crossing96/oncoscreening huggingface dataset:
CLDN1 induces autophagy to promote proliferation and metastasis of esophageal squamous carcinoma through AMPK/STAT1/ULK1 signaling.	Tight junction is a structural constitution in cell-cell adhesion and play an important role in the maintenance of permeability and integrity of normal epithelial cell barrier. The protein encoded by Claudin 1 (CLDN1), a member of the claudin family, is an integral membrane protein and a component of tight junction strands. CLDN1 has been proved to regulate the proliferation and metastasis of multiple tumors, but little is known about its role in esophageal squamous cell carcinoma (ESCC). Here, we found that CLDN1 was aberrantly increased in ESCC tissues and cell lines, and mainly distributed in the nucleus of tumor cells. Furthermore, we confirmed that CLDN1 promoted the proliferation and metastasis of ESCC by triggering autophagy both in vitro and in vivo. Mechanically, we validated that CLDN1-induced autophagy via increasing Unc-51 like autophagy activating kinase 1 (ULK1) expression through AMP-activated protein kinase (AMPK)/signal transducer and activator of transcription 1 (STAT1) signaling pathway in ESCC cells. Taken together, our findings demonstrated that aberrant expression and distribution of CLDN1 promoted the proliferation and metastasis of esophageal squamous carcinoma by triggering autophagy through AMPK/STAT1/ULK1 signaling pathway.	esophagus
Long noncoding RNA PANDA promotes esophageal squamous carcinoma cell progress by dissociating from NF-YA but interact with SAFA.	Esophageal squamous cell carcinoma (ESCC) is one of the major global health problems, especially in Asia. Long non-coding RNAs (lncRNAs) have been increasingly identified and characterized in almost every aspect of biology, especially in cancer biology. This research desires to explore the regulatory mechanism of lncRNA PANDA (PANDA) on ESCC process. Quantitative real-time PCR (qRT-PCR) was carried out to detect the PANDA expression, which was up-regulated in matched cancerous tissues and adjacent noncancerous tissues from 134 patients and 9 ESCC cell lines. Higher expression of PANDA in ESCC tissues was associated with TNM stage, advanced clinical stage, and shorter overall survival of ESCC patients by MTT, EDU, colony formation assay and ﬂow cytometry in KYSE180 and KYSE450 cells. Exogenous down-regulation of PANDA expression signiﬁcantly suppressed ESCC cells proliferation and colony formation by arresting G1-S checkpoint transition in vitro, and retarded the development of tumors in vivo. Meanwhile, qRT-PCR and western blot assays showed that depletion of PANDA reduced E2F1, cyclinD1, cyclinD2, cyclinE1 and Bcl-2 expression. RIP showed the interaction between PANDA and NF-YA or SAFA. Our findings suggested that, PANDA drifted away from NF-YA to promote the expression of NF-YA-E2F1 co-regulated proliferation-promoting genes, and to limit the cell apoptosis. In addition, PANDA binds SAFA to switch on the tumor proliferation program through CyclinD1/2-Cyclin E1 and Bcl-2 pathways. PANDA could serve as a potential prognostic biomarker and therapeutic target for ESCC.	esophagus
Cancer of the oesophagus and lymph nodes management in the neoadjuvant or definitive radiochemotherapy setting.	Despite representing a 1% of diagnosed cancer cases in the USA and up to 5% in eastern Asia and Africa, oesophageal cancer still holds numerous questions concerning the best therapeutic management. For squamous cell carcinoma, while radiochemotherapy has proven itself to be the gold standard as part of the trimodality or alone as a definitive treatment, radiotherapy modalities are still debated especially regarding lymph node irradiation. Involved nodes irradiation was developed with the aim of maintaining clinical outcomes and enhancing quality of life but lacks grade 1 evidence. In this article, we aim to summarize the state of art regarding lymph node irradiation, discuss the impact of target definition, delivery techniques, concomitant treatment and the perspectives. Being highly connected to the lymph vessels, lymphatic metastases are frequent and can locate from the neck to the coeliac area with each node having a different prognostic significance. Regarding the comparison between elective nodal irradiation and involved nodes irradiation, evidence-based medicine mostly relies on retrospective studies. Pooled, it suggests similar clinical outcomes with lower acute toxicities in favour of involved nodes irradiation. However, delivery techniques, doses and concomitant treatment were not consensual. Studies are ongoing evaluating the impact of radiation delivery techniques and the choice of concomitant treatment, i.e. immunotherapy. Modern techniques of imaging, radiation therapy progressing each day and alternative treatment modalities being tested, the need of randomized controlled trials has never been so high. Elective nodal irradiation should remain the standard of care while phase 3 trials explore the safety of involved nodal irradiation.	esophagus
