crossing96/oncoscreening huggingface dataset:
Molecular Dynamics in Esophageal Adenocarcinoma: Who's in Control?	Esophageal adenocarcinoma (EAC) is one of the fastest-growing cancers in the world. It occurs primarily due to the chronic gastroesophageal reflux disease (GERD), during which the esophageal epithelium is frequently exposed to the acidic fluid coming up from the stomach. This triggers gene mutations in the esophageal cells, which may lead to EAC development. While p53 is activated to get rid of the mutated cells, NFκB orchestrates the remaining cells to heal the wound. However, if the mutations happen to TP53 (a common occasion), the mutant product turns to support tumorigenesis. In this case, NFκB goes along with the mutant p53 to facilitate cancer progression. TRAIL is one of the cytokines produced in response to GERD episodes and it can kill cancer cells selectively, but its clinical use has not been as successful as expected, because some highly sophisticated defense mechanisms against TRAIL have developed during the malignancy. To clear the obstacles for TRAIL action, using a second agent to disarm the cancer cells is required. CCN1 appears to be such a molecule. While supporting normal esophageal cell growth, CCN1 suppresses malignant transformation by inhibiting NFκB and kills the EAC cell through TRAIL-mediated apoptosis.	esophagus
Wide Gastric Conduit Increases the Risk of Benign Anastomotic Stricture After Esophagectomy.	BACKGROUND: To identify the association between the width of the gastric conduit and the benign anastomotic stricture (BAS) after esophagectomy with end-to-side cervical anastomosis for esophageal cancer. METHODS: Patients with esophageal cancer who underwent esophagectomy between July 2013 and July 2014 were included in this study. The gastric conduit was used for reconstruction in all patients and end-to-side cervical anastomosis were performed using a circular stapler. The patients were divided into a narrow group (3-5 cm) and a wide group (>5 cm) based on the gastric conduit width. Univariate and multivariate logistic regressions were used to analyze the possible factors (patients' age, gender, preoperative comorbidities, neoadjuvant chemotherapy, gastric conduit width, anastomotic leakage) that could affect the incidence of BAS. RESULTS: Two-hundred and one patients were included in this study. The median follow-up period was 29 months (17-58 months). Seven cases (3.5%) showed anastomotic leakage in the postoperative period and 38 patients (18.9%) developed BAS; all within the first year of follow-up. In univariate analysis, the width of the gastric conduit was the only risk factor for the development of BAS (odds ratio [OR] = 3.36, P = .005). In multivariate logistic regression analysis, the wide group was an independent significant risk factor for the development of BAS developing compared with the narrow group (OR = 2.84, P = .02). CONCLUSIONS: A wide gastric conduit width (>5 cm) is an independent risk factor for the development of BAS after esophagectomy and stapled cervical end-to-side anastomosis for esophageal cancer.	esophagus
Patterns of Use of Induction Therapy for T2N0 Esophageal Cancer.	BACKGROUND: Induction therapy for patients with cT2N0M0 esophageal cancer is controversial. We performed a retrospective cohort analysis of the National Cancer Database to examine the patterns of use of induction therapy for this population. METHODS: The National Cancer Database was queried for patients with cT2N0M0 esophageal cancer who underwent esophagectomy (2004-2015). Patients were stratified by upfront surgery or induction therapy. Overall survival was analyzed and a multivariable logistic regression performed to identify factors associated with receipt of induction therapy. RESULTS: Overall 2540 patients met study criteria: 1177 (46%) received upfront esophagectomy and 1363 (53%) received induction therapy. Patients receiving induction therapy were more likely to be younger, male, without comorbidities, privately insured, and treated at a nonacademic center. These patients were also less likely to be treated in highest volume surgery centers. In multivariable regression, factors independently associated with receipt of induction therapy included later year of diagnosis, increasing tumor size, and increasing tumor grade. Factors associated with upfront esophagectomy included advancing age, comorbidities, lack of insurance, geographic location, and highest volume centers. The receipt of induction chemotherapy was not associated with a survival benefit compared with no induction therapy. CONCLUSIONS: Several patient-, treatment center-, and tumor-related factors are associated with receipt of induction therapy for cT2N0M0 esophageal cancer, although induction therapy is not associated with a survival benefit. Further inquiry into these differences and the potential benefit or lack thereof of induction therapy should be conducted to provide more equitable and appropriate care for patients with esophageal cancer.	esophagus
