crossing96/oncoscreening huggingface dataset:
OTUB1 promotes esophageal squamous cell carcinoma metastasis through modulating Snail stability.	Snail is a key regulator of epithelial-mesenchymal transition (EMT) and plays an important role in tumor progression and metastasis. Snail is rapidly degraded in the cells and its protein level is critically controlled. Although several E3 ligases regulating Snail degradation have been defined, the deubiquitinases (DUBs) responsible for Snail deubiquitination are less studied. We identified ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 (OTUB1) as a DUB that stabilizes Snail through preventing its ubiquitination and proteasomal degradation. Functionally, OTUB1 facilitates metastasis of esophageal squamous cell carcinoma (ESCC) through promoting Snail protein stability. Moreover, OTUB1 is highly expressed in ESCC and higher expression of OTUB1 predicts poor prognosis. These findings suggest that OTUB1 is an essential regulator of Snail and plays a critical role in facilitating esophageal cancer progression.	esophagus
ISG15 promotes esophageal squamous cell carcinoma tumorigenesis via c-MET/Fyn/β-catenin signaling pathway.	Esophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors in China with a poor prognosis. Most ESCC patients were diagnosed at advanced stages, losing the opportunity for surgical excision. Hence, it remains a pressing work to identify biomarkers for early detection, prognosis prediction and targeting therapies in ESCC. Interferon-stimulated gene 15 (ISG15) encodes a 15-kDa protein, and is involved in the post-translational modification (PTMs) of multiple proteins. However, the molecular functions of ISG15 in ESCC remain unclear. In this work, we found that ISG15 was aberrantly expressed in ESCC tissues and cell lines. Enhanced protein level of ISG15 promoted cellular malignant phenotypes including proliferation, migration, invasion and tumor formation in vivo. Consistently, reduction of ISG15 attenuated the cellular malignant phenotype in ESCC cell lines. Furthermore, gene-expression profiles suggested that the differentially expressed ISG15 affected the expression of a panel of genes enriched in the cell adherens junction, such as c-MET. Notably, as a secreted protein, the concentration of ISG15 was elevated in ESCC plasma than healthy individuals, acting as a potential diagnostic marker. Taken together, our results suggested a tumor promotion role of ISG15 in ESCC via c-MET/Fyn/β-catenin pathway.	esophagus
Inequalities in esophageal cancer mortality in Brazil: Temporal trends and projections.	The main objective of the study was to analyze the effect of age, period and birth cohort on esophageal cancer mortality in Brazil and its geographic regions, per sex. An ecological study is presented herein, which evaluated the deaths by esophageal cancer and the distribution, per geographic region. Poisson Regression was utilized to calculate the effects of age, period and birth cohort, and projections were made with the statistical software R, using the age-period-cohort model. Projection of data covered the period 2015-2029. Regarding the geographic regions of Brazil, a decrease was verified, throughout time, for the mortality rates of the South and Southeast regions, for men and women. For the North, Northeast and Midwest regions, an increase was evidenced in mortality rates, mainly for men, after the 2000's. Regarding the projections, a progressive increase of mortality rates was verified for the Northeast and North regions. Divergences evidenced for observed and projected esophageal cancer mortality rates revealed inequalities among the geographic regions of Brazil.	esophagus
Sequestosome 1 protects esophageal squamous carcinoma cells from apoptosis via stabilizing SKP2 under serum starvation condition.	Esophageal squamous cell carcinoma (ESCC) is one of the malignancies in digestive system, with a low 5-year survival rate. We previously revealed that Sequestosome 1 (SQSTM1/p62) protein levels were upregulated in ESCC tissues. However, it is unclear about the function of p62 and the underlying mechanism. Here, we used immunofluorescence and immunohistochemistry to investigate the expression of p62 in ESCC. Western blotting, quantitative RT-PCR, colony formation assay, flow cytometry, immunoprecipitation and xenograft tumor assay were used to analyze the role of p62 in vitro and vivo. Here, we showed that p62 serves as a regulator of cell apoptosis under serum starvation condition in ESCC cells. Through activating the protein kinase C iota (PKCiota)-S-phase kinase-associated protein 2 (SKP2) signaling pathway, p62 enhances cell apoptosis resistance and colony formation in vitro and tumor growth in mouse models. Through interaction with the domains PB1, p62 upregulated the