crossing96/oncoscreening huggingface dataset:
Potentially functional genetic variants of the notch signaling pathway genes predict survival of Chinese patients with esophageal squamous cell carcinoma.	BACKGROUND: The Notch signaling pathway is involved in the progression of esophageal squamous cell carcinoma (ESCC), although the roles of single nucleotide polymorphisms (SNPs) of the Notch signaling pathway genes in the process remain unknown. METHODS: The present study included 1009 patients with histopathologically diagnosed ESCC at Fudan University Shanghai Cancer Center. Two-stage multivariate Cox proportional hazards regression analysis was used to estimate associations between 13,248 SNPs in 103 Notch signaling pathway genes and overall survival of the patients. RESULTS: We found that overall survival of the patients was significantly associated with genotypes of HDAC9 rs1729318 (AT+TT vs. AA: hazard ratio = 1.44, 95% confidence interval = 1.16-1.80, p(combined)  = 0.001) and HDAC9 rs1339555498 (GT + TT vs. GG: hazard ratio = 1.38, 95% confidence interval = 1.10-1.74, p(combined) = 0.005). Further receiver operator characteristic (ROC) curve analysis indicated that the model with both available clinical factors and these two SNPs improved the area under the ROC curve compared to the model with clinical factors only (1-year: 0.66 vs. 0.64, p = 0.034). Additional expression quantitative trait loci analysis showed that the rs1729318 T variant genotypes were associated with increased mRNA expression levels of HDAC9 in normal esophageal muscular tissue (p = 0.003). CONCLUSIONS: The results suggest that these two potential functional SNPs on HDAC9 may serve as biomarkers for predicting survival of ESCC patients. However, further studies are needed to confirm these findings.	esophagus
Deleterious alterations of DNA damage response and repair genes and clinical benefit to anti-PD-1 therapy in esophageal squamous cell carcinoma.	BACKGROUND: Although DNA damage response and repair (DDR) gene alteration has been demonstrated as a biomarker for anti-PD-1 therapy in several cancer types, its role in esophageal squamous cell carcinoma (ESCC) is unknown. METHODS: Patients with advanced ESCC treated with anti-PD-1-based immunotherapy were enrolled. Tumor response was evaluated according to RECIST 1.1. Archival ESCC tissues were analyzed using FoundationOne CDx. Deleterious alterations, defined by loss of function, of DDR genes were correlated with patient survival by Cox proportional hazards model. The prognostic significance of deleterious alterations of DDR genes in The Cancer Genome Atlas (TCGA)-ESCC cohort was explored. RESULTS: Forty-three patients were enrolled. The objective response rate (ORR) was 19%. The median tumor mutational burden was 4 mutations/Mb (0-20); none of the tumors were microsatellite instable. Compared with patients with wild-type or other alterations of DDR genes (N = 35, 81%), those with deleterious alterations of DDR genes (N = 8, 19%) had a higher ORR (38 vs. 14%), longer median progression-free survival (4.1 vs. 2.0 months), and significantly longer median overall survival (OS; 27.7 vs. 6.1 months, P = 0.011). In multivariate analysis, harboring deleterious alterations of DDR genes was a favorable prognostic factor for OS (HR = 0.31 [95% CI: 0.11-0.91], P = 0.033). In the TCGA-ESCC cohort, the presence of deleterious alterations of DDR genes was not a favorable prognostic factor. CONCLUSIONS: Deleterious alterations of DDR genes may be associated with improved prognosis and efficacy of anti-PD-1 therapy in patients with advanced ESCC.	esophagus
Alpha Protein Kinase 2 Promotes Esophageal Cancer via Integrin Alpha 11.	BACKGROUND: As a common disease around the world, esophageal cancer (EC) primarily includes two subclasses: esophageal adenocarcinoma and esophageal squamous cell carcinoma. Mortality has been rising over the years; hence, exploring the mechanism of EC development has become critical. Among the alpha protein kinases, alpha protein kinase 2 (ALPK2) presumably has a connection with EC, but it has never been revealed before. METHODS: In this study, IHC analysis was used for ALPK2 expression quantification in ES tissues. TE-1 and Eca-109, which are both human EC cell lines, were used for in vitro analysis of cell proliferation, migration, apoptosis, and colony formation. RESULTS: ALPK2 was found to have an abundant expression within EC tissues (P < 0.001), as well as