Peripheral blood cell count ratios are predictive biomarkers of clinical response and prognosis for non-surgical esophageal squamous cell carcinoma patients treated with radiotherapy.	BACKGROUND: Peripheral blood cell count ratios, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), have been reported to be prognostic factors in many malignancies as markers of inflammation and immune status. The aim of this study was to determine whether NLR, PLR, or LMR can be clinical response and prognostic biomarkers of non-surgical esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy. METHODS: 193 non-surgical ESCC patients who underwent radiotherapy were retrospectively analyzed. The peripheral blood cell count ratios were obtained before, during (weekly) and at the end of the treatment. Then, we compared the subsequent results with the corresponding pretreatment values and computed the rates of change, which were defined as cNLR, cPLR, and cLMR. Univariate and multivariate Cox regression analyses were used for overall survival (OS). Ordinal logistic regression was used to analyze the clinical response. RESULTS: In multivariate analysis, cNLR at week 4(P = .026) and week 5(P = .025) during radiotherapy were significantly associated with OS, along with BMI, tumor stage, tumor length, tumor location, and grade of adverse events. Besides, BMI, tumor stage, tumor length, adverse event grade, cNLR at week 4(P = .044) and week 5(P = .013), and cPLR at week 4(P = .034) and week 5(P = .015) were significantly associated with the clinical response in the multivariate logistic regression analysis. CONCLUSIONS: The cNLR at weeks 4 and 5 was negatively correlated with the OS and clinical response of non-surgical ESCC patients treated with radiotherapy. The elevated cPLR at weeks 4 and 5 was only related to poor clinical response.	esophagus
Potential therapeutic effect of targeting glycogen synthase kinase 3β in esophageal squamous cell carcinoma.	Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal cancer and is often refractory to current therapies. Development of efficient therapeutic strategies against ESCC presents a major challenge. Glycogen synthase kinase (GSK)3β has emerged as a multipotent therapeutic target in various diseases including cancer. Here we investigated the biology and pathological role of GSK3β in ESCC and explored the therapeutic effects of its inhibition. The expression of GSK3β and tyrosine (Y)216 phosphorylation-dependent activity was higher in human ESCC cell lines and primary tumors than untransformed esophageal squamous TYNEK-3 cells from an ESCC patient and tumor-adjacent normal esophageal mucosa. GSK3β-specific inhibitors and small interfering (si)RNA-mediated knockdown of GSK3β attenuated tumor cell survival and proliferation, while inducing apoptosis in ESCC cells and their xenograft tumors in mice. GSK3β inhibition spared TYNEK-3 cells and the vital organs of mice. The therapeutic effect of GSK3β inhibition in tumor cells was associated with G0/G1- and G2/M-phase cell cycle arrest, decreased expression of cyclin D1 and cyclin-dependent kinase (CDK)4 and increased expression of cyclin B1. These results suggest the tumor-promoting role of GSK3β is via cyclin D1/CDK4-mediated cell cycle progression. Consequently, our study provides a biological rationale for GSK3β as a potential therapeutic target in ESCC.	esophagus
Comparison of outcomes of pedicled jejunal and colonic conduit for esophageal reconstruction.	BACKGROUND: At present, the gastric tube is the first choice for esophageal reconstruction after esophagectomy for various benign and malignant diseases. However, when the stomach is not available, a pedicled jejunum or colon is used to reconstruct the esophagus. The present study aimed to compare the postoperative outcomes and quality of life of patients receiving jejunal and colonic conduits. METHODS: In the present retrospective study, the clinical data of 71 patients with esophageal carcinoma, who received jejunal reconstruction (jejunum group, n = 34) and colonic reconstruction (colon group, n = 37) from 2005 to 2015, were compared. RESULTS: Compared with the colon group, the jejunum group had a lower incidence of postoperative anastomotic leakage, lesser duration of postoperative drainage, and faster recovery. Furthermore, the scores were better in the jejunum group than in the colon group, in terms of short-term overall quality of life, physical function and social relationships. Moreover, the jejunal group had a significantly lower frequency of pH < 4 simultaneous reflux time > 5 min (N45) and the longest reflux time (LT) at 24 weeks after surgery. CONCLUSION: In esophageal cancer, when gastric tube construction is not feasible, a pedicled jejunum may be preferred over a colonic conduit due to lower incidence of acid reflux, anastomotic leakage and higher postoperative short-term quality of life, and rapid postoperative recovery.	esophagus
