crossing96/oncoscreening huggingface dataset:
MDM2 and its functional polymorphism SNP309 contribute to the development of esophageal carcinoma.	BACKGROUND: Overexpression of the murine double minute 2 (MDM2) has been explored in many tumors with high proliferation and anti-apoptosis ability. However, the role of MDM2 and its functional single nucleotide polymorphism (SNP) rs2279744 (also known as SNP309) in esophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: We performed a genotype study of blood samples in 360 ESCC patients and 360 healthy control individuals to determine the risk of various rs2279744 in ESCC. To further evaluate the role of rs2279744 in regulating MDM2 expression, we performed an allele-specific reporter assay and investigated whether the SNP-containing sequences functioned as an active enhancer. To examine the functional role of MDM2 on esophageal cancer cell lines, we carried out an MTS assay and flow cytometry analysis. RESULTS: From the genotyping study, we found that GG genotype of SNP309 significantly increased the risk of ESCC in an additive model [odds ratio (OR) = 2.55, 95% confidence interval (CI) = 1.66-3.89, p = 1.50 × 10(-5) ) and in a recessive model (OR = 2.44, 95% CI = 1.69-3.51, p = 1.60 × 10(-8) ). Furthermore, the G allele was significantly associated with a higher risk of ESCC (OR = 1.56, 95% CI = 1.26-1.92, p = 2.81 × 10(-5) ). In multivariate logistic regression analysis, the GG genotype had increased the occurrence of ESCC by 2.39-fold (95% CI = 1.48-3.8). Compared to the T allele, the variant G allele had significantly higher luciferase activity on the promoter of MDM2 in both cell lines. By transfecting the gene to ESCC lines, we showed that overexpression of MDM2 significantly promote cell proliferation and anti-apoptosis. CONCLUSIONS: The MDM2 promoter SNP309 is a risk factor for esophageal cancer. MDM2 promotes the proliferation and anti-apoptosis of ESCC.	esophagus
[Barrett-Screening: Rational, current concepts and perspectives].	"Though showing an increasing incidence over the past 20 years, esophageal adenocarcinoma (EAC) remains a rather uncommon cancer (i. e., compared to colorectal and gastric cancer). Once detected, the prognosis of this cancer entity is still very poor. Hence, in spite of some unfavorable prerequisites to systematic screening, the development of a screening concept for Barrett's esophagus (BE) and EAC seems worthwhile. Nowadays, screening for BE and EAC is based on conventional endoscopy, mostly conducted individually in patients with reflux complaints (gastroesophageal reflux disease-GERD). Biopsies are taken obligatorily and are the centerpiece of diagnosis and scheduling of surveillance. So far, endoscopy is the diagnostic gold standard, but it is expensive and obviously lacks effectiveness-8 of 10 cases of EAC are not detected in endoscopic screening (and surveillance) but by an opportunistic first-time endoscopy. Therefore, new methods for BE/EAC screening are strongly desirable. Research must be concentrated to favor procedures applicable for a screening of the population in a primary care setting. For that, the first step needs to consist of identifying a subgroup of people ""at risk"", which in a second step can be risk assessed and followed up by endoscopy and biopsy. From all screening variants, which have been actually tested in clinical application and experimental research, biomarker-based techniques seem to be most promising. Among those-under the aspect of costs and practicability-the Cytosponge, in addition with a panel of biomarkers, seemed to be promising in clinical trials."	esophagus
A rare invasion route for differentiated thyroid carcinoma: The tracheoesophageal common party wall.	Thyroid carcinoma can infiltrate the aerodigestive tract. Invasion via the common party wall of the tracheoesophageal groove (TEG) is rare. A review of patients with thyroid cancer invading the aerodigestive tract was performed. We describe three cases of invasive thyroid cancer presenting 4 to 6 years after the initial thyroidectomy. Original pathology showed positive margins near the recurrent laryngeal nerve and TEG. A partial tracheal resection with a stair-step reconstruction was performed in one case; the other cases required total laryngopharyngectomy. Surgeons should be prepared to perform oncologically complete resections at the primary surgery to avoid potentially significant clinical consequences requiring aggressive surgery. Laryngoscope, 129:E455-E459, 2019.	esophagus