in the two selected human EC cell lines (P < 0.05). The data showed that ALPK2 depletion suppressed EC cell proliferation, migration, and colony formation, meanwhile stimulating apoptosis (P < 0.001). The in vivo experiments also displayed inhibitory effects caused by ALPK2 depletion on EC tumorigenesis (P < 0.001). It was further validated that ALPK2 depletion made the phosphorylation of Akt and mTOR, as well as CDK6 and PIK3CA levels downregulated (P < 0.001). Mechanistically, we identified integrin alpha 11 (ITGA11) as a downstream gene of ALPK2 regulating EC. More importantly, we found that ITGA11 elevation promoted cell proliferation and migration and rescued the suppression effects caused by ALPK2 depletion (P < 0.001). CONCLUSIONS: ALPK2 promotes esophageal cancer via integrin its downstream gene alpha 11; ALPK2 can potentially act as a target for the treatment of EC.	esophagus
The prognostic effect of pretreatment 18F-FDG PET/CT metabolic parameters in locally advanced Esophageal Squamous Cell Carcinoma treated with definitive chemoradiotherapy.	INTRODUCTION: In this study, we aimed to examine the relation between pre-treatment 18F-FDG PET/CT metabolic parameters [(including the maximum standard uptake value (SUV(max)), metabolic tumor volume (MTV), and tumor lesion glycolysis (TLG)] and treatment response and survival in locally-advanced Esophageal Squamous Cell Cancer (ESCC) treated with definitive chemoradiotherapy (dCRT). METHODS: A total 76 patients with locally-advanced ESCC who received dCRT between June 2015 and December 2019 were included in this retrospective study. Patients were divided into two groups as complete response (CR) or non-complete response (Non-CR) according to response to treatment. AUC was obtained as 0.749 (p < 0.001) in the ROC curve drawn by MTV for the CR. The MTV value was ≤12 cm(3), with 72.1% sensitivity and 73.0% specificity. RESULTS: Of the 76 patients, 38 (50%) were male and 38 (50%) were female. The median age was 62 (39-84) years. The treatment response in 35 (46%) patients was CR. MTV value was >12cm3 in 41(54%) patients. Median follow-up time was 14.5 months. In patients with MTV>12cm3, median progression-free survival(mPFS) and median overall survival(mOS) were 9 months and 11 months, respectively, whereas mPFS and OS could not be reached in those with MTV≤12 cm3 (p < 0.001 and p < 0.001, respectively). In patients with non-CR, mPFS and mOS were 8 months and 9 months, respectively, whereas mPFS and OS could not be reached in patients with CR (p < 0.001 and p < 0.001, respectively). In multivariate analysis, age (odds ratio [OR], 1.07), ECOG PS (OR, 11.1), and MTV (OR, 4.73) were found to be the factors affecting treatment response. CONCLUSION: In our study, treatment response and MTV were found to be the factors associated with survival in patients treated with dCRT, showing the pre-treatment MTV value as a predictor of treatment response.	esophagus
Mixed neuroendocrine-non-neuroendocrine neoplasm arising from long-segment Barrett's esophagus showing exceptionally aggressive clinical behavior.	BACKGROUND: There is only one report of Barrett's esophagus (BE) with mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN). Herein, for the first time, we present a case with an aggressive esophageal MiNEN, as well as with both primary MiNEN and conventional adenocarcinoma, arising in BE. CASE: A 68-year-old woman had been diagnosed with 0-IIa type adenocarcinoma in the background of long-segment BE, 45 months earlier. She underwent endoscopic submucosal dissection (ESD) and the pathological diagnosis was tubular adenocarcinoma, well-differentiated, with slight submucosal invasion. There was no lymphovascular invasion and the margins were intact. The upper esophagogastroduodenoscopy conducted the year after ESD showed no residual or recurrent cancer. However, she was subsequently followed up at another hospital, and endoscopy was not performed after the second year. She was urgently transported to our hospital due to buttock pain in the ninth month of the fourth year. A computed tomography (CT) of the head showed multiple cerebral metastases and positron emission tomography-CT revealed numerous osseous and nodal involvements. We performed upper endoscopy and detected type 3 esophageal tumor. Multiple biopsy specimens histopathologically contained invasive neoplasm composed of neuroendocrine carcinoma (NEC) and adenocarcinoma, moderately to poorly