expression of PKCiota and then depressed the ubiquitin-mediated proteasomal degradation of SKP2. p62-silencing combined with a PKCiota inhibitor ATM significantly enhanced cell apoptosis and inhibited cell survival. Immunohistochemical analysis revealed a positive association between the expression of p62 and SKP2 in primary ESCC tissues. And importantly, p62 presented a markedly cytoplasmic translocation in cancerous cells, including in 16 (30.76%) tumors at stage T1, as compared with its nuclear location in normal esophageal epithelial cells. In summary, p62 plays an anti-apoptotic role in ESCC cells via stabilizing SKP2 under serum starvation condition. These data suggest that p62 might be an early biomarker and a candidate therapeutic target of ESCC.	esophagus
The optimal lymph node dissection in patients with adenocarcinoma of the esophagogastric junction.	OBJECTIVE: The aim of this study was to refine the optimal lymph node dissection in Western patients with adenocarcinoma of the esophagogastric junction (AEG). BACKGROUND: Lymphadenectomy is essential in addition to surgery for AEG. Asian studies continually present superior survival rates using a more extended lymphadenectomy compared with results reproduced in the West. Thus, the optimal extend of the lymphadenectomy remains unclear in Western patients. METHODS: A retrospective cohort was conducted of patients with AEG from January 1st, 2003 to December 31st, 2011. All patients undergoing curatively intended surgery was included. Two types of resections were constructed; Res1 included patients where only the loco regional lymph nodes were removed (station 1-4, 7 and 9) and Res2 included the additional removal of the more distant stations 8 and/or 11. RESULTS: We identified 510 patients with AEG. The highest frequency of lymph node metastases was seen in the loco regional stations 1-3, 7 and 9, ranging from 34% to 41.4%. There was no difference in overall survival between the two groups; the median survival rate for Res1 was 30.4 months compared to 24.1 months for Res2 (p = 0.157). Furthermore, the extend of lymph node dissection seemed to have no effect on survival (HR = 1.061, 95%CI 0.84-1.33). CONCLUSION: No significant difference in survival between the extended and the less extended lymphadenectomy was found. The presence of metastases in distant lymph nodes indicates poor survival and may represent disseminated disease. We do not find evidence that supports an extended lymph node dissection in Western patients.	esophagus
Predictive biomarkers for the treatment of resectable esophageal and esophago-gastric junction adenocarcinoma: from hypothesis generation to clinical validation.	Esophageal and esophago-gastric junction (EGJ) adenocarcinomas remain a major health problem worldwide with a worryingly increasing incidence. Recent trials indicate survivals benefit for preoperative or perioperative chemoradiotherapy compared to surgery alone. Beside standard chemoradiotherapy regimens, new therapeutic approaches with targeted therapies have been proposed for the treatment of resectable disease. However, clinical outcomes remain extremely poor due to drug resistance phenomena. The failure of these approaches could be partially ascribed to their incorrect application in patients. Therefore, the identification of strong biomarkers for optimal patient management is urgently needed. Areas covered: This review aims to summarize and critically discuss the most relevant findings regarding predictive biomarker development for neoadjuvant treatment of resectable esophageal and esophago-gastric junction adenocarcinoma patients. Expert commentary: Optimizing the currently available therapeutic modalities through a more accurate selection of patients may avoid the use of ineffective and potentially toxic treatments. During the last decade, the advent of high-throughput '-omics' technologies has set the basis for a new biomarker discovery approach from 'molecule by molecule' screening towards a large-scale systematic screening process with exponential increases in putative biomarkers, which often failed to provide adequate clinical validation.	esophagus