Repression of AXL expression by AP-1/JNK blockage overcomes resistance to PI3Ka therapy.	AXL overexpression is a common resistance mechanism to anti-cancer therapies, including the resistance to BYL719 (Alpelisib) - the p110α isoform specific inhibitor of phosphoinositide 3-kinase (PI3K) - in esophagus and head and neck squamous cell carcinoma (ESCC, HNSCC respectively). However, the mechanisms underlying AXL overexpression in resistance to BYL719 remain elusive. Here we demonstrated that the AP-1 transcription factors, c-JUN and c-FOS, regulate AXL overexpression in HNSCC and ESCC. The expression of AXL was correlated with that of c-JUN both in HNSCC patients and in HNSCC and ESCC cell lines. Silencing of c-JUN and c-FOS expression in tumor cells downregulated AXL expression and enhanced the sensitivity of human papilloma virus positive (HPVPos) and negative (HPVNeg) tumor cells to BYL719 in vitro. Blocking of the c-JUN N-terminal kinase (JNK) using SP600125 in combination with BYL719 showed a synergistic anti-proliferative effect in vitro, which was accompanied by AXL downregulation and potent inhibition of the mTOR pathway. In vivo, the BYL719-SP600125 drug combination led to the arrest of tumor growth in cell line-derived and patient-derived xenograft models, and in syngeneic head and neck murine cancer models. Collectively, our data suggests that JNK inhibition in combination with anti-PI3K therapy is a new therapeutic strategy that should be tested in HPVPos and HPVNeg HNSCC and ESCC patients.	esophagus
Malignant melanoma of the esophagus complicated with poorly differentiated mucinous adenocarcinoma of the stomach: A case report.	RATIONALE: Primary malignant melanoma of the esophagus (PMME) is a rare malignancy that only accounts for <2% of all primary esophageal tumors. Here, we report the even rarer occurrence of PMME in combination with poorly differentiated mucinous adenocarcinoma of the stomach. PATIENT CONCERNS: A 64-year-old man was presented to the hospital with >1 month of eating dysphagia. Enhanced computed tomography (CT) scan only found a space-occupying lesion in the lower esophagus with moderate enhancement. However, gastroscope showed not only esophageal masses, but also gastric mucosa changes. DIAGNOSES: Poorly differentiated mucinous adenocarcinoma and PMME were diagnosed based on pathological biopsy and immunohistochemical methods. INTERVENTIONS: The patient underwent laparoscopic gastric cancer radical surgery, esophageal resection, and colonic replacement of the esophagus. OUTCOMES: Abdominal CT and esophagography performed 1 week after surgery showed that it was consistent with postoperative changes without other abnormalities. However, the patient died 3 months after discharge without receiving any other treatment. LESSONS: This case suggests more attention should be drawn to the diagnosis of multiple primary malignant neoplasms in elder patients, and also highlights the need to fulfill comprehensive examinations before surgery in case of misdiagnosis. Besides, it is challenging to finding a reasonable treatment for such rare condition.	esophagus
Preoperative esophageal stenting and short-term outcomes of surgery for esophageal cancer in a population-based study from Finland and Sweden.	Population-based studies examining whether preoperative esophageal stenting influences the short-term outcomes after esophagectomy for esophageal cancer are lacking. This nationwide cohort combining data from Finland and Sweden was conducted to cover this gap. Patients with locally advanced esophageal cancer (T ≥ 3 and/or N ≥ 1, M0) who underwent esophagectomy between 2007 and 2014 were identified from nationwide registries in Finland and Sweden. The study exposure was preoperative stenting. The primary outcomes were 30- and 90-day mortality. Secondary outcomes were length of hospital stay and 30- and 90-day readmission rates. Multivariable Cox and linear regression analyses provided hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex, comorbidity, tumor histology, year of surgery, and country. Of all 1029 participating patients who underwent surgery for locally advanced esophageal cancer, 127 (12.3%) had an esophageal stent inserted preoperatively. The absolute 30-day mortality rates were higher in stented patients (3.9%) than in those without a stent (1.6%), but the HR was not statistically significantly increased (HR 2.42; 95% CI 0.85-6.92). Similarly, the absolute 90-day mortality rates were increased after preoperative stenting (11.8%) compared to no stenting (7.0%), but again the HR was not statistically significantly increased (HR 1.68; 95% CI 0.95-2.98). Preoperative stenting did not influence length of hospital stay or readmission rates. The possibly increased short-term mortality after preoperative stenting in patients who undergo esophagectomy for esophageal cancer indicated in this study suggests a cautious approach to preoperative stenting until future research or meta-analyses provide a more definite answer.	esophagus
