crossing96/oncoscreening huggingface dataset:
Genetic variant in miR-17-92 cluster binding sites is associated with esophageal squamous cell carcinoma risk in Chinese population.	BACKGROUND: Single nucleotide polymorphisms (SNPs) located in microRNA (miRNA) binding sites can affect the interactions between miRNAs and target genes, which is related to cancer susceptibility and tumorigenesis. However, the association between SNPs located in miR-17-92 cluster binding sites and ESCC risk remains unclear. Therefore, we aimed to explore the relationship between polymorphisms in miR-17-92 cluster binding sites and ESCC susceptibility. METHODS: Six SNPs in the binding sites of miR-17-92 cluster were selected using bioinformatics databases, and their association with ESCC risk was investigated in a case-control study (including 488 cases and 512 controls) based on the population from high incidence areas of ESCC in China. We evaluated the SNP-SNP and SNP-smoking interactions using generalized multifactor dimensionality reduction (GMDR). Moreover, the expression of the miR-17-92 cluster and its target genes was determined in ESCC and adjacent normal tissues by quantitative real-time polymerase chain reaction (qRT-PCR). The dual-luciferase reporter assay was conducted to verify the effect of SNPs on the binding affinity between miRNAs and target genes. RESULTS: We found that the SNP rs1804506 C > T had a significant association with the decreased ESCC risk. The SNP rs1804506 T allele was associated with a significantly decreased risk of ESCC in the additive model (OR = 0.817, 95% CI = 0.681-0.981, P = 0.030). The rs1804506 T allele had more striking effects on reducing ESCC risk in older individuals, female or non-smoker subgroups. We also found a significant interaction effect between rs1366600 and smoking by GMDR methods (P = 0.011). Additionally, the expression levels of miR-19a-3p and TGFBR3 were significantly downregulated in ESCC tissues compared with normal tissues, and the carriers of rs1804506 TT genotype had lower expression level of TGFBR3 than those of rs1804506 CC/CT genotype. Following dual-luciferase reporter assay showed that the rs1804506 T allele reduced the binding of miR-19a-3p and TGFBR3 3'-UTR. CONCLUSIONS: Our findings suggest that the rs1804506 polymorphism in miR-17-92 cluster binding sites contributes to the susceptibility of ESCC, which might provide new clues and scientific evidence for the etiology and biomarkers for the prevention and treatment of ESCC.	esophagus
Identification of the miRNA-mRNA regulatory network associated with radiosensitivity in esophageal cancer based on integrative analysis of the TCGA and GEO data.	BACKGROUND: The current study set out to identify the miRNA-mRNA regulatory networks that influence the radiosensitivity in esophageal cancer based on the The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. METHODS: Firstly, esophageal cancer-related miRNA-seq and mRNA-seq data were retrieved from the TCGA database, and the mRNA dataset of esophageal cancer radiotherapy was downloaded from the GEO database to analyze the differential expressed miRNAs (DEmiRNAs) and mRNAs (DEmRNAs) in radiosensitive and radioresistant samples, followed by the construction of the miRNA-mRNA regulatory network and Gene Ontology and KEGG enrichment analysis. Additionally, a prognostic risk model was constructed, and its accuracy was evaluated by means of receiver operating characteristic analysis. RESULTS: A total of 125 DEmiRNAs and 42 DEmRNAs were closely related to the radiosensitivity in patients with esophageal cancer. Based on 47 miRNA-mRNA interactions, including 21 miRNAs and 21 mRNAs, the miRNA-mRNA regulatory network was constructed. The prognostic risk model based on 2 miRNAs (miR-132-3p and miR-576-5p) and 4 mRNAs (CAND1, ZDHHC23, AHR, and MTMR4) could accurately predict the prognosis of esophageal cancer patients. Finally, it was verified that miR-132-3p/CAND1/ZDHHC23 and miR-576-5p/AHR could affect the radiosensitivity in esophageal cancer. CONCLUSION: Our study demonstrated that miR-132-3p/CAND1/ZDHHC23 and miR-576-5p/AHR were critical molecular pathways related to the radiosensitivity of esophageal cancer.	esophagus
