crossing96/oncoscreening huggingface dataset:
Incidence of MSI-H esophageal carcinoma and related identification of genomic alterations: A multi-center real-world study.	Microsatellite instability-high (MSI-H) is a favorable prognostic factor for neoadjuvant chemotherapy in several solid tumors, and large datasets are needed to provide robust evidence of its prognostic value in esophageal carcinoma (EC). We aimed to determine the incidence of MSI-H tumors in patients with EC and identify genomic alterations in MSI-H tumors. Data were obtained from three centers in China: Nanjing Drum Tower Hospital, Beijing Cancer Hospital, and the Cancer Hospital Chinese Academy of Medical Sciences. From June 2023 to December 2024, 1485 patients with EC were enrolled in this study. We investigated the incidence of MSI-H tumors and performed whole-exome sequencing of MSI-H tumor tissues. There were three patients with MSI-H from three centers (3/614, 0.49%) in Nanjing Drum Tower Hospital, five (5/644, 0.78%) in Beijing Cancer Hospital, and four (4/227, 1.76%) in the Cancer Hospital Chinese Academy of Medical Sciences. Among the 12 MSI-H tumor tissues, 6 were esophageal squamous cell carcinoma (ESCC) and 6 were esophageal adenocarcinoma (EAC). All MSI-H tumor tissues showed loss of PMS2 expression (100%), with concurrent loss of MLH1 in 9 (75%). Among the MSI-H tumors subjected to Whole Exome Sequencing (WES), all demonstrated high tumor mutation burden (TMB: 19.12-32.68 mutations/Mb) and harbored multiple somatic mutations. The consistency of MSI-H and high TMB scores showed that MSI-H could be an indicator of receiving immunotherapy in EC patients.	esophagus
Copy number amplification of TTPAL promotes cholesterol biosynthesis and esophageal squamous cell carcinoma progression via elevating NSUN2-mediated m5C modification of SREBP2 mRNA.	Alterations in copy number are crucial genetic events in the development of esophageal squamous cell carcinoma (ESCC). Here, we show that Tocopherol alpha transfer protein-like (TTPAL) is highly amplified and frequently overexpressed in human ESCC. Using Ttpal-KO mouse mode, we demonstrate that TTPAL promotes ESCC cell proliferation and accelerates tumor development by driving cholesterol biosynthesis. Mechanistically, TTPAL upregulates a key transcription factor in cholesterol biosynthesis-sterol regulatory element-binding transcription factor (SREBP2) in ESCC cells. TTPAL interacts with the RNA methyltransferase NSUN2 and relieves the ubiquitination of NSUN2, protecting NSUN2 from proteasome-mediated degradation. In turn, NSUN2 catalyzes the m5C modification of SREBP2 mRNA, and then the m5C modified SREBP2 mRNA binds to the m5C reader protein-ALYREF to enhance its stability, thereby increasing SREBP2 expression. Moreover, we validate the efficacy of cholesterol biosynthesis inhibitor simvastatin in ESCC with high TTPAL expression. Overall, our results uncover a novel function of TTPAL in regulating SREBP2 expression, revealed a previously unknown TTPAL/NSUN2/SREBP2 pathway that promotes cholesterol biosynthesis in ESCC cells, and identified sensitively to cholesterol biosynthesis inhibitor simvastatin.	esophagus
The AP-1 factor JUNB correlates with poor survival of patients with esophageal adenocarcinoma.	Malignant cells have in contrast to non-transformed cells de-regulated transcriptional networks. The activator protein-1 (AP-1) transcription factor complex is expressed in many cancer entities including adenocarcinomas and has been correlated to de-regulated transcription and tumor-promoting mechanisms. Despite complex treatment approaches, esophageal cancer is still associated with poor overall survival. There is an urgent need for better patient stratification to increase the outcome of the multimodal treatment. This study investigated the expression of two AP-1 factors, cJUN and JUNB, and their role in 735 patients with esophageal cancer undergoing surgery. We performed immunohistochemical stainings for cJUN and JUNB and correlated the expression to the clinical outcome. Patients with a high JUNB expression level correlate to a reduced overall survival (OS) compared to patients with a low expression. Furthermore, in the multivariate analysis high JUNB expression was shown to be an independent risk factor for reduced patient survival. In addition, subgroup analysis demonstrated a significantly reduced OS for high JUNB expression in the subgroup of patients with neoadjuvant treatment. Strikingly, tumors co-expressing cJUN and JUNB were associated with poorer overall survival compared to those expressing only one or neither of the transcriptions factors. Our study suggests JUN expression as a novel biomarker to stratify patients, especially in the subgroup of neoadjuvant treated patients. Our findings have translational implications as targeting JUN might complement current available multimodal treatment approaches.	esophagus