Second primary malignancy in patients with esophageal adenocarcinoma and squamous cell carcinoma.	There have been no studies on implementing effective screening models for esophageal adenocarcinoma and squamous cell carcinoma survivors. We used a proportional subdistribution hazards model to estimate second primary malignancy risks among patients with esophageal adenocarcinoma and squamous cell carcinoma. We validated models using a bootstrap cross-validation method and performed decision curve analysis to evaluate their clinical utility. Age group and SEER historic stage were significantly associated with second primary malignancy risk after diagnosis of esophageal adenocarcinoma and squamous cell carcinoma. Saving positive lymph nodes and distant metastasis were significant factors in the adenocarcinoma group, and marital status, tumor location, and chemotherapy were significant factors in the squamous cell carcinoma group. Calibration plots show good concordance between predicted and actual outcomes except in high-probability areas for the risk of a second primary malignancy in patients with esophageal squamous cell carcinoma. Discrimination performances of the Fine-Gray models were evaluated using c-indices, which were 0.691 and 0.662 for second primary malignancies in patients with esophageal adenocarcinoma and squamous cell carcinoma, respectively. Decision curve analysis yielded a range of threshold probabilities (0.020-0.177 and 0.021-0.133 for patients with esophageal adenocarcinoma and squamous cell carcinoma, respectively) at which the clinical net benefit of the risk model was larger than those of hypothetical all-screening and no-screening scenarios. Our nomograms enable selection of patient populations at high risk for a second primary malignancy and thus will facilitate the design of prevention trials for affected populations.	esophagus
Identification of microRNAs as novel biomarkers for esophageal squamous cell carcinoma: a study based on The Cancer Genome Atlas (TCGA) and bioinformatics.	BACKGROUND: MicroRNAs (miRNAs) have played important roles in the regulation of gene expression in many cancers, but their roles in esophageal squamous cell carcinoma (ESCC) are still unclear. The aim of this study was to determine the potential ESCC-specific key miRNAs from a large sample dataset in The Cancer Genome Atlas (TCGA). METHODS: Integrative bioinformatics analysis was used to identify key ESCC-specific miRNAs related to the ESCC patients' tumor histological grade and lymphatic metastasis from TCGA. Next, these key miRNA potential gene regulatory functions and relationships with ESCC patients' clinical characteristics and overall survival were analyzed. Finally, three key miRNAs were selected randomly and quantificational real-time polymerase chain reaction (qRT-PCR) was used to validate in 51 newly diagnosed ESCC patients' tissues samples (collected from Nov. 2017 to Feb. 2019, in Wuwei, China) whether the bioinformatics analyses results were reliable and valid. Two-tailed Student's t test, Pearson Chi-squared test and Kaplan-Meier survival analysis were used in this study. RESULTS: Thirty-five ESCC-specific miRNAs from TCGA database were investigated (fold-change > 2.0, P < 0.05), and 28 participated in the miRNAs-mRNAs co-expression network construction, while 17 were related with ESCC patients' tumor histological grade, TNM stage, and lymphatic metastasis (P < 0.05). Meanwhile, six miRNAs (including miR-200b-3p, miR-31-5p, miR-15b-5p, miR-141-3p, miR-135b-5p, and miR-195-5p) were correlated with overall survival of ESCC patients (log-rank, P < 0.05). MiR-135b-5p, miR-15b-5p, and miR-195-5p were selected for verification of the expression levels in 51 ESCC patients' tissue samples by using qRT-PCR. We found that the fold-changes between qRT-PCR and TCGA were completely consistent. The results also suggested that miR-135b-5p, miR-15b-5p, and miR-195-5p were significantly correlated with tumor differentiation degrees (P < 0.05), miR-195-5p was significantly correlated with tumor TNM stage (P < 0.05), and miR-135b-5p was significantly correlated with lymph-node metastasis (P < 0.05). MiR-135b-5p, miR-15b-5p, and miR-195-5p expression levels, ESCC patient clinical features association analysis results and the aforementioned TCGA bioinformatics analyses were similar. CONCLUSION: This study identified key ESCC-related miRNAs. The key miRNAs are worthy of further investigation as potential novel biomarkers for diagnosis, classification, and prognosis of ESCC.	esophagus