Reduced LINC00551 expression promotes proliferation and invasion of esophageal squamous cancer by increase in HSP27 phosphorylation.	Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers, and long noncoding RNAs (lncRNAs) regulate gene expression or activities. This study investigated the role of lncRNA LINC00551 in ESCC development and progression. Three paired ESCC and normal tissues were subjected to next-generation sequencing and we identified 82 upregulated and 60 downregulated lncRNAs, including LINC00551, which was confirmed to markedly downregulated in 78 ESCC tissues and in the Gene Expression Profiling Interactive Analysis data set. Downregulated LINC00551 expression was associated with lymph node metastasis, advanced TNM stage, and tumor size. Moreover, downregulated LINC00551 expression was also associated with poor progression-free survival and overall survival of ESCC patients. In vitro and in vivo, LINC00551 overexpression inhibited ESCC cell proliferation and invasion, whereas knockdown of LINC00551 expression promoted ESCC cell proliferation and invasion. RNA pull-down and mass spectrometry assays identified the potential LINC00551 binding proteins, and HSP27 was a promising LINC00551 targeting proteins after RNA immunoprecipitation assay. At the protein level, LINC00551 bound to and decreased HSP27 phosphorylation, and in turn, downregulated ESCC cell proliferation and invasion. The current study demonstrated the functional significance of LINC00551 in ESCC development, progression, and prognosis. Further study will assess LINC00551 as a novel prognostic marker or therapeutic target for ESCC.	esophagus
Characterization of the Esophageal Microbiota and Prediction of the Metabolic Pathways Involved in Esophageal Cancer.	Esophageal microbiota plays important roles in esophageal cancer. Esophagectomy, as the most important therapeutic way, contributes to changes of esophageal microbiome. However, there are few studies examining the esophageal microbiome and the metabolic changes before and after esophagectomy. The present study characterized the esophageal microbiome of 17 patients with esophageal squamous cell carcinoma (ESCC), 11 patients with esophagogastric junction (EGJ) cancer, 15 patients at 9-12 months after radical esophagectomy and 16 healthy controls (HC). 16S ribosomal RNA gene sequencing was used to evaluate the microbiome and predict the metabolic pathways. Our results showed that the microbial diversity was significantly lower in ESCC, EGJ and post-ESCC groups than that in the HC group. The abundance of Fusobacteria was higher (7.01 vs. 1.12%, P = 0.039) and the abundance of Actinobacteria (1.61 vs. 4.04%) was lower in the ESCC group than that in the HC group. We found significant differences in the abundance of Bacteroidetes (20.45 vs. 9.86%, P = 0.026), Fusobacteria (7.01 vs. 1.66%, P = 0.030) between ESCC and post-ESCC groups. The results of microbial composition analysis and PICRUSt demonstrated significant differences between ESCC and HC groups. The β diversity and PICRUSt suggested that the microbial composition and metabolic pathways were similar to HC group after esophagectomy. The monitoring of the esophagus microbiota may be an essential method to predict the recurrence of tumor.	esophagus
Endoscopic Submucosal Dissection Versus Surgery for Superficial Esophageal Squamous Cell Carcinoma: A Propensity Score-Matched Survival Analysis.	INTRODUCTION: Endoscopic submucosal dissection (ESD) is a preferred treatment option for superficial esophageal squamous cell carcinoma (SESCC). However, only few studies compared long-term survival outcomes of ESD with surgery. This study compared the overall survival (OS), recurrence-free survival, and complication rates of ESD with those of surgery. METHODS: We reviewed patients who underwent ESD (n = 70) or surgery (n = 114) for SESCC at Seoul National University Hospital from 2011 to 2017. A propensity score-matched analysis was used to reduce selection bias. To increase the precision of our results interpretation, subgroups were analyzed according to the depth of tumor invasion. RESULTS: In the matching study, the ESD group (n = 34) showed comparable survival outcomes with the surgery group (n = 34). The 5-year OS rates were 89.4% vs 