Re-evaluating Stem Cell Roles in Homeostasis and Cancer of the Esophagus.	The localization and identity of esophageal stem cells remain highly debated, prompting the emergence of several hypotheses. Although early models proposed a homogeneous basal progenitor layer, recent evidence suggests a heterogeneous pool of stem/progenitor cells with diverse phenotypic and functional characteristics. We present a perspective on this heterogeneity and its implications for both normal tissue maintenance and disease susceptibility. Esophageal cancers can emerge as a result of random mutations or the activity of cancer stem cells (CSCs). The multifaceted interactions between genetic predisposition and environmental influences demonstrate that cancer onset can be driven not only by cell phenotype but also by various external pressures. Advances in in vivo and in vitro models now offer valuable tools to explore these stem cell dynamics and may pave the way for novel therapeutic approaches in esophageal cancer treatment.	esophagus
YAP as a therapeutic target in esophageal squamous cell carcinoma: insights and strategies.	BACKGROUND: Yes-associated protein (YAP) is a core component of the Hippo pathway, which functions as an oncogene in various cancers. However, emerging evidence has shown that YAP can also act as a tumor suppressor. Therefore, understanding the function and molecular mechanism of YAP is crucial for developing YAP-targeted drugs in tumors. METHODS: A comprehensive literature review was conducted. The review mainly includes the post-translational modification, the regulatory mechanisms and function of YAP in esophageal squamous cell carcinoma (ESCC). RESULTS: YAP undergoes various post-translational modifications (PTMs), including phosphorylation, ubiquitination, acetylation and others, which critically regulate its protein stability and transcriptional activity in multiple tumors, particularly ESCC. YAP is highly expressed in ESCC tissues, with its aberrant activation closely correlated with poor prognosis in patients. Additionally, YAP is involved in the progression of ESCC, including tumor migration, invasion, proliferation, cell stemness, apoptosis, therapeutic resistance, and immunity. In ESCC, YAP has been confirmed to be regulated by multiple upstream regulators, such as E3 ubiquitin ligases and kinases, thereby influencing the ESCC progression. However, there are still few drugs available clinically for YAP-targeted therapy, which requires further research. In this review, we systematically synthesize the biological roles and regulatory mechanisms of YAP in ESCC and outline potential research directions for YAP-targeted therapies, aiming to provide novel insights for precision medicine in ESCC. CONCLUSION: YAP is closely correlated to ESCC progression, and it could be a promising target for ESCC treatment.	esophagus
Global burden of esophageal diseases: a comprehensive analysis of disease trends and risk factors from 1990 to 2021.	BACKGROUND: Esophageal diseases (ED) are a common category of upper gastrointestinal disorders, mainly including gastroesophageal reflux disease (GERD), esophagitis, Barrett's esophagus, achalasia, and esophageal cancer (EC). In recent years, the high recurrence rate of GERD and poor prognosis of EC are paid more attention, collectively contributing to the global burden of ED. METHODS: For this study, we systematically analyzed the global distribution of ED from 1990 to 2021, detailing the burden across different countries, regions, and socio-demographic index (SDI) levels. Furthermore, we explored temporal trends in ED burden over this period and conducted decomposition analysis, health inequality analysis, and frontier analysis. Finally, we projected trends in ED burden from 2022 to 2045, and quantify contributions of associated risk factors to disability-adjusted life years (DALYs) of EC. RESULTS: The absolute numbers of incidence, mortality, and DALYs for GERD and EC showed increasing trends from 1990 to 2021, while their age-standardized rates (ASRs) demonstrated divergent patterns: stable for GERD and declining for EC. The highest ASRs were observed in low-middle SDI regions for GERD and high-middle SDI regions for EC, respectively, with population as a main driver. If current trends continue, the burden of GERD will continue to rise, whereas that of EC will persistently decline by 2045. In 2021, DALYs of EC were mainly attributed to smoking (36.5%) and alcohol use (16.2%). CONCLUSIONS: For GERD and EC, the global burden continued to rise and decline from 1990 to 2021, respectively. Developing targeted public health strategies in different countries and regions is crucial for alleviating the global burden of ED.	esophagus
