exposed to pleural forces of respiration or anatomic obstruction. Remedial operations addressing both causes are rarely reported. The study aim was to categorize severe gastric conduit obstruction (GCO) and report the outcome of surgical revision. METHODS: A single-institution, retrospective study of gastric conduit revision following oesophagectomy for oesophageal cancer investigated incidence, risk factors and categories of conduit obstruction. Evaluation consisted of contrast studies, computed tomogram and endoscopy. Interventions were categorized according to obstructive cause and included pyloroplasty, hiatal hernia reduction and thoraco-abdominal conduit repositioning. RESULTS: Among 1246 oesophagectomies over a 17-year period, 14 patients (1.1%) required post-oesophagectomy relief of GCO. Two additional patients presented after oesophagectomy elsewhere. Before oesophagectomy, 18.8% (3/16) and 62.5% (10/16) of patients were on chronic opioid and psychotropic medications, respectively. Distinct anatomic features separated obstruction into 3 categories: pyloric in 31% (5/16), extrinsic in 12.5% (2/16) and combined in 56.3% (9/16). Operative revision led to complete symptom resolution in 50% (8/16) of patients and symptom improvement in 43.8% (7/16) of patients. One patient (1/16, 6.25%) in the combined obstruction group did not improve with surgical revision. CONCLUSIONS: GCO after oesophagectomy rarely requires surgical revision. Potential association with medications affecting oesophageal and gastric motility requires further investigation. Classification of obstruction identifies a patient subset with lower success after surgical revision.	esophagus
UBE2T Contributes to the Prognosis of Esophageal Squamous Cell Carcinoma.	Background: The ubiquitin-conjugating enzyme E2 T (UBE2T) has been shown to contribute to several types of cancer. However, no publication has reported its implication in esophageal squamous cell cancer (ESCC). Methods: We explored several public databases, including The Cancer Genome Atlas (TCGA), Oncomine, and gene expression Omnibus (GEO). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and gene set enrichment analysis (GSEA) were adopted to explore involved signaling pathways. We used R software to develop prognostic gene signatures with the LASSO and stepwise Cox regression analysis, separately. Immunohistochemistry staining was performed to detect UBE2T in 90 ESCC patients, followed by survival analysis. We also used an R package pRRophetic to evaluate chemotherapy sensitivity for the TCGA-ESCC cohort. Results: We found significantly increased UBE2T transcript levels and DNA copy numbers in ESCC tissues. UBE2T was associated with the p53 signaling pathway, cell cycle, Fanconi anemia pathway, and DNA replication, as indicated by Go, KEGG pathway enrichment analysis. These pathways were also upregulated in ESCC. The prognostic signatures with UBE2T-associated genes could stratify ESCC patients into low- and high-risk groups with significantly different overall survival in the TCGA-ESCC cohort. We also validated the association of UBE2T with unfavorable survival in 90 ESCC patients recruited for this study. Moreover, we found that the low-risk group was significantly more sensitive to chemotherapy than the high-risk group. Conclusions: UBE2T is involved in the development of ESCC, and gene signatures derived from UBE2T-associated genes are predictive of prognosis in ESCC.	esophagus
Identification of Prognostic Related Genes of Tumor Microenvironment Derived From Esophageal Cancer Patients.	Background and Objective: Esophageal cancer (ESCA) is a commonly occurring cancer worldwide with poor survival and limited therapeutic options. Due to the lack of biomarkers that facilitate early detection, its treatment remains a great challenge. This study aims at identifying the tumor microenvironment (TME)-related genes, which might affect prognosis and accelerate clinical treatment for ESCA patients. Methods: We integrated the expression profiles from ESCA patients in The Cancer Genome Atlas. Then, we determined the stromal and immune scores of each sample using the R package. The Gene Expression Omnibus database was used to validate the expression profile of the key genes. Results: Tumor mutational burden showed a significant difference between the groups of ESCA patients with high and low ESTIMATE scores. We identified 859 intersection genes among patients with different immune and stromal scores. Moreover, gene ontology analysis demonstrated that these 