Polymorphism rs2395655 affects LEDGF/p75 binding activity and p21WAF1/CIP1 gene expression in esophageal squamous cell carcinoma.	p21WAF1/CIP1 (p21) plays critical roles in cell-cycle regulation and DNA repair and is transcriptionally regulated through p53-dependent or -independent pathways. Bioinformatic analysis predicated one stress-response element (STRE) implicated in single nucleotide polymorphism (SNP) rs2395655 of the p21 promoter. Here, we investigated the transcriptional regulatory function of rs2395655 variant genotype and analyzed its associations with the p21 expression and clinical outcomes in esophageal squamous cell carcinoma (ESCC) patients. Luciferase assay results showed significantly increased transcriptional activity of the rs2395655 G allele-containing p21 promoter compared with rs2395655 A allele-containing counterpart, especially in ESCC cells with ectopic LEDGF/p75 expression. Furthermore electrophoretic mobility shift assay using the rs2395655 G or A allele-containing probe and chromatin immunoprecipitation assay with specific anti-LEDGF/p75 antibody indicated the potential binding activity of LEDGF/p75 with the STRE element implicated in rs2395655 G allele of the p21 promoter. Subsequent specific RNA interference-mediated depletion or ectopic expression of LEDGF/p75 caused obviously down- or up-regulated expression of p21 mRNA in ESCC cells harboring rs2395655 GG genotype but not cells with rs2395655 AA genotype. Furthermore, rs2395655 GG genotype carriers showed significantly elevated p21 protein expression and conferred survival advantage in both univariate and multivariate analyses in total 218 ESCC patients. Our findings suggest that LEDGF/p75 regulates the p21 expression in ESCC cells through interacting with STRE element implicated in polymorphism rs2395655 and the elevated p21 protein expression and rs2395655 GG genotype may serve as positive prognostic factors for ESCC patients.	esophagus
FAM175B promotes apoptosis by inhibiting ATF4 ubiquitination in esophageal squamous cell carcinoma.	FAM175B is a reported regulator of p53 and suppresses tumorigenesis in numerous types of cancer, but very little is known about its function in esophageal squamous cell carcinomas (ESCCs), almost 70% of which exhibit mutations in p53. Here, we report that FAM175B expression is downregulated in high-grade intraepithelial neoplasia (t = 2.44, P = 0.031) and ESCC (t = 5.664, P < 0.001) tissues relative to that in adjacent normal esophageal tissues. Exogenous expression of FAM175B in ESCC cells resulted in a decrease in proliferation rate, inhibition of colony formation, and an increase in apoptosis rate. Knockdown of FAM175B produced the opposite results. Furthermore, confocal microscopy and coimmunoprecipitation assay showed that Activating transcription factor 4 (ATF4) colocalized and interacted with FAM175B. Ubiquitination assays revealed that FAM175B inhibited ubiquitin-dependent ATF4 degradation and elevated ATF4 protein level. Finally, luciferase reporter experiments further clarified that FAM175B promoted CHOP expression in an ATF4-dependent manner. Accordingly, the proapoptotic activity of FAM175B was significantly rescued by treatment with si-ATF4 and the CHOP inhibitor 4-PBA. In summary, FAM175B inhibited ATF4 ubiquitination and promoted ESCC cell apoptosis in a p53-independent manner. FAM175B expression loss may be an early diagnostic biomarker in ESCC patients.	esophagus
MicroRNA-373 promotes the development of esophageal squamous cell carcinoma by targeting LATS2 and OXR1.	INTRODUCTION: MicroRNA373 was highly expressed in many tumors including esophageal cancer. However, its molecular mechanism is still unclear, especially epigenetic modification, in esophageal squamous cell carcinoma (ESCC). METHODS: In this study, we investigated serum levels of the miR-371-373 cluster in ESCC patients before and after surgical removal, and further focused on the expression level of miR-373-3p in tumor tissues of ESCC patients and its target genes. In addition, the epigenetic alterations of miR-373-3p promoter was analyzed. RESULTS: The expression levels of miR-371-5p and miR-373-3p were significantly increased in preoperative serum of ESCC patients compared with that of healthy volunteers (P<0.01); however, they dropped significantly after surgical removal (P<0.01). Compared with adjacent normal tissues, miR-373-3p also showed significant up-regulation in cancer tissues (P<0.05). The methylation levels of miR-373-3p promoter were 42.86% in ESCC cancer tissue and 66.67% in adjacent normal tissues. The low methylation of the miR-373-3p promoter may promote the expression of miR-373-3p. Large tumor suppressor 2 (LATS2) and oxidation resistance 1(OXR1) are predicted to be targets of miR-373-3p by the bioinformatics method. They are the genes in the Hippo and the p53 signaling pathway, respectively. Their respective upstream genes, neurofibromatosis type 2 (NF2) and Jun Kinase, and the downstream genes, transcriptional co-activator with PDZ-binding motif (TAZ) and caspase 9, were also detected. The expression of all these genes were significantly decreased in ESCC cancer tissues compared with adjacent normal tissues. CONCLUSIONS: This study shows that DNA epigenetic modification in the miR-373-3p promoter region and the Hippo and p53 signaling pathways play important roles during the miR-373-3p mediating ESCC development process.	esophagus
Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma.	OBJECTIVE: Current strategies to guide selection of neoadjuvant therapy in oesophageal adenocarcinoma (OAC) are inadequate. We assessed the ability of a DNA damage immune response (DDIR) assay to predict response following neoadjuvant chemotherapy in OAC. DESIGN: Transcriptional profiling of 273 formalin-fixed paraffin-embedded prechemotherapy endoscopic OAC biopsies was performed. All patients were treated with platinum-based neoadjuvant chemotherapy and resection between 2003 and 2014 at four centres in the Oesophageal Cancer Clinical and Molecular Stratification consortium. CD8 and programmed death ligand 1 (PD-L1) immunohistochemical staining was assessed in matched resection specimens from 126 cases. Kaplan-Meier and Cox proportional hazards regression analysis were applied according to DDIR status for recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total of 66 OAC samples (24%) were DDIR positive with the remaining 207 samples (76%) being DDIR negative. DDIR assay positivity was associated with improved RFS (HR: 0.61; 95% CI 0.38 to 0.98; p=0.042) and OS (HR: 0.52; 95% CI 0.31 to 0.88; p=0.015) following multivariate analysis. DDIR-positive patients had a higher pathological response rate (p=0.033), lower nodal burden (p=0.026) and reduced circumferential margin involvement (p=0.007). No difference in OS was observed according to DDIR status in an independent surgery-alone dataset.DDIR-positive OAC tumours were also associated with the presence of CD8+ lymphocytes (intratumoural: p<0.001; stromal: p=0.026) as well as PD-L1 expression (intratumoural: p=0.047; stromal: p=0.025). CONCLUSION: The DDIR assay is strongly predictive of benefit from DNA-damaging neoadjuvant chemotherapy followed by surgical resection and is associated with a proinflammatory microenvironment in OAC.	esophagus
Impact of pathologically assessing extranodal extension in the thoracic field on the prognosis of esophageal squamous cell carcinoma.	BACKGROUND: This study aimed to elucidate the impact of extranodal extension, pathologically assessed according to new diagnostic criteria, on the prognosis of esophageal squamous cell carcinoma. Extranodal extension has been shown to be a prognostic indicator for head and neck cancers; however, its utility in esophageal squamous cell carcinoma has not been demonstrated. METHODS: We enrolled 174 consecutive esophageal squamous cell carcinoma patients who had undergone esophagectomy with lymph node dissection in the three fields. Extranodal extensions from all metastatic lymph nodes were pathologically classified into grades 1-3. Then, relationships between extranodal extension and clinicopathologic factors, including overall survival and recurrence-free survival were examined. Recurrence patterns in the thoracic and abdominal fields were also examined. RESULTS: Kaplan-Meier analyses showed that patients with grades 2 and 3 extranodal extension showed significantly poorer recurrence-free survival compared with those with intranodal involvement of esophageal squamous cell carcinoma cells (P = .0041 and P = .0011, respectively). Patients with pN3b (newly defined in this study as including at least one lymph node with grade 2-3 extranodal extension regardless of region or number of metastatic lymph nodes) was associated with significantly shorter overall survival and recurrence-free survival (P < .001). Moreover, multivariate analyses indicated that patients with grades 2-3 extranodal extension showed significantly reduced recurrence-free survival in the thoracic but not in the abdominal field (thoracic: P = .047; abdominal: P = .15). CONCLUSION: This study suggests that the extranodal extension grading system proposed in this study is a novel predictor of overall survival and recurrence-free survival in esophageal squamous cell carcinoma.	esophagus