The role of surgical treatment in isolated organ recurrence of esophageal cancer-a systematic review of the literature.	BACKGROUND: Despite the improvements in the early detection and treatment of non-metastatic esophageal cancer, more than half of patients undergoing a curative treatment for esophageal cancer will develop recurrence within three years. The prognosis of these patients is poor. However, a wide range in overall survival has been reported, depending on the pattern of recurrence, and no optimal treatment strategy following recurrence has yet been uniformly accepted. AIM: In this article, we aimed to systematically review the literature for the role of surgical resection of metachronous distant metastasis following primary treatment of esophageal cancer. Furthermore, we discuss possible factors that could possibly predict which patients may benefit from a surgical approach. A comprehensive literature search was conducted in PubMed using combinations of keywords. RESULTS: Patients with recurrence may benefit of a multimodality treatment. Regarding the isolated recurrence of esophageal cancer in solid visceral organs, operative intervention has been proposed as a treatment that may offer a survival benefit in an individual basis. No definitive conclusions regarding the potential survival advantage offered by the surgical treatment of solitary recurrent lesions can be drawn. However, recent improvements in surgical treatment and optimization of perioperative management guarantee an acceptable operative risk, making surgical resection of solitary recurrence lesions a considerable therapeutic option. CONCLUSIONS: It can be conferred from the available studies that the surgical treatment of isolated recurrence from esophageal cancer may offer a survival benefit for properly selected patients. Prospective, multicenter studies might be useful to gain a better insight into those factors that affect selection of patients to take benefit from an operative intervention.	esophagus
Elevated cancer risk perceptions among patients with Barrett's esophagus: do psychological factors play a role?	Barrett's esophagus is a chronic esophageal condition that is associated with an increased risk of esophageal adenocarcinoma. This chronic condition negatively impacts patients' quality of life and is associated with increased levels of psychological distress. In 'Perceptions of risk and therapy among patients with Barrett's esophagus: a patient survey study,' Stier et al. explored factors associated with esophageal cancer risk perception and management decisions among patients with Barrett's esophagus. The results indicate that patients greatly overestimate their cancer risk and are willing to accept low success rates and high risks of complications to undergo endoscopic therapy. These findings are important and contribute to our understanding of patient risk perceptions in this population. However, psychological factors were not considered in this study and are potentially important patient characteristics influencing risk perceptions. Anxiety in particular warrants more attention in this population. Furthermore, the study findings indicate that patients have a strong preference for communicating with their physician regarding disease information. Therefore, greater emphasis on patient-centered communication strategies during conversations about Barrett's esophagus and cancer risk may be helpful for reducing patients' psychological distress and engaging patients in shared decision making regarding management strategies.	esophagus
Comparison of short-term outcomes between robot-assisted minimally invasive esophagectomy and video-assisted minimally invasive esophagectomy in treating middle thoracic esophageal cancer.	Whether the robot-assisted minimally invasive esophagectomy (RAMIE) has any advantages over the video-assisted minimally invasive esophagectomy (VAMIE) remains controversial. In this study, we tried to compare the short-term outcomes of RAMIE with that of VAMIE in treating middle thoracic esophageal cancer from a single medical center. Consecutive patients undergoing RAMIE or VAMIE for middle thoracic esophageal cancer from April 2016 to April 2017 were prospectively included for analysis. Baseline data and pathological findings as well as short-term outcomes of these two group (RAMIE group and VAMIE group) patients were collected and compared. A total of 84 patients (RAMIE group: 42 patients; VAMIE group: 42 patients) were included for analysis. The baseline characteristics between the two groups were comparable. RAMIE yielded significantly larger numbers of total dissected lymph nodes (21.9 and 17.8, respectively; P = 0.042) and the right recurrent laryngeal nerve (RLN) lymph nodes (2.1 and 1.2, respectively; P = 0.033) as well as abdominal lymph nodes (10.8 and 7.7, respectively; P = 0.041) than VAMIE. Even though RAMIE may consume more overall operation time, it could significantly decrease total blood loss compared to VAMIE (97 and 161 mL, respectively; P = 0.015). Postoperatively, no difference of the risk of major complications or hospital stay was observed between the two groups. In conclusion, RAMIE had significant advantage of lymphadenectomy especially for dissecting RLN lymph nodes over VAMIE with a comparable rate of postoperative complications. Further randomized controlled trials are badly needed to confirm and update our conclusions.	esophagus