Benign gastrobronchial fistula following oesophagectomy in a patient presenting with respiratory failure.	Benign gastrobronchial fistula (GBF) is a rare but potentially life-threatening complication of oesophagectomy for malignancy. We present a case of GBF post Ivor-Lewis surgery manifesting as pulmonary sepsis and type II respiratory failure. Clues to the diagnosis were persistent hypercapnia despite high minute ventilation, aspiration of gastric content through the endotracheal tube and accumulation of air in the nasogastric drainage bag. Flexible bronchoscopy confirmed the diagnosis. Surgical exploration identified necrosis of the proximal stomach as causative factor. Despite reconstruction of the oesophagogastric anastomosis and interposition of an intercostal muscle flap, the patient developed a new episode of type II respiratory failure. Bronchoscopy revealed in situ recurrence of the fistula. Patency of the fistula was proven through application of methylene blue with subsequent gastroscopy. A conservative, symptom-based, management was conducted. The patient died 6 hours later.	esophagus
Integrative genomics analysis of hub genes and their relationship with prognosis and signaling pathways in esophageal squamous cell carcinoma.	The main purpose of the present study was to recognize the integrative genomics analysis of hub genes and their relationship with prognosis and signaling pathways in esophageal squamous cell carcinoma (ESCC). The mRNA gene expression profile data of GSE38129 were downloaded from the Gene Expression Omnibus database, which included 30 ESCC and 30 normal tissue samples. The differentially expressed genes (DEGs) between ESCC and normal samples were identified using the GEO2R tool. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify the functions and related pathways of the genes. The protein‑protein interaction (PPI) network of these DEGs was constructed with the Search Tool for the Retrieval of Interacting Genes and visualized with a molecular complex detection plug‑in via Cytoscape. The top five important modules were selected from the PPI network. A total of 928 DEGs, including ephrin‑A1 (EFNA1), collagen type IV α1 (COL4A1),  C‑X‑C chemokine receptor 2 (CXCR2), adrenoreceptor β2 (ADRB2), P2RY14, BUB1B, cyclin A2 (CCNA2), checkpoint kinase 1 (CHEK1), TTK, pituitary tumor transforming gene 1 (PTTG1) and COL5A1, including 498 upregulated genes, were mainly enriched in the 'cell cycle', 'DNA replication' and 'mitotic nuclear division', whereas 430 downregulated genes were enriched in 'oxidation‑reduction process', 'xenobiotic metabolic process' and 'cell‑cell adhesion'. The KEGG analysis revealed that 'ECM‑receptor interaction', 'cell cycle' and 'p53 signaling pathway' were the most relevant pathways. According to the degree of connectivity and adjusted P‑value, eight core genes were selected, among which those with the highest correlation were CHEK1, BUB1B, PTTG1, COL4A1 and CXCR2. Gene Expression Profiling Interactive Analysis in The Cancer Genome Atlas database for overall survival (OS) was applied among these genes and revealed that EFNA1 and COL4A1 were significantly associated with a short OS in 182 patients. Immunohistochemical results revealed that the expression of PTTG1 in esophageal carcinoma tissues was higher than that in normal tissues. Therefore, these genes may serve as crucial predictors for the prognosis of ESCC.	esophagus
Prognostic Value of Combined Analysis of CTLA-4 and PLR in Esophageal Squamous Cell Carcinoma (ESCC) Patients.	OBJECTIVE: The purpose of this study was to evaluate the prognostic role of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) expression level and the platelet lymphocyte ratio (PLR) level in esophageal squamous cell carcinoma (ESCC) patients. METHODS: 84 ESCC patients who received surgical treatment in our hospital were enrolled in the study. The correlation of each biomarker's level with ESCC patients' clinicopathological characteristics and overall survival (OS) was assessed. RESULTS: The elevated expression rate of T-CTLA-4 (tumor cell CTLA-4) and I-CTLA-4 (interstitial lymphocyte CTLA-4) was 48.8% and 44.0%, respectively. The number of enrolled patients with a higher PLR level (≥119) was 48. The prognostic value of T-CTLA-4, I-CTLA-4, and PLR in ESCC patients was not detected. However, patients with both a low T-CTLA-4 expression level and a low PLR level that had longer OS (p = 0.023) were found. The prognostic role of T-CTLA-4(-) +PLR (-) status in ESCC patients was also confirmed in multivariate analyses (p = 0.027). CONCLUSION: These results demonstrated the potential prognostic value of combined analysis of CTLA-4 and PLR in ESCC patients.	esophagus