859 intersection genes were closely related to adaptive immune response and regulation of lymphocyte activation. Kyoto Encyclopedia of Genes and Genomes showed the enrichment of cytokine-cytokine receptor interaction and chemokine signaling pathway in the TME. Furthermore, the protein-protein interaction network consisted of 175 nodes. We selected 35 hub genes, including ITGAM, CXCL10, CCR2, CCR5, and CCR1. Of these, 23 intersection genes predicted the overall survival rate. C1QA and FCER1G correlated with overall survival of the ESCA patients in the two databases. Conclusion: We identified a set of stromal and immune score-related prognostic differentially expressed genes that could influence the complexity of the TME. C1QA and FCER1G were identified and validated with respect to their role in the progression of ESCA.	esophagus
Esophagectomy or Total Gastrectomy for Siewert 2 Gastroesophageal Junction (GEJ) Adenocarcinoma? A Registry-Based Analysis.	BACKGROUNDS: Due to a lack of randomized and large studies, the optimal surgical approach for Siewert 2 gastroesophageal junctional (GEJ) adenocarcinoma remains unknown. This population-based cohort study aimed to compare survival between esophagectomy and total gastrectomy for the treatment of Siewert 2 GEJ adenocarcinoma. METHODS: Data from the National Cancer Database (NCDB) from 2010 to 2016 was used to identify patients with non-metastatic Siewert 2 GEJ adenocarcinoma who received either esophagectomy (n = 999) or total gastrectomy (n = 8595). Propensity score-matching (PSM) and multivariable analyses were used to account for treatment selection bias. RESULTS: Comparison of the unmatched cohort's baseline demographics showed that the patients who received esophagectomy were younger, had a lower burden of medical comorbidities, and had fewer clinical positive lymph nodes. The patients in the unmatched cohort who received gastrectomy had a significantly shorter overall survival than those who received esophagectomy (median, 47 vs. 68 months [p < 0.001]; 5-year survival, 45 % vs. 53 %). After matching, gastrectomy was associated with significantly reduced survival compared with esophagectomy (median, 51 vs. 68 months [p < 0.001]; 5-year survival, 47 % vs. 53 %), which remained in the adjusted analyses (hazard ratio [HR], 1.22; 95 % confidence interval [CI], 1.09-1.35; p < 0.001). CONCLUSIONS: In this large-scale population study with propensity-matching to adjust for confounders, esophagectomy was prognostically superior to gastrectomy for the treatment of Siewert 2 GEJ adenocarcinoma despite comparable lymph node harvest, length of stay, and 90-day mortality. Adequately powered randomized controlled trials with robust surgical quality assurance are the next step in evaluating the prognostic outcomes of these surgical strategies for GEJ cancer.	esophagus
Clinicopathological and prognostic values of PD-L1 expression in oesophageal squamous cell carcinoma: a meta-analysis of 31 studies with 5368 patients.	Several immune checkpoint inhibitors targeting programmed death ligand 1 (PD-L1)/programmed death 1 have successfully improved the prognosis of oesophageal squamous cell carcinoma (ESCC) with approval in certain countries. However, whether the expression of PD-L1 is associated with the degree of benefit is unclear yet and a unified standard of antibody and cut-off value of PD-L1 detection is also lacking. The current meta-analysis then aimed to explore the association between PD-L1 expression and clinicopathological features as well as prognosis in ESCC.A systematic search on PubMed, Embase, Cochrane Library and Web of Science databases was performed up to 30 March 2021. The correlation between PD-L1 expression and clinicopathological features, as well as prognosis in ESCC, was estimated with the random-effects model.A total of 5368 patients from 31 retrospective studies were enrolled. The overexpression of PD-L1 was significantly associated with lymph node metastasis (OR 1.342, 95% CI 0.995 to 1.809, p=0.050) and distant metastasis (OR 1.516, 95% CI 1.001 to 2.294, p=0.050). The pooled HR showed that PD-L1 overexpression was significantly correlated with poor overall survival (OS) of patients with ESCC (HR 1.306, 95% CI 1.108 to 1.539, p<0.010) but not disease-free survival (DFS) (HR 1.180, 95% CI 0.937 to 1.487, p=0.160). Heterogeneity decreased significantly in subgroup analyses. The overexpression of PD-L1 was associated with poor DFS at the cut-off point of ≥1% (HR 1.642, 95% CI 1.367 to 1.973, p<0.010; I(2)=0%) and worse OS at the cut-off point of ≥10% (HR 1.575, 95% CI 1.175 to 2.111, p<0.010; I(2)=0%).The overexpression of PD-L1 was correlated with lymph node and distant metastasis as well as poor survival of ESCC.	esophagus