Integrin beta1 (ITGB1) as a prognostic marker in esophageal adenocarcinoma.	Today, individual prognosis in patients with adenocarcinoma of the esophagus (EAC) is based on post-surgical TNM staging and valid biomarkers are still not implemented. Integrin beta1 (ITGB1) is widely expressed in epithelial cells and promotes cell adhesion and growth. Its impact on tumor progression was described for different tumor entities before, data on its function as a potential biomarker in EAC is not available. Aim of the study is to evaluate the expression level of ITGB1 in a large collective of EAC and its impact on patients´ prognosis. 640 patients with esophageal adenocarcinoma were analyzed immunohistochemically for ITGB1. The data was correlated with long term outcome, clinical, pathological and molecular data (TP53, HER2/neu, c-myc, GATA6, PIK3CA and KRAS). Of 640 patients to be analyzed, 127 (19.8%) showed expression of ITGB1. ITGB1 expression was associated with lymph node metastasis, expression of integrin alphaV and KRAS mutation status. Patients with high ITGB1 expression showed impaired overall survival (22.5 months (95% CI 15.3-29.7 months), vs. 34.1 months (95% CI 25.3-42.4 months), P = 0.024). This effect was particularly evident in the group of patients undergoing primary surgery without prior neoadjuvant therapy (10.2 months (95% CI 1.9-41.7 months) vs. 31.4 months (95% CI 21.1-144.2 months, P = 0.008). ITGB1 was also an independent prognostic marker in multivariable analysis (HR 1.696 (95% CI 1.084-2.653, P = 0.021) in patients that underwent primary surgery. We demonstrate for the first time the prognostic significance of ITGB1 expression in a large EAC patient population.	esophagus
Predictive Factors of Febrile Neutropenia After Primary Prophylactic Pegfilgrastim With DCF Chemotherapy for Esophageal Cancer.	BACKGROUND/AIM: We investigated the predictive factors of febrile neutropenia (FN) after the administration of pegfilgrastim as primary prophylaxis in patients with esophageal cancer who received neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF) to support the appropriate management of FN. We evaluated changes in neutrophil counts and relative dose intensity (RDI) after the incidence of FN. PATIENTS AND METHODS: This retrospective study involved 122 patients with esophageal cancer who were treated with DCF and pegfilgrastim at Showa University Hospital, Japan, between April 2016 and August 2021. The primary outcome was FN incidence after cycle 1 of DCF chemotherapy. The significant independent factors associated with FN incidence were selected using the multivariate analysis. Changes in neutrophil counts and RDI were compared between the FN and non-FN groups. RESULTS: One-hundred patients were included in the analysis. The incidence of FN in cycle 1 was 21%. In the multivariate analysis, geriatric nutritional risk index (GNRI) <92 [odds ratio (OR)=13.162, p<0.001] and combination of platelet and neutrophil-to-lymphocyte ratio (COP-NLR) score of 0 (OR=4.619, p=0.012) were independent predictors of FN. The neutrophil count on day 7-10 and RDI in the FN group were lower than those in the non-FN group (all p<0.05). CONCLUSION: GNRI <92 and COP-NLR score of 0 are important indicators to predict patients at high risk of DCF chemotherapy-induced FN. Furthermore, FN incidence after pegfilgrastim administration had a strong effect on delayed neutrophil recovery and reduced RDI.	esophagus
LncRNA BBOX1-AS1 targets miR-361-3p/COL1A1 axis to drive the progression of oesophageal carcinoma.	BACKGROUND: Oesophageal carcinoma (EC) is one of the types of prevalent malignant cancer in the globe. Many researchers reported the vital role played by long-coding RNAs in EC. In the current research, we investigated the mechanisms of the action of lncRNA BBOX1-AS1 in EC progression. METHODS: In EC tissues and EC cells, the expression levels of miR-361-3p along with COL1A1 and BBOX1-AS1 were detected through RT-qPCR or western blotting. MiR-361-3p interactions with BBOX1-AS1 or COL1A1 were verified through Luciferase reporter and RIP tests. Loss of function combined with caspase-3 activity, CCK-8 and Transwell assays was performed to investigate cell apoptosis, proliferation and migration, respectively. Knockdown of BBOX1-AS1 was used for evaluating BBOX1-AS1 effects on tumour development in vivo. RESULTS: BBOX1-AS1 was remarkably elevated in EC tissues and cells. In addition, the silencing of BBOX1-AS1 attenuated the cell viability, cell migration and enhanced cell apoptosis of EC, as well as suppressed EC tumour formation in vivo. Moreover, BBOX1-AS1 was found to be a sponge of miR-361-3p, which downregulated miR-361-3p expression. MiR-361-3p inhibitor rescued the anti-tumour effect of BBOX1-AS1 knockdown on the progression of EC. Furthermore, we discovered that miR-361-3p specially bound to COL1A1 3'UTR and downregulated COL1A1 and COL1A1 reduction declined the promoting effect of silencing miR-361-3p on EC cell malignant phenotypes. CONCLUSION: BBOX1-AS1 facilitated the EC development and malignancy via miR-361-3p/COL1A1 axis, indicating BBOX1-AS1 could be a novel therapy target for the diagnostic of EC.	esophagus