The impact of the nodal status on the overall survival of non-surgical patients with esophageal squamous cell carcinoma.	BACKGROUND: The prognosis of N categories for patients with non-surgical esophageal carcinoma based on the number of metastatic lymph nodes is controversial. The present study analyzes prognostic implications of the number, extent, and size of metastatic lymph nodes for patients with esophageal squamous cell carcinoma (ESCC) treated with definitive (chemo-)radiotherapy to provide more information on treatment strategy. METHODS: We reviewed 357 ESCC patients treated with definitive radiotherapy between January 2013 and March 2016 retrospectively. We assessed potential associations between the involved extent (N0, 1 region, 2 regions, and 3 regions), number (N0, 1-2, 3-6, and ≥ 7), and size (N0, ≤2 cm, and > 2 cm) of metastatic lymph nodes and overall survival. Multivariate analyses of the clinicopathological factors were performed using the Cox proportional hazard model. RESULTS: 5-year survival rates were 43.6% for patients in the N0 group and 29.3% in the N+ group (p = 0.001). Kaplan-Meier analyses for all cases revealed that there were significant differences in survival based on the extent (the OS rates at 3 years were 53.3% for patients in the N0 group, 45.7% in the 1 region-involved group, 28.0% in the 2 regions-involved group, and 13.3% in the 3 regions-involved group, P < 0.001), number (the OS rates at 3 years were 49.0% for patients in the 1-2 LNs group, 27.8% in the 3-6 LNs group, 0 in the ≥7LNs group, P < 0.001), and size (the OS rates at 3 years were 41.6% for patients in the LNs ≤2 cm group and 20.7% in the LNs > 2 cm group, P = 0.001) of metastatic LNs. One hundred seventy-two patients (48.2%) had experienced GTV failure, 157 (43.1%) had distant failure, 49 (13.7%) had out-of-GTV nodal failure, and 70 patients (19.6%) had no evidence of disease at the last follow-up. Nodal status correlated statistically with GTV failure. Patients with LN metastases in the abdominal region had worse survival rates than those with metastases in the other regions. The extent and number of metastatic LNs, T category, Primary tumor location, and chemotherapy were independent prognostic factors of OS in multivariate analyses. CONCLUSIONS: For patients with ESCC who received definitive (chemo-)radiotherapy, the number, extent, and size of metastatic LNs were prognostic factors, particularly of the T2/3 disease. Patients with LN metastases in the abdominal region had worse survival.	esophagus
Aspirin as an adjuvant treatment for cancer: feasibility results from the Add-Aspirin randomised trial.	BACKGROUND: Preclinical, epidemiological, and randomised data indicate that aspirin might prevent tumour development and metastasis, leading to reduced cancer mortality, particularly for gastro-oesophageal and colorectal cancer. Randomised trials evaluating aspirin use after primary radical therapy are ongoing. We present the pre-planned feasibility analysis of the run-in phase of the Add-Aspirin trial to address concerns about toxicity, particularly bleeding after radical treatment for gastro-oesophageal cancer. METHODS: The Add-Aspirin protocol includes four phase 3 randomised controlled trials evaluating the effect of daily aspirin on recurrence and survival after radical cancer therapy in four tumour cohorts: gastro-oesophageal, colorectal, breast, and prostate cancer. An open-label run-in phase (aspirin 100 mg daily for 8 weeks) precedes double-blind randomisation (for participants aged under 75 years, aspirin 300 mg, aspirin 100 mg, or matched placebo in a 1:1:1 ratio; for patients aged 75 years or older, aspirin 100 mg or matched placebo in a 2:1 ratio). A preplanned analysis of feasibility, including recruitment rate, adherence, and toxicity was performed. The trial is registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN74358648) and remains open to recruitment. FINDINGS: After 2 years of recruitment (October, 2015, to October, 2017), 3494 participants were registered (115 in the gastro-oesophageal cancer cohort, 950 in the