differentiated. The NEC element showed diffuse proliferation of primitive cancer cells possessing fine-granular cytoplasm and nuclei with prominent nucleoli, whereas the adenocarcinoma component had tubules or nested growth of basophilic cells. Immunohistochemically, the NEC cells were diffusely positive for synaptophysin, with focal expressions of INSM1, chromogranin A and NCAM, whereas the adenocarcinoma cells were mostly negative for these NE markers. The Ki67 index was 90% at the hot spots in both types. The patient died 3.5 months after the biopsy-based histological diagnosis. CONCLUSION: Appropriate therapy according to the guidelines and/or meticulous clinical follow-up based on periodic endoscopy as well as a full physical examination are essential, from a proactive perspective, for early diagnosis of secondary aggressive cancers after ESD.	esophagus
Sarcopenia Determined by Skeletal Muscle Index Predicts Overall Survival, Disease-free Survival, and Postoperative Complications in Resectable Esophageal Cancer: A Systematic Review and Meta-analysis.	BACKGROUND: Sarcopenia has been identified as a prognostic factor among certain types of cancer. In esophageal cancer, patients are at increased risk of malnutrition and sarcopenia, ultimately contributing to poor outcomes. A systematic review was conducted to determine whether sarcopenia, defined by the skeletal muscle index, is predictive of overall survival, disease-free survival, and postoperative complications in resectable esophageal cancer. MATERIALS AND METHODS: A systematic search of MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines up until January 2021. The primary outcome was overall survival; secondary outcomes included disease-free survival, pulmonary complications, and anastomotic leak. RESULTS: Twenty-one studies (4 prospective; 17 retrospective; 3966 patients) were included. Sarcopenia was present in 1940 (48.1%) patients and was associated with lower overall survival [hazard ratio (HR): 1.56; 95% confidence interval (CI): 1.25-1.95; P <0.00001; I2 =71%] and disease-free survival (HR: 1.73; 95% CI: 1.04-2.87; P =0.03; I2 =51%). A decrease in skeletal muscle index, independent of sarcopenia status, was associated with lower overall survival (HR: 1.81; 95% CI: 1.20-2.73; P =0.005; I2 =92%). Sarcopenia was associated with increased odds of pulmonary complications (odds ratio: 1.86; 95% CI: 1.29-2.66; P =0.0008; I2 =41%) and increased odds of anastomotic leak (odds ratio: 1.46; 95% CI: 1.11-1.93; P =0.008; I2 =0%). CONCLUSIONS: Sarcopenia is a predictor of overall survival, disease-free survival, and postoperative complications in patients with resectable esophageal cancer. Studies on the modifiability of sarcopenia in the preoperative period will help determine the utility of nutritional interventions.	esophagus
Neoadjuvant chemotherapy for locally advanced esophageal cancer comparing cisplatin and 5-fluorouracil versus docetaxel plus cisplatin and 5-fluorouracil: a propensity score matching analysis.	BACKGROUND: The standard treatment for locally advanced esophageal cancer is preoperative chemotherapy with cisplatin and 5-fluorouracil (CF), followed by surgery. Although docetaxel plus cisplatin and 5-fluorouracil (DCF) has been reported to have favorable outcomes, no study has compared its therapeutic efficacy to that of standard treatment. This study aimed to compare the therapeutic effects of CF and DCF in the real world by matching patient background factors using propensity scores. METHODS: We retrospectively reviewed the data of 237 patients with esophageal squamous cell carcinoma who underwent esophagectomy between January 2008 and December 2018. Patients were divided into two groups based on the preoperative chemotherapy regimens of CF (79 patients) or DCF (158 patients), and 49 matched pairs were finally analyzed using propensity score matching. Short- and long-term outcomes were compared between groups. RESULTS: After matching, although no significant differences in survival were observed among the groups, patients receiving DCF showed a significantly high histological response (P < 0.001). Subgroup analyses demonstrated that DCF therapy had better overall survival (P = 0.046) and relapse-free survival (P = 0.010) among pathological T3 and T4 cases. Whereas, adverse effects of chemotherapy were more frequent in the DCF group. CONCLUSIONS: Patients receiving DCF had higher pathological response and better survival than those receiving CF, especially in pathological T3 and T4 cases matched using propensity scores. Thus, the DCF regimen might be an effective treatment for locally advanced esophageal cancer. However, the adverse side effects of chemotherapy remain high and should be handled appropriately.	esophagus