SOURCE beyond first-line: A survival prediction model for patients with metastatic esophagogastric adenocarcinoma after failure of first-line palliative systemic therapy.	Prior models have been developed to predict survival for patients with esophagogastric cancer undergoing curative treatment or first-line chemotherapy (SOURCE models). Comprehensive clinical prediction models for patients with esophagogastric cancer who will receive second-line chemotherapy or best supportive care are currently lacking. The aim of our study was to develop and internally validate a new clinical prediction model, called SOURCE beyond first-line, for survival of patients with metastatic esophagogastric adenocarcinoma after failure of first-line palliative systemic therapy. Patients with unresectable or metastatic esophageal or gastric adenocarcinoma (2015-2017) who received first-line systemic therapy (N = 1067) were selected from the Netherlands Cancer Registry. Patient, tumor and treatment characteristics at primary diagnosis and at progression of disease were used to develop the model. A Cox proportional hazards regression model was developed through forward and backward selection using Akaike's Information Criterion. The model was internally validated through 10-fold cross-validations to assess performance. Model discrimination (C-index) and calibration (slope and intercept) were used to evaluate performance of the complete and cross-validated models. The final model consisted of 11 patient tumor and treatment characteristics. The C-index was 0.75 (0.73-0.78), calibration slope 1.01 (1.00-1.01) and calibration intercept 0.01 (0.01-0.02). Internal cross-validation of the model showed that the model performed adequately on unseen data: C-index was 0.79 (0.77-0.82), calibration slope 0.93 (0.85-1.01) and calibration intercept 0.02 (-0.01 to 0.06). The SOURCE beyond first-line model predicted survival with fair discriminatory ability and good calibration.	esophagus
Using Data Mining and Association Rules for Early Diagnosis of Esophageal Cancer.	From 17,000 new cases of esophageal cancer worldwide during last year, 16,000 proved to be fatal. Late or incorrect diagnosis of esophageal cancer cases increases its fatality rate. Today, a data-mining technique can predict the course of the disease with the help of an upto-date technology. With this knowledge, we can reduce esophageal cancer mortality. This study aims to find an association between general characteristics, screening tests, and esophageal cancer based on raw data from the Cancer Research Center within-person interviews, using data mining and classification techniques on mortality. The 5-year medical records of 512 esophageal cancer patients and those with problems related to this cancer, with 50 functional characteristics, were included in this model. In order to provide a prognostic and rule discovery model for esophageal cancer suffering, we used preprocessing EM Algorithm. After accurate identification of the data, WEKA Software tools and Java programming language was used to create Association Rule Classifier and Apriori algorithm for the associated rule discovery. We created 6 significant rules of the association for classification generated by rule miner with 95% and 91% confidence based on screening tests and general attributes, respectively. These substantial rules showed significant association between age, history of medication, smoking, gender, carcinoembryonic antigen (CEA), creatinine, WBCs, and Platelets. The findings of this study can be used as a clue for physicians to consider patients with these characteristics as people who are more likely to develop esophageal cancer and help them for early diagnosis of patients. Keywords:Data mining, esophageal cancer, association rule, healthcare.	esophagus
HPV 16 E6 promotes growth and metastasis of esophageal squamous cell carcinoma cells in vitro.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies worldwide. Increasing evidence suggests that human papillomavirus (HPV) infection may be associated with the etiology of ESCC. However, the precise role of HPV in ESCC remains unclear. METHODS AND RESULTS: Proliferation and apoptosis of ESCC cells upon infection with HPV16 E6 were detected using CCK-8 assays and Western blot analyses. The migration rate was measured with a wound healing assay, and a Transwell Matrigel invasion assay was used to detect the invasive ability. RT-qPCR was performed to detect the expression of E6AP, p53, and miR-34a. The proliferation rates were significantly higher in HPV16E6-transfected cell groups compared with the negative control groups. Bax protein expression was downregulated in HPV16E6-treated groups compared to the controls. The wound healing and Transwell Matrigel invasion assays indicated that HPV16 E6 infection could increase ESCC cell migration and invasion. Furthermore, E6AP, p53 and miR-34a expression were decreased in HPV16 E6-transfected cell lines. CONCLUSION: Our results not only provide evidence that HPV16 E6 promotes cell proliferation, migration, and invasion in ESCC, but also suggests a correlation between HPV infection and E6AP, p53 and miR-34a expression. Consequently, HPV16 E6 may play an important role in ESCC development.	esophagus