colorectal cancer cohort, 1675 in the breast cancer cohort, and 754 in the prostate cancer cohort); 2719 (85%) of 3194 participants who had finished the run-in period proceeded to randomisation, with rates consistent across tumour cohorts. End of run-in data were available for 2253 patients; 2148 (95%) of the participants took six or seven tablets per week. 11 (0·5%) of the 2253 participants reported grade 3 toxicity during the run-in period, with no upper gastrointestinal bleeding (any grade) in the gastro-oesophageal cancer cohort. The most frequent grade 1-2 toxicity overall was dyspepsia (246 [11%] of 2253 participants). INTERPRETATION: Aspirin is well-tolerated after radical cancer therapy. Toxicity has been low and there is no evidence of a difference in adherence, acceptance of randomisation, or toxicity between the different cancer cohorts. Trial recruitment continues to determine whether aspirin could offer a potential low cost and well tolerated therapy to improve cancer outcomes. FUNDING: Cancer Research UK, The National Institute for Health Research Health Technology Assessment Programme, The MRC Clinical Trials Unit at UCL.	esophagus
[Expert recommendation for robot-assisted esophagectomy (2019 edition)].	Minimally invasive esophagectomy for the surgical treatment of esophageal cancer has gradually been recognized and applied. With the application of robot-assisted technology in esophageal surgery, robot-assisted esophagectomy has been carried out in large domestic centers, and its feasibility and safety have been recognized by some domestic experts. In view of no advice or guidelines about robot-assisted esophagectomy has been written before, Committee of Esophageal Cancer in China Anticancer Association organized relevant domestic experts to establish this expert recommendation for standardization of robot-assisted esophagectomy, aiming at helping surgeons perform this complex procedure safely.	esophagus
Current status of radiotherapy for patients with thoracic esophageal cancer in Japan, based on the Comprehensive Registry of Esophageal Cancer in Japan from 2009 to 2011 by the Japan Esophageal Society.	BACKGROUND: Although esophagectomy is the standard treatment for resectable esophageal cancer, chemoradiotherapy or radiotherapy alone is also selected for some cases. However, there have been very few detailed studies conducted on a large scale on the efficacy of these treatments in Japan. METHODS: Of the patients enrolled in the Comprehensive Registry of Esophageal Cancer in Japan by the Japan Esophageal Society for the 2015-2017 surveys (patients treated between 2009 and 2011), the data of 388 patients treated by definitive radiotherapy alone (RTx) and 1964 patients treated by definitive chemoradiotherapy (CRTx) were analyzed. RESULTS: The median age of the patients was 78 years in the RTx group and 69 years in the CRTx group; thus, the proportion of elderly patients was significantly higher in the RTx group than in the CRTx group (p < 0.0001). With regard to the rates of treatment by the two modalities according to the depth of invasion, extent of lymph node metastasis, and disease stage, the treatment rate by CRTx increased more significantly than that by RTx as the disease progressed (p < 0.0001). With regard to the distribution of the total irradiation dose, 11.4% and 2.3% of patients in the RTx and CRTx groups, respectively, received a dose of 67 Gy or more; thus, the RTx group received significantly higher total irradiation doses (p < 0.0001). In the RTx group, the 5-year overall survival rate was 23.2%, and the rates in patients with cStage 0-I, II, III, and IV disease were 41.8%,18.5%, 9.3%, and 13.9%, respectively. In the patients of the RTx group showing complete response (CR), the 5-year overall survival rate was 46.6% and the rates in patients with cStage 0-I, II, III, and IV disease were 54.8%, 39.6%, 32.4%, and 38.9%, respectively. In the CRTx group, the 5-year overall survival rate was 30.6% and the rates in patients with cStage 0-I, II, III, and IV disease were 57.8%, 47.8%, 23.4%, and 13.0%, respectively. In the patients of the CRTx group showing CR, the 5-year overall survival rate was 59.2% and the rates in patients with cStage 0-I, II, III, and IV disease were 67.9%, 59.5%, 56.5%, and 39.6%, respectively. CONCLUSION: This study revealed the current status of treatment of esophageal cancer in Japan, and we think that we have been able to establish the grounds for explaining to patients with esophageal cancer and their families the treatment decisions made for them in daily clinical practice.	esophagus