Clinically actionable findings on surveillance EGD in asymptomatic patients with Lynch syndrome.	BACKGROUND AND AIMS: Lynch syndrome (LS) predisposes patients to multiple cancers including of the gastric and small bowel. Data supporting EGD surveillance in LS are limited. Our aim is to describe upper GI (UGI) findings in asymptomatic LS patients undergoing EGD surveillance within a hereditary colorectal cancer registry. METHODS: Asymptomatic patients with LS who underwent ≥1 surveillance EGD were included. Demographics, genotype, and EGD findings were reviewed. The frequency of clinically actionable findings including neoplasia (cancer, adenomas), Barrett's esophagus (BE), Helicobacter pylori, and hyperplastic polyps >5 mm were assessed. RESULTS: Three hundred twenty-three patients underwent 717 EGDs starting at a median age of 49.5 years. On average, each patient had 2 EGDs with an interval of 2.3 years between examinations. Clinically actionable findings were identified in 57 patients (17.6%). On baseline EGD 27.7% of findings were identified, with the remainder on surveillance EGD over an average of 3.5 years. Five asymptomatic patients (1.5%) had an UGI cancer detected during surveillance, all at early stage, including 1 patient each with BE-related esophageal adenocarcinoma, gastric neuroendocrine tumor, and gastric adenocarcinoma and 2 patients with duodenal adenocarcinoma. Two cancers were found on baseline EGD and 3 on follow-up EGD. CONCLUSIONS: Clinically actionable findings were found in approximately 1 in 6 asymptomatic patients with LS undergoing EGD surveillance. Five patients (1.5%) were diagnosed with cancer, all detected at an early stage. These data suggest that both baseline and follow-up EGD surveillance are effective in detecting early-stage UGI cancers in asymptomatic patients with LS.	esophagus
Development and validation of a survival model for esophageal adenocarcinoma based on autophagy-associated genes.	Autophagy is a highly conserved catabolic process which has been implicated in esophageal adenocarcinoma (EAC). We sought to investigate the biological functions and prognostic value of autophagy-related genes (ARGs) in EAC. A total of 21 differentially expressed ARGs were identified between EAC and normal samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were then applied for the differentially expressed ARGs in EAC, and the protein-protein interaction (PPI) network was established. Cox survival analysis and Lasso regression analysis were performed to establish a prognostic prediction model based on nine overall survival (OS)-related ARGs (CAPN1, GOPC, TBK1, SIRT1, ARSA, BNIP1, ERBB2, NRG2, PINK1). The 9-gene prognostic signature significantly stratified patient outcomes in The Cancer Genome of Atlas (TCGA)-EAC cohort and was considered as an independently prognostic predictor for EAC patients. Moreover, Gene set enrichment analysis (GSEA) analyses revealed several important cellular processes and signaling pathways correlated with the high-risk group in EAC. This prognostic prediction model was confirmed in an independent validation cohort (GSE13898) from The Gene Expression Omnibus (GEO) database. We also developed a nomogram with a concordance index of 0.78 to predict the survival possibility of EAC patients by integrating the risk signature and clinicopathological features. The calibration curves substantiated favorable concordance between actual observation and nomogram prediction. Last but not least, Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2), a member of the prognostic gene signature, was identified as a potential therapeutic target for EAC patients. To sum up, we established and verified a novel prognostic prediction model based on ARGs which could optimize the individualized survival prediction in EAC.	esophagus
Artificial Intelligence in Surveillance of Barrett's Esophagus.	A study by Waterhouse and colleagues in a previous issue of Cancer Research describes the development and prospective validation of an artificial intelligence approach in conjunction with spectral imaging to enhance endoscopic detection of Barrett's esophagus-related neoplasia. The authors developed a novel spectral endoscope with external optics suitable for routine Barrett's esophagus surveillance with diffuse tissue reflectance to define multispectral data correlated with histopathology. A convolutional neural network was trained on the absis of the spectral signatures acquired as part of a small, prospective clinical trial to distinguish Barrett's esophagus from Barrett's esophagus neoplasia. The results from the study suggest the utility of artificial intelligence for diagnosis of Barrett's esophagus.See related article by Waterhouse et al., Cancer Res 2021;81:3415-25.	esophagus