87.8% for the ESD and the surgery groups, respectively; similarly, the 5-year recurrence-free survival rates were 90.9% and 91.6%, respectively. The ESD group showed a lower early major complication rate (2.9% [1 of 34] vs 23.5% [8 of 34], P < 0.001) and shorter hospital stay (median, 3.0 days vs 16.5 days, P < 0.001) than the surgery group. In the tumor in situ (Tis)-subgroup, ESD showed better OS than esophagectomy (P = 0.030). Between-group comparisons of survival outcomes in the T1a and T1b subgroups revealed no significant differences. DISCUSSION: Long-term outcomes of ESD are comparable with surgery for patients with SESCC. For early major complications and duration of hospital stay, ESD was associated with better outcomes than radical surgery. These results support ESD as the preferred treatment option for SESCC.	esophagus
Identification of KHSRP-Regulated RNAs in Esophageal Cancer by Integrated Bioinformatics Analysis.	Background: The objective of this study was to identify key molecules that included long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs involved in esophageal cancer with KH-type splicing regulatory protein (KHSRP) knockdown. Materials and Methods: GSE99422 and GSE99423 from Gene Expression Omnibus database were extracted. After differentially expressed analysis of miRNAs, lncRNAs, and mRNAs, the lncRNAs-mRNAs interaction was obtained. Then the protein-protein interaction (PPI) network and module analyses were performed for differentially expressed mRNAs (DEmRNAs). Combined with miRWalk tool and DIANA-LncBase tool, regulating relationship between differentially expressed miRNAs (DEmiRNAs) and DEmRNAs/DElncRNAs were predicted. Finally, mRNA-miRNA-lncRNA regulatory network construction was established by Cytoscape software. Finally, the key genes were validated based on the Gene Expression Profiling Interactive Analysis (GEPIA) database. Results: Totally, 2,027 DEmiRNAs, 3,480 DElncRNAs, and 18,293 DEmRNAs were screened. The PPI network included 399 nodes and 1671 interaction pairs, and two function models (Cluster 1 and Cluster 2) were separately identified. The PLK1 was a hub in the Cluster 1, which mainly enriched in the function of nuclear division. Then the competing endogenous RNA (ceRNA) network was constructed with 20 miRNAs, 66 lncRNA, and 202 mRNA. Here, lncRNA RP11-159D12.2 might function as a ceRNA in regulating BIRC5 expression of esophagus cancer through competitively binding to hsa-miR-4430. BIRC5 was mainly enriched in the function of mitotic nuclear division. Besides, the expression of BIRC5 and PLK1 genes was upregulated in tumor tissues compared with normal controls. Also, the correlation analysis showed that the key genes (BIRC5 and PLK1) were validated to be positively correlated with KHSRP. Conclusions: PLK1, BIRC5, hsa-miR-4430, and lncRNA RP11-159D12.2 were likely to be associated with esophageal cancer development.	esophagus
Lymph node dissection and recurrent laryngeal nerve protection in minimally invasive esophagectomy.	Until now, neoadjuvant therapy plus surgical resection of the primary tumor and potential metastatic lymph nodes (LNs) has been the current optimal treatment for locally advanced thoracic esophageal cancer (EC). LN metastasis is one of the most negative prognostic factors for thoracic esophageal squamous cell carcinoma (ESCC). However, the extent of LN dissection for thoracic ESCC has long been controversial worldwide. LNs along the recurrent laryngeal nerve (RLN) were reported to have the highest frequency of metastases in thoracic ESCC, so lymphadenectomy along the bilateral RLN is necessary but quite challenging because of a high frequency of recurrent nerve palsy and related postoperative complications. With the development of minimally invasive devices and techniques in recent years, minimally invasive esophagectomy (MIE) has been widely applied in EC surgery. The topics of what the optimal extent of lymphadenectomy is and how the recurrent nerve should be well protected during MIE have been debated in recent years. The purpose of our review is specifically to address the patterns of LN metastasis, the extent of LN dissection, and the protection of the RLN in MIE for thoracic ESCC.	esophagus