Dek overexpression in murine epithelia increases overt esophageal squamous cell carcinoma incidence.	Esophageal cancer occurs as either squamous cell carcinoma (ESCC) or adenocarcinoma. ESCCs comprise almost 90% of cases worldwide, and recur with a less than 15% five-year survival rate despite available treatments. The identification of new ESCC drivers and therapeutic targets is critical for improving outcomes. Here we report that expression of the human DEK oncogene is strongly upregulated in esophageal SCC based on data in the cancer genome atlas (TCGA). DEK is a chromatin-associated protein with important roles in several nuclear processes including gene transcription, epigenetics, and DNA repair. Our previous data have utilized a murine knockout model to demonstrate that Dek expression is required for oral and esophageal SCC growth. Also, DEK overexpression in human keratinocytes, the cell of origin for SCC, was sufficient to cause hyperplasia in 3D organotypic raft cultures that mimic human skin, thus linking high DEK expression in keratinocytes to oncogenic phenotypes. However, the role of DEK over-expression in ESCC development remains unknown in human cells or genetic mouse models. To define the consequences of Dek overexpression in vivo, we generated and validated a tetracycline responsive Dek transgenic mouse model referred to as Bi-L-Dek. Dek overexpression was induced in the basal keratinocytes of stratified squamous epithelium by crossing Bi-L-Dek mice to keratin 5 tetracycline transactivator (K5-tTA) mice. Conditional transgene expression was validated in the resulting Bi-L-Dek_K5-tTA mice and was suppressed with doxycycline treatment in the tetracycline-off system. The mice were subjected to an established HNSCC and esophageal carcinogenesis protocol using the chemical carcinogen 4-nitroquinoline 1-oxide (4NQO). Dek overexpression stimulated gross esophageal tumor development, when compared to doxycycline treated control mice. Furthermore, high Dek expression caused a trend toward esophageal hyperplasia in 4NQO treated mice. Taken together, these data demonstrate that Dek overexpression in the cell of origin for SCC is sufficient to promote esophageal SCC development in vivo.	esophagus
Clinical values of Ku80 upregulation in superficial esophageal squamous cell carcinoma.	Ku80 is an important DNA repair protein. Here, this study sought to investigate clinical impacts of Ku80 expression for patients with superficial esophageal squamous cell carcinoma (ESCC). Immunohistochemical analysis of Ku80 expression was carried out in normal esophageal mucosa, squamous epithelial dysplasia, carcinoma in situ, and superficial ESCC. Its relationships with clinicopathological features and survival of superficial ESCC patients were further clarified. Lentivirus-mediated RNA interference was used to silence Ku80 gene in ECA109 and KYSE150 cells. Both quantitative real-time PCR and Western blot were employed to evaluate Ku80 levels. CCK-8 assay, clone formation assay, flow cytometry, and tumorigenesis experiment were performed to evaluate the malignant phenotype of ECA109 and KYSE150 cells. Increased Ku80 expression was observed in dysplastic esophageal mucosa and carcinoma in situ compared to normal esophageal mucosa (P < 0.001, P < 0.001). Ku80 expression was further increased in superficial ESCC in comparison with dysplastic esophageal mucosa and carcinoma in situ (P < 0.001, P = 0.034). In superficial ESCC, Ku80 overexpression was related to tumor differentiation (P = 0.017), T status (P = 0.011), nodal involvement (P = 0.005), TNM stage (P = 0.004), and postoperative recurrence (P = 0.008). Cox proportional hazards regression showed tumor differentiation, T status, nodal involvement, TNM stage, and Ku80 expression were both independent predictors of patients' overall survival and disease-free survival. Ku80 shRNA effectively reduced Ku80 expression, which significantly inhibited proliferation, clone formation, and induced apoptosis in ECA109 and KYSE150 cells. The tumor growth of xenografts was significantly reduced by Ku80 silencing in ECA109 and KYSE150 cells. Ku80 overexpression associates with unfavorable prognosis of superficial ESCC patients, and silencing of Ku80 could inhibit the malignant behavior of ESCC cells. We provide evidence that Ku80 has unrecognized roles in carcinogenesis and development of ESCC.	esophagus