[Development and validation of a prognostic model based on SEER data for patients with esophageal carcinoma after esophagectomy].	OBJECTIVE: To develop a nomogram to predict the long-term survival of patients with esophageal cancer following esophagectomy. METHODS: We collected the data of 7215 patients with esophageal carcinoma from the Surveillance, Epidemiology, and End Results (SEER) database during the period from 2004 and 2016. Of these patients, 5052 were allocated to the training cohort and the remaining 2163 patients to the internal validation cohort using bootstrap resampling, with another 435 patients treated in the Department of Cardiothoracic Surgery of Jinling Hospital between 2014 and 2016 serving as the external validation cohort. RESULTS: In the overall cohort, the 1-, 3-, and 5-year cancer-specific mortality rates were 14.6%, 35.7% and 41.6%, respectively. Age (≥80 years vs < 50 years, P < 0.001), gender (male vs female, P < 0.001), tumor site (lower vs middle segment, P=0.013), histology (EAC vs ESCC, P=0.012), tumor grade (poorly vs well differentiated, P < 0.001), TNM stage (Ⅳ vs Ⅰ, P < 0.001), tumor size (> 50 mm vs 0-20 mm, P < 0.001), chemotherapy (yes vs no, P < 0.001), and LNR (> 0.25 vs 0, P < 0.001) were identified as independent risk factors affecting long-term survival of the patients. The nomograms established based on the model for predicting the survival probability of the patients at 1, 3 and 5 years after operation showed a C-index of 0.726 (95% CI: 0.714-0.738) for predicting the overall survival (OS) and of 0.735 (95% CI: 0.727-0.743) for cancer-specific survival (CSS) in the training cohort. In the internal validation cohort, the C-index of the nomograms was 0.752 (95% CI: 0.738-0.76) for OS and 0.804 (95% CI: 0.790-0.817) for CSS, as compared with 0.749 (95% CI: 0.736-0.767) and 0.788 (95%CI: 0.751-0.808), respectively, in the external validation cohort. The nomograms also showed a higher sensitivity than the TNM staging system for predicting long-term prognosis. CONCLUSION: This prognostic model has a high prediction efficiency and can help to identify the high-risk patients with esophageal carcinoma after surgery and serve as a supplement for the current TNM staging system.	esophagus
Long Non-coding RNAs Sponging MicroRNAs With Efficacy in Preclinical In Vivo Models of Esophageal Squamous Cell Cancer.	Esophageal cancer is of two subtypes: Esophageal adenocarcinoma and esophageal squamous cell carcinoma (ESCC). Both are associated with a dismal prognosis. Therefore, the identification of new targets and treatment modalities is an issue of paramount importance. In this review, we focus on long non-coding RNAs (lncRNAs) which have been shown to mediate efficacy in preclinical in vivo models of ESCC by sponging microRNAs. Searching the literature, we identified four lncRNAs which were down-regulated and 23 which were up-regulated in comparison to corresponding normal tissues. The down-regulated lncRNAs lead to up-regulation of oncogenic pathways and down-regulation of tumor suppressors. The up-regulated lncRNAs target transcription factors, transmembrane receptors, cell-cycle related proteins, actin-binding proteins, signaling pathways, enzymes including epigenetic modification factors, cellular transport proteins and other categories. We describe reconstitution and inhibition of function of the corresponding lncRNAs and comment on validation and druggability of the identified targets.	esophagus
Survival benefits from neoadjuvant treatment in gastric cancer: a systematic review and meta-analysis.	