Aberrant Notch-signaling promotes tumor angiogenesis in esophageal squamous-cell carcinoma.	Esophageal squamous-cell carcinoma (ESCC) is one of the most common gastrointestinal cancers in China, characterized by high malignancy and poor prognosis. Nowadays, the therapeutic options for this cancer are very limited. Notch-signaling is often overactivated in ESCC, but its role remains to be fully elucidated. Here, we demonstrate that aberrant Notch-signaling plays an important role in tumor angiogenesis. In clinical ESCC samples, Notch-signaling activation scores were significantly correlated with tumor microvascular density, advanced TNM stages, and short patient survival time. Silencing Notch-signaling substantially suppressed the ability of ESCC cells to promote angiogenesis in vitro and in vivo. By integrating analysis of CUT&Tag and RNA sequencing data, we identified ubiquitin-specific protease 5 (USP5) as a Notch-signaling downstream effector that is transcriptionally upregulated by the NOTCH1 intracellular domain (NICD1)-RBPJ complex and mediates tumor angiogenesis. USP5 stabilized STAT3 via its deubiquitination function, thereby enhancing the production of pro-angiogenic factors by cancer cells, including VEGF, ANGPT2, and CXCL1. We showed that chemotherapy combined with the USP5 inhibitor can additionally repress tumor growth and angiogenesis in mice. These findings explain why ESCC cells have much fewer NOTCH1 mutations than normal and precancerous epithelium, reveal a novel mechanism for Notch-signaling to drive tumor angiogenesis via the NOTCH1-USP5-STAT3 axis, and open a potential new avenue for anti-tumor angiogenesis therapy.	esophagus
Development and validation of a nomogram model to predict postoperative delirium after resection of esophageal cancer.	The study aimed to establish and validate a nomogram model to predict postoperative delirium (POD) among esophageal cancer resection patients. Clinical data of 396 patients with esophageal cancer who underwent esophagectomy from November 2020 to June 2023 in the electronic medical records of cardiothoracic Surgery, Affiliated Hospital of Jiangnan University. Participants were randomly divided into training and testing sets in a 7:3 ratio. Predictors were screened by Least absolute shrinkage and selection operator (LASSO) regression analysis and a nomogram model was built. The discrimination and consistency of the model were evaluated using the area under the receiver operating characteristic curve (AUC), C-statistic, Brier score, Hosmer-Lemeshow goodness-of-fit test, calibration curve and decision curve analysis (DCA). The results were validated using 1000 bootstraps resampling internal validation and testing set. Among 32 potential predictors, the final prediction model included 6 variables: postoperative pain, postoperative infection, dexmedetomidine use, propofol use, duration of mechanical ventilation, and Prognostic Nutritional Index (PNI). The model showed a good discrimination with an AUC of 0.919 (95% CI: 0.885- 0.953) in the training set, and adjusted to 0.911 (95% CI: 0.878- 0.944) and 0.871 (95% CI: 0.802- 0.940) in the internal validation and the testing set, respectively. ROC curves, calibration curves, DCA curves, C-statistic, Brier score and Hosmer-Lemeshow goodness-of-fit test showed excellent model performance. This study successfully established and validated the first POD prediction model for patients with esophageal cancer resection. It could accurately predict the occurrence of POD and effectively identify the high-risk patients, which is of great significance for improving the risk stratification of the population and for implementing targeted prevention intervention measures.	esophagus