Four cancer cases after esophageal atresia repair: Time to start screening the upper gastrointestinal tract.	Esophageal atresia (EA) is one of the most common congenital digestive malformations and requires surgical correction early in life. Dedicated centers have reported survival rates up to 95%. The most frequent comorbidities after EA repair are dysphagia (72%) and gastroesophageal reflux (GER) (67%). Chronic GER after EA repair might lead to mucosal damage, esophageal stricturing, Barrett's esophagus and eventually esophageal adenocarcinoma. Several long-term follow-up studies found an increased risk of Barrett's esophagus and esophageal carcinoma in EA patients, both at a relatively young age. Given these findings, the recent ESPGHAN-NASPGHAN guideline recommends routine endoscopy in adults born with EA. We report a series of four EA patients who developed a carcinoma of the gastrointestinal tract: three esophageal carcinoma and one colorectal carcinoma in a colonic interposition. These cases emphasize the importance of lifelong screening of the upper gastrointestinal tract in EA patients.	esophagus
High lymphocyte count during neoadjuvant chemoradiotherapy is associated with improved pathologic complete response in esophageal cancer.	BACKGROUND AND PURPOSE: Neoadjuvant chemoradiation (nCRT) can reduce tumor infiltrating lymphocytes. We examined absolute lymphocyte count (ALC) nadir during nCRT for esophageal cancer (EC) and pathologic complete response (pCR). MATERIALS AND METHODS: Patients with stage I-IVA EC (n = 313) treated 2007-2013 with nCRT followed by surgery were analyzed. ALC was obtained before, during/weekly, and one month after CRT. pCR was defined as no viable tumor cells at surgery. High ALC was defined as nadir of ≥0.35 × 10(3)/μL (highest tertile). Comparison of continuous and categorical variables by pCR was assessed by ANOVA and Pearson's chi-square. Univariate/multivariate logistic regression was used to assess predictors of pCR and high ALC nadir. RESULTS: Eighty-nine patients (27.8%) achieved a complete pathological response (pCR). For patients with pCR, median ALC nadir was significantly higher than those without (0.35 × 10(3)/μL vs 0.29 × 10(3)/μL, p = 0.007). Patients maintaining high ALC nadir had a higher pCR rate (OR1.82, 95%CI 1.08-3.05, p = 0.024). Predictors of high ALC included treatment with proton therapy vs. IMRT (OR4.18, 95%CI 2.34-7.47, p < 0.001), smoking at diagnosis (OR2.80, 95%CI 1.49-5.25, p = 0.001), early stage I-II disease (OR2.33, 95%CI 1.32-4.17, p = 0.005), and SCC histology (OR3.70, 95%CI 1.01-14.29, p = 0.048). Mean body dose (MBD) was inversely related to high ALC nadir (OR0.77 per Gy, 95%CI 0.70-0.84, p < 0.001). CONCLUSION: A higher ALC level during nCRT is associated with a higher rate of pCR for esophageal cancer patients undergoing trimodality therapy.	esophagus
Contrast-enhanced swallow study sensitivity for anastomotic leak detection in post-esophagectomy patients.	INTRODUCTION AND AIMS: Esophagectomy is a highly invasive surgery and one of its postoperative complications is anastomotic leakage, occurring in 53% of cases. The aim of the present study was to determine the sensitivity of the contrast-enhanced swallow study as a method for diagnosing anastomotic leak in patients that underwent esophagectomy. MATERIAL AND METHODS: The present retrospective study included the case records of patients that underwent esophagectomy with reconstruction and cervical anastomosis at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán within the time frame of January 1, 2000 and May 31, 2016. Demographic, clinical, and laboratory data emphasizing clinical and radiographic anastomotic leak detection were identified. Descriptive statistics were carried out and contrast-enhanced swallow study sensitivity for diagnosing leakage was calculated. RESULTS: Seventy patients were included in the analysis. The mean age of the patients was 50.6 years, 51 of the patients were men (72.86%), and 19 were women (27.14%). Indications for surgery were benign lesion in 29 patients (41.4%) and malignant lesion in 41 (58.6%). A total of 44.3% of the patients presented with a comorbidity, with diabetes mellitus and high blood pressure standing out. Thirty patients (42.85%) presented with anastomotic leak. Contrast-enhanced swallow study sensitivity for leak detection was 43.33%. CONCLUSIONS: The diagnostic sensitivity of the contrast-enhanced swallow study was very low. Therefore, we recommend the discontinuation of its routine use as a method for diagnosing anastomotic leaks.	esophagus
Evaluation and management of Non-variceal upper gastrointestinal bleeding.	Non-variceal upper gastrointestinal bleeding continues to be an important cause of morbidity and mortality. The most common causes include peptic ulcer disease, Mallory-Weiss syndrome, erosive gastritis, duodenitis, esophagitis, malignancy, angiodysplasias and Dieulafoy's lesion. Initial assessment and early aggressive resuscitation significantly improves outcomes. Upper gastrointestinal endoscopy continues to be the gold standard for diagnosis and treatment. We present a comprehensive review of literature for the evaluation and management of non-variceal upper gastrointestinal bleeding.	esophagus