BACKGROUND: Surgery is the main treatment option for patients with local gastric cancer. However, surgery alone is usually not sufficient for stomach cancer patients, and combined therapies are recommended for these patients. In recent studies, some preoperative treatments have shown benefits. However, the treatment selection is still uncertain because previous studies failed to obtain a statistically significant difference between preoperative chemotherapy and preoperative chemoradiotherapy. Therefore, we plan to perform a systematic review and meta-analysis to compare the benefits among these preoperative treatments. METHODS/DESIGN: This review includes randomized controlled trials with or without blinding as well as published studies, high-quality unpublished studies, full articles and meeting abstracts with an English context if sufficient results were provided for analysis. Data sources include the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, major relevant international conferences and manual screening of references. Patients with a diagnosis of resectable primary gastric or EGJ adenocarcinoma (stage II or higher) who underwent surgery alone or preoperative treatment followed by surgery and who were pathologically confirmed as proposed by the AJCC 2017 guidelines without age, sex, race, subtypes of adenocarcinoma and molecular pathology limitations will be included. The following three interventions will be included: surgery alone, neoadjuvant chemistry followed by surgery and neoadjuvant chemoradiotherapy followed by surgery. All-cause mortality, overall survival (OS, the time interval from diagnosis to death) and/or progression-free survival (PFS, the time interval from diagnosis to disease progression or death from any cause) will be defined as major results of concern. The clinical and pathological response rate (according to RECIST and tumour regression score), R0 resection rate, quality of life and grade 3 or above adverse events (according to the National Cancer Institute Common Terminology Criteria for Adverse Events, NCI-CTCAE) will be defined as the secondary outcomes. DISCUSSION: The aim of this systematic review is to compare the benefits of different preoperative treatments for patients with locoregional stomach cancer. This systematic review will improve the understanding of the relative efficacy of these treatment options by providing the latest evidence on the efficacy of various treatment options in the management of gastric cancer patients and may guide clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD4202123718.	esophagus
Tislelizumab versus chemotherapy as second-line treatment of advanced or metastatic esophageal squamous cell carcinoma (RATIONALE 302): impact on health-related quality of life.	BACKGROUND: RATIONALE 302 (NCT03430843) an open-label, phase III study of second-line treatment of advanced/metastatic esophageal squamous cell carcinoma (ESCC), reported that tislelizumab, relative to investigator-chosen chemotherapy (ICC), was associated with improvements in overall survival and a favorable safety profile. This study assessed the health-related quality of life (HRQoL) and ESCC-related symptoms of patients in RATIONALE 302. METHODS: Adults with advanced/metastatic ESCC whose disease progressed following prior systemic therapy were randomized 1 : 1 to receive either tislelizumab or ICC (paclitaxel, docetaxel, or irinotecan). HRQoL was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items (EORTC QLQ-C30), the EORTC Quality of Life Questionnaire Oesophageal Cancer Module 18 items (QLQ-OES18), and the EuroQoL Five-Dimensions Five-Levels (EQ-5D-5L) visual analogue scale. Mixed effect modeling for repeated measurements examined changes from baseline to weeks 12 and 18. The Kaplan-Meier method was used to examine time to deterioration. RESULTS: Overall, 512 patients were randomized to tislelizumab (n = 256) or ICC (n = 256). The tislelizumab arm maintained QLQ-C30 global health status/quality whereas the ICC arm worsened at week 12 {difference in least square (LS) mean change: 5.8 [95% confidence interval (CI): 2.0-9.5], P = 0.0028} and week 18 [difference in LS mean change: 8.1 (95% CI: 3.4-12.8), P = 0.0008]. Physical functioning (week 18) and fatigue (weeks 12 and 18) worsened less in the tislelizumab compared with the ICC arm. The tislelizumab arm improved in reflux symptoms, whereas the ICC worsened at week 12 [difference in LS mean change: -4.1 (95% CI: -7.6 to -0.6), P = 0.0229]. The visual analogue scale remained consistent in the tislelizumab arm whereas it worsened in the ICC arm. The hazard of time to deterioration was lower in tislelizumab patients compared with ICC for physical functioning and reflux. CONCLUSIONS: HRQoL, including fatigue symptoms and physical functioning, was maintained in patients with advanced or metastatic ESCC receiving tislelizumab compared with ICC-treated patients. These results provide additional support for the benefits of tislelizumab in this patient population.	esophagus