OP16 induces deadly autophagy and apoptosis of cells by inhibiting Akt in esophageal squamous cell carcinoma.	BACKGROUND: OP16, a derivative of the novel ent-kaurene diterpenoid compound separated from Rabdosia rubescens, has been confirmed for its efficacy and safety in the treatment of esophageal squamous cell carcinoma (ESCC) in our previous study. However, the precise mechanisms of tumor lethality mediated by OP16 have not yet been fully characterized. AIMS: To investigate the effects and molecular mechanism of OP16 on autophagy and apoptosis of ESCC cells. METHODS: Effects and mechanism of OP16 on autophagy of ESCC cells were first detected by Western blot, immunofluorescence, mRFP-GFP-LC3 adenovirus infection and transmission electron microscope. Next, function of autophagy and apoptosis induced by OP16 on cell death was investigated by flow cytometry and CCK-8 assay. Finally, molecular mechanism of OP16 affecting autophagy and apoptosis of ESCC cells was explored by Western blot. RESULTS: We demonstrated that OP16 could induce autophagy by promoting the formation of autophagosome and autolysosome, and promote autophagic cell death in ESCC. Furthermore, we also found that OP16 could promote cell apoptosis by activating mitochondria apoptosis pathway in ESCC. Finally, we demonstrated that OP16 affecting autophagy and mitochondria apoptosis pathway was mediated by phosphorylation of Akt. CONCLUSION: Our data show that OP16 could promote cell death through affecting autophagy and mitochondria apoptosis pathway mediated by Akt in ESCC, which enriches the theoretical mechanism of anti-tumor effects of OP16 and provides a basis for treatment of OP16 on ESCC.	esophagus
Characteristics and short-term outcomes of patients with esophageal cancer with unplanned intensive care unit admissions: a retrospective cohort study.	OBJECTIVE: To depict the clinical presentation and outcomes of a cohort of critically ill patients with esophageal cancer. METHODS: We carried out a multicenter retrospective study that included patients with esophageal cancer admitted to intensive care units with acute illness between September 2009 and December 2017. We collected the demographic and clinical characteristics of all included patients, as well as organ-support measures and hospital outcomes. We performed logistic regression analysis to identify independent factors associated with in-hospital mortality. RESULTS: Of 226 patients included in the study, 131 (58.0%) patients died before hospital discharge. Squamous cell carcinoma was more frequent than adenocarcinoma, and 124 (54.9%) patients had metastatic cancer. The main reasons for admission were sepsis/septic shock and acute respiratory failure. Mechanical ventilation (OR = 6.18; 95%CI 2.86 - 13.35) and metastatic disease (OR = 7.10; 95%CI 3.35 - 15.05) were independently associated with in-hospital mortality. CONCLUSION: In this cohort of patients with esophageal cancer admitted to intensive care units with acute illness, the in-hospital mortality rate was very high. The requirement for invasive mechanical ventilation and metastatic disease were independent prognostic factors and should be considered in discussions about the short-term outcomes of these patients.	esophagus
Altered expression of TGF-β1 and TGF-βR2 in tissue samples compared to blood is associated with food habits and survival in esophageal squamous cell carcinoma.	In the transforming growth factor β (TGF-β) signaling pathway, TGF-β1 and TGF-β receptor 2 (TGF-βR2) are essential regulatory components which play an important role in different type of cancer. Expressions of TGF-β1 and TGF-βR2 were done by real-time qPCR in both biopsy and blood samples collected from esophageal squamous cell carcinoma (ESCC) patients (n = 76). The expression profiles were correlated with different lifestyle factors and clinicopathological parameters. Kaplan-Meier survival analysis and Cox regression analysis were performed to estimate survival and hazard outcomes of different parameters. TGF-β1 showed upregulation in 91% tissue samples (2.84 ± 1.34*) and 55% blood samples (2.43 ± 1.24*) whereas expression of TGF-βR2 showed downregulation in 89% tissue samples (0.27 ± 0.23*) and 75% blood samples (0.30 ± 0.26*). Among all the parameters, TGF-β1 expression is significant with histopathology grade, consumption of betel nut and smoked food whereas TGF-βR2 expression is significant only with dysphagia grade in both blood and tissue samples and while analyzing both male and female patients separately. Consuming alcohol and hot food, difference in tumor stage and metastasis were found to have statistically significant (P < 0.05) impact on survival and mortality of male patients while consuming hot food, tobacco, metastasis and TGF-βR2 expression in tissue level were found to associate with survival and mortality of female patients. Expression of both TGF-β1 and TGF-βR2 in tissue samples may be prospective biomarkers for screening of ESCC among the Northeast population. Survival outcomes and hazard analysis supports the importance of some clinicopathological and lifestyle factors on ESCC development, whereas expression study depicts association of change in expression of the studied genes in ESCC patients. *Mean fold change.	esophagus