Glucose Drives Growth Factor-Independent Esophageal Cancer Proliferation via Phosphohistidine-Focal Adhesion Kinase Signaling.	"BACKGROUND & AIMS: Most targeted therapies against cancer are designed to block growth factor-stimulated oncogenic growth. However, response rates are low, and resistance to therapy is high. One mechanism might relate to the ability of tumor cells to induce growth factor-independent proliferation (GFIP). This project aims to understand how (1) cancer cells preferentially derive a major growth advantage by using critical metabolic products of glucose, such as phosphoenolpyruvate (PEP), to drive proliferation and (2) esophageal squamous cell carcinoma (ESCC) cells, but not esophageal adenocarcinoma cells, can induce GFIP by using glycolysis to activate phosphohistidine (poHis)-mediated signaling through focal adhesion kinase (FAK). METHODS: The hypothesis to be tested is that ESCC GFIP induced by glucose is facilitated by PEP-mediated histidine phosphorylation (poHis) of FAK, leading to the possibility that ESCC progression can be targeted by blocking poHis signaling. Biochemical, molecular biological, and in vivo experiments including bromodeoxyuridine/5-ethynyl-2'-deoxyuridine labeling, radioisotope tracing, CRISPR gene editing, and analysis of signaling gene sets in human cancer tissues and xenograft models were performed to define the mechanisms underlying ESCC GFIP. RESULTS: Glucose promotes growth factor-independent DNA replication and accumulation of PEP in ESCC cells. PEP is the direct phospho-donor to poHis58-FAK within a known ""HG"" motif for histidine phosphorylation. Glucose-induced poHis58 promotes growth factor-independent FAK-mediated proliferation. Furthermore, glucose activates phosphatidylinositol-3'-kinase/AKT via poHis58-FAK signaling. Non-phosphorylatable His58A-FAK reduces xenograft growth. CONCLUSIONS: Glucose induces ESCC, but not esophageal adenocarcinoma GFIP via PEP-His58-FAK-AKT signaling. ESCC progression is controlled by actionable growth factor-independent, glucose-induced pathways that regulate proliferation through novel histidine phosphorylation of FAK."	esophagus
Identification of esophageal cancer pathway deviation and construction of a diagnosis model using three kernel genes.	The purpose of this study is to better understand the role of interleukin 35 (IL35) in esophageal carcinoma by comparing the mRNA level in Barrett's esophageal mucosa and in matched normal squamous mucosa and to understand how the diagnosis model works with two other genes: hepatocyte nuclear factor 1B (HNF1B) and cAMP responsive element binding protein 3-like 1 (CREB3L1). By comparing carcinoma tissue and normal tissue samples, we extracted all the differentially expressed mRNAs. The bioinformatics analysis resulted in the discovery of three prominent genes. Eventually, the three genes were utilized to train a deep-learning model. An additional wet experiment was conducted to validate the effect of IL35. All the differentially expressed genes were enriched into nine groups, each of which has specific biological functions. Given that the three significant genes HNF1B, CREB3L1, and IL35 as diagnostic features, a deep-learning model was constructed, reaching an accuracy of 93% in the training set and 87% in the test set. Our findings suggest that IL35, along with the other two signatures, can distinguish esophageal tumor samples from normal samples precisely.	esophagus
Hematologic Markers as Prognostic Factors in Nonmetastatic Esophageal Cancer Patients under Concurrent Chemoradiotherapy.	Nonmetastatic esophageal cancer can demonstrate a high local recurrence rate even under the standard treatment. We evaluated platelet counts before and after concurrent chemoradiotherapy (CCRT), neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio for predicting esophageal cancer prognosis under CCRT. Newly diagnosed patients with esophageal cancer (stages IA-IIIC) who underwent CCRT during January 2013-December 2017 were enrolled. The data were collected retrospectively. Overall survival (OS), time to progressive disease (TPD), and time to metastasis (TM) were recorded for indicating prognosis. Kaplan-Meier curves were plotted and univariate and multivariate analyses were performed. In total, 105 patients were enrolled. The stages of esophageal cancer and surgery were associated with prognosis (i.e., OS, TPD, and TM). Based on TPD and TM, women had better prognosis than men. In the univariate analysis, high pre- and post-CCRT platelet counts (>300,000/μL), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) as well as low lymphocyte percentage were significantly associated with poor prognosis. However, in the multivariate analysis, only post-CCRT high platelet count (>300,000/μL) remained significantly associated with poor prognosis (P = .041, .045, and .023 for OS, TPD, and TM, respectively). Poor prognosis was observed in patients with high platelet counts, PLR, NLR, and low lymphocyte percentage. Surgery was an independent factor predicting better prognosis. Our findings may have clinical significance with regard to therapeutic decision-making.	esophagus
The Current Status of Immunotherapies in Esophagogastric Cancer.	This review summarizes completed and ongoing studies evaluating the activity of immune checkpoint inhibitors in esophagogastric cancer.	esophagus