Impacts of neoadjuvant chemoradiotherapy on the immune landscape of esophageal squamous cell carcinoma.	BACKGROUND: Neoadjuvant chemoradiotherapy (neoCRT) followed by surgery is the most common approach for locally advanced resectable esophageal squamous cell carcinoma (ESCC) patients. How neoCRT impacts ESCC tumor immune microenvironment (TIME) has not been fully understood. METHODS: Single-cell RNA sequencing (scRNA-seq) was conducted to examine the neoCRT-driven cellular and molecular dynamics in 8 pre- and 7 post-neoCRT ESCC samples from 8 male patients. FINDINGS: scRNA-seq data of about 112,000 cells were obtained. Expression programs of cell cycle, epithelium development, immune response, and extracellular structure in pre-treatment tumor cells were related to neoCRT response. Spearman correlation between CD8(+) T cells' cytotoxicity and expression of checkpoint molecules was prominent in pre-neoCRT intermediate activated/exhausted CD8(+) T cells. NeoCRT increased CD8(+) T cells' infiltration but promoted their exhaustion in both major and minor responders. NeoCRT promoted differentiation of Th but demoted that of Treg cells in major responders. Maturation of cDC1s and expression of M2 macrophage markers increased while the number of cDC2s decreased after neoCRT. Higher activities of immune-related pathways in pre-neoCRT CD8(+) T cells and macrophages, as well as a pronounced decrease of them after neoCRT, correlated with better neoCRT response. Interactions between intermediate activated/exhausted CD8(+) T and macrophages, cDC1s, and LAMP3(+) cDCs decreased after neoCRT. INTERPRETATION: Our comprehensive picture of the neoCRT-related immune changes provides deeper insights into immunological mechanisms associated with ESCC response to neoCRT, which may aid in future development of immune-strategies for improving ESCC treatment. FUNDING: This work was supported by the National Natural Science Foundation of China (82072607).	esophagus
Risk factors for refractory enterocutaneous fistula following button jejunostomy removal and its treatment using a novel extraperitoneal approach in patients with oesophageal cancer: a retrospective cohort study.	BACKGROUND: Enterocutaneous fistula after removal of the jejunostomy tube leads to multiple problems, such as cosmetic problems, decreased quality of life, electrolyte imbalances, infectious complications, and increased medical costs. However, the risk factors for refractory enterocutaneous fistula (REF) after button jejunostomy removal remain unclear. Therefore, in this study, we assessed the risk factors for REF after button jejunostomy removal in patients with oesophageal cancer and reported the surgical outcomes of the novel extraperitoneal approach (EPA) for REF closure. METHODS: This retrospective cohort study included 47 patients who underwent button jejunostomy removal after oesophagectomy for oesophageal cancer. We assessed the risk factors for REF in these patients and reported the surgical outcomes of the novel EPA for REF closure at the International University of Health and Welfare Hospital between March 2013 and October 2021. The primary endpoint was defined as the occurrence of REF after removal of the button jejunostomy, which was assessed using a maintained database. The risk factors and outcomes of the EPA for REF closure were retrospectively analysed. RESULTS: REFs occurred in 15 (31.9%) patients. In the univariate analysis, REF was significantly more common in patients with albumin level < 4.0 g/dL (p = 0.026), duration > 12 months for button jejunostomy removal (p = 0.003), and with a fistula < 15.0 mm (p = 0.002). The multivariate analysis revealed that a duration > 12 months for button jejunostomy removal (odds ratio [OR]: 7.15; 95% confidence interval [CI]: 1.38-36.8; p = 0.019) and fistula < 15.0 mm (OR: 8.08; 95% CI: 1.50-43.6; p = 0.002) were independent risk factors for REF. EPA for REF closure was performed in 15 patients. The technical success rate of EPA was 88.2%. Of the 15 EPA procedures, fistula closure was achieved in 12 (80.0%). The complications of EPA (11.7%) were major leakages (n = 3) and for two of them, EPA procedure was re-performed, and closure of the fistula was finally achieved. CONCLUSION: This study suggested that duration > 12 months for button jejunostomy removal and fistula < 15.0 mm are the independent risk factors for REF after button jejunostomy removal. EPA for REF closure is a novel, simple, and useful surgical option for patients with REF after oesophagectomy.	esophagus