Prognostic value of patient-reported quality of life for survival in oesophagogastric cancer: analysis from the population-based POCOP study.	BACKGROUND: Accumulating evidence of trials demonstrates that patient-reported health-related quality of life (HRQoL) at diagnosis is prognostic for overall survival (OS) in oesophagogastric cancer. However, real-world data are lacking. Moreover, differences in disease stages and tumour-specific symptoms are usually not taken into consideration. The aim of this population-based study was to assess the prognostic value of HRQoL, including tumour-specific scales, on OS in patients with potentially curable and advanced oesophagogastric cancer. METHODS: Data were derived from the Netherlands Cancer Registry and the patient reported outcome registry (POCOP). Patients included in POCOP between 2016 and 2018 were stratified for potentially curable (cT1-4aNallM0) or advanced (cT4b or cM1) disease. HRQoL was measured with the EORTC QLQ-C30 and the tumour-specific OG25 module. Cox proportional hazards models assessed the impact of HRQoL, sociodemographic and clinical factors (including treatment) on OS. RESULTS: In total, 924 patients were included. Median OS was 38.9 months in potentially curable patients (n = 795) and 10.6 months in patients with advanced disease (n = 129). Global Health Status was independently associated with OS in potentially curable patients (HR 0.89, 99%CI 0.82-0.97), together with several other HRQoL items: appetite loss, dysphagia, eating restrictions, odynophagia, and body image. In advanced disease, the Summary Score was the strongest independent prognostic factor (HR 0.75, 99%CI 0.59-0.94), followed by fatigue, pain, insomnia and role functioning. CONCLUSION: In a real-world setting, HRQoL was prognostic for OS in patients with potentially curable and advanced oesophagogastric cancer. Several HRQoL domains, including the Summary Score and several OG25 items, could be used to develop or update prognostic models.	esophagus
The prognostic performance of the log odds of positive lymph nodes in patients with esophageal squamous cell carcinoma: A population study of the US SEER database and a Chinese single-institution cohort.	BACKGROUND: The purpose of this study was to assess the prognostic performance of the log odds of positive lymph nodes (LODDS) value compared with the pathological N stage and lymph node ratio (LNR) in patients with esophageal squamous cell carcinoma (ESCC). METHOD: In total 1144 patients diagnosed with ESCC from the Surveillance, Epidemiology, and End Results (SEER) database and 930 patients from our validation cohort were eligible. Kaplan-Meier plotter and multivariate Cox proportional hazards models were conducted to investigate the prognostic value of the N stage, LNR stage, and LODDS stage. The homogeneity, discriminatory ability, and monotonicity of these variables were evaluated using the linear trend χ(2) test, likelihood ratio χ(2) test, Akaike information criterion (AIC), and consistency index (C-index) to determine the potential superiorities. RESULTS: The prognostic LODDS cutoff values were determined to be -1.49 and -0.55 (p < 0.001). Univariate analyses showed significant association among the N, LNR, and LODDS stages and overall survival of the patients (all p < 0.001). Multivariate analyses confirmed that the LODDS stage remained an independent prognostic indicator in both the SEER database and our validation cohort. Subgroup analyses identified the ability of LODDS stage to distinguish heterogeneous patients within various groups in both independent databases. Furthermore, the model with the highest C-index and smallest AIC value was the one incorporating the LODDS stage among the three investigated nodal classifications of both cohorts. CONCLUSION: The novel LODDS stage demonstrated better prognostic performance than the traditional N or LNR stages in ESCC patients. It can serve as an auxiliary factor to improve prognostic performance and can be applied to evaluate the lymph node status to increase the precision of staging and evaluation of survival.	esophagus