Preoperative sarcopenia predicts complications and non-cancer specific mortality in esophageal cancer surgery.	Sarcopenia, a condition characterized by decreased muscle mass and strength, has been reported to worsen the prognosis of patients with malignancies potentially. However, its impact on short- and long-term outcomes after esophagectomy for esophageal cancer remains unclear. This study aimed to investigate the influence of preoperative sarcopenia on postoperative complications and survival outcomes after esophagectomy. This retrospective study included 187 patients with esophageal cancer who underwent curative esophagectomy at our hospital between 2014 and 2023. Patients were classified into sarcopenia and non-sarcopenia groups based on their preoperative skeletal muscle index (SMI) measured using bioelectrical impedance analysis (BIA). The relationships between sarcopenia and short- and long-term outcomes were analyzed. Sarcopenia was identified in 43.9% (n = 82) of the patients. The sarcopenia group had a significantly higher incidence of postoperative pneumonia than the non-sarcopenia group (31.7% vs. 13.3%, P = 0.004). Survival analysis revealed that the sarcopenia group exhibited poorer overall survival (OS) and non-cancer-specific survival (NCSS) than the non-sarcopenia group. Multivariate analysis demonstrated that sarcopenia was an independent risk factor for postoperative pneumonia in the short term (odds ratio: 2.805, P = 0.007), as well as for poor OS (hazard ratio: 1.994, P = 0.032) and NCSS (hazard ratio: 4.058, P = 0.023) in the long term. Preoperative sarcopenia was an independent predictor of postoperative pneumonia following curative esophagectomy. Sarcopenia has been identified as a risk factor for reduced OS and NCSS. SMI measurement using BIA may be useful for preoperative risk assessment and informing treatment strategies.	esophagus
Real-world applications of postneoadjuvant stage I of the staging system for oesophageal squamous cell cancer: what is beyond a pathological complete response?	OBJECTIVES: The 8th edition of the American Joint Committee on Cancer classification system defines the postneoadjuvant pathological T0-2N0M0 (ypT0-2N0M0) stage as ypI for oesophageal cancer. This study was designed to explore the possible differences in survival among patients with yp stage I. METHODS: The records of patients with oesophageal squamous cell cancer staged ypI who underwent a radical oesophagectomy between July 2009 and July 2022 at the Sun Yat-sen University Cancer Center were reviewed. The survival differences were compared between ypT0, ypTis, ypT1a, ypT1b and ypT2. RESULTS: A total of 355 patients (65 deaths and 34 recurrences) were reviewed. Overall survival (OS) and disease-free survival (DFS) differed significantly between patients in the total population staged as ypT0-1a and ypT1b-2 [5-year OS (5-OS): 81.5% vs 70.2%, P = 0.043; 5-year DFS (5-DFS): 80.8% vs 71.9%, P = 0.016) in the neoadjuvant chemoradiotherapy (NCRT) group (5-OS: 82.0% vs 67.5%, P = 0.032; 5-DFS: 84.6% vs 71.2%, P = 0.027), but not in the neoadjuvant chemotherapy±I group (5-OS: 80.3% vs 72.9%, P = 0.34; 5-DFS: 66.5% vs 72.4%, P = 0.41). The OS and DFS of patients with ypT0 stage (pathological complete response) disease were similar to those of patients with ypTis-1a disease in the total population (P = 0.16 and 0.94) and the NCRT group (P = 0.40 and 0.57). Cox regression analysis revealed that ypT1b-2 was an independent prognostic factor for survival in the total population (hazard ratio = 1.760, 95% confidence interval = 1.056-2.933; P = 0.030). CONCLUSIONS: Patients with ypIa-new (ypT0-1aN0M0) disease had significantly better survival than those with ypIb-new (ypT1b-2N0M0) disease among patients who received NCRT. Patients with ypIa-new (pathological complete response and ypTis-1aN0M0) disease had similar survival data. Adjuvant immunotherapy might not be required for patients with ypTis-1aN0M0 stage disease.	esophagus
The antibody-drug conjugate SHR-A1904 for targeting CLDN18.2 in advanced gastric or gastroesophageal junction cancer: a phase 1 trial.	Claudin-18 isoform 2 (CLDN18.2), a tight junction protein expressed in non-malignant gastric epithelium and exposed on tumor cell surface during malignant transformation, is a promising therapeutic target for gastric and gastroesophageal junction (G/GEJ) cancers. SHR-A1904 is an antibody-drug conjugate comprising CLDN18.2-targeting monoclonal antibody, a DNA topoisomerase I inhibitor payload and a cleavable peptide-based linker. We conducted a first-in-human, three-stage, phase 1 study to evaluate SHR-A1904 in 95 