Improvement of postoperative quality of life in patients with esophageal squamous cell carcinoma: does tea consumption have a role?	BACKGROUND: To investigate the effect of tea consumption on the improvement of postoperative quality of life in male patients with esophageal squamous cell carcinoma (ESCC). METHODS: The quality of life information of 290 male patients with ESCC was collected. The time to deterioration and the number of events in each area of quality of life was calculated by time-to-deterioration (TTD) model. The association between postoperative tea drinking and postoperative quality of life in male ESCC patients was investigated using the Cox proportional risk model. RESULTS: Postoperative tea-drinking patients experienced delayed TTD in multiple domains, including general health, physical, role, emotional, and cognitive function, fatigue, nausea and vomiting, dyspnea, loss of appetite, constipation, diarrhea, eating problems, difficulty swallowing, choking while swallowing saliva, dry mouth, taste difficulties, coughing, and speech problems. The multivariate Cox regression analysis showed that drinking tea after surgery improved quality of life, including physical function (HR = 0.722, 95% CI: 0.559-0.933), role function (HR = 0.740, 95% CI: 0.557-0.983), eating problems (HR = 0.718, 95% CI: 0.537-0.960), odynophagia (HR = 0.682, 95% CI: 0.492-0.945), trouble swallowing saliva (HR = 0.624, 95% CI: 0.444-0.877), coughing (HR = 0.627, 95% CI: 0.442-0.889) and speech problems (HR = 0.631, 95% CI: 0.441-0.903). Furthermore, the improvement was more significant in patients who drank tea before surgery and continued to drink tea after surgery. CONCLUSIONS: Postoperative tea drinking had a positive effect on delay in clinical deterioration and improvements in multiple functions and symptoms associated with ESCC in men.	esophagus
Influences of intratumoral heterogeneity on assessment of tumor microenvironment in esophageal squamous cell carcinoma.	The intratumoral heterogeneity (ITH) of the tumor microenvironment (TME) has yet to be addressed in esophageal squamous cell carcinoma (ESCC). Here, we studied the ITH of CD8 and PD-L1 status in ESCC, and examined the potential of the tumor surface for representing the TME. In total, 67 surgically resected clinical Stage II ESCC specimens were analyzed. The CD8-cell density, PD-L1 tumor proportion score (TPS), and combined positive score (CPS) were calculated in three (superficial, middle, and deep) areas of each specimen. ITH was quantified by distance-standardized coefficient variations of the three values. The CD8 and PD-L1 status of each area was dichotomized and tumor-surface capabilities for predicting the entire tumor status were estimated. Variables were compared according to the presence of neoadjuvant chemotherapy (NAC). The ITH, especially PD-L1 heterogeneity, differed markedly among specimens. The concordance rates of CD8 and PD-L1 (CPS and TPS) status among the three different areas were 71.6%, 74.6%, and 73.1%, respectively. The sensitivity and the specificity of the tumor surface for predicting the CD8 status of the whole tumor were high, especially in the NAC- group (both 1.0). The tumor surface also showed high capabilities for representing the whole PD-L1 status, while yielding moderate positive predictive values (0.70). The ITH degrees and predictive capabilities did not differ according to NAC. Taken together, the ITH of CD8 and PD-L1 differed among ESCC specimens, while not being markedly affected by NAC. The use of a biopsy specimen from the tumor surface might be feasible for TME evaluation.	esophagus
Predicting Factors for a Favorable Pathologic Response to Neoadjuvant Therapy in Esophageal Cancer.	BACKGROUND: Favorable pathologic response(FPR) is a significant predictor for improved survival following Neoadjuvant therapy(NAT) in esophageal and gastroesophageal cancer(GEJ). Preoperative prediction of FPR could modify treatment plans. No reliable method for predicting FPR exists. We sought to identify preoperative predicting factors for FPR. MATERIALS AND METHODS: Retrospective analysis of patients with esophageal and GEJ cancer who underwent esophagectomy following (NAT). Univariate and multivariate analysis was used to identify preoperative predicting factors for FPR. A comparison of Tumor Regression Grade(TRG) was used to assess treatment response on overall survival(OS). RESULTS: Out of 121 patients, 82(67.8%) had neoadjuvant chemoradiation. FPR was observed in 60(49.6%). Female sex, Radiation therapy(RT), squamous cell carcinoma(SCC), lack of signet ring feature, and FDG avidity posttreatment were associated with FPR on univariate analysis. RT and SCC were associated with FPR (OR=3.9 and 4.0, respectively) on multivariate analysis. OS was lower among patients who did not achieve FPR to NAT(P=0.027). CONCLUSIONS: FPR is a predictor of improved OS. SCC and radiation therapy-based protocol were identified as major prediction factors of FPR in patients with esophageal and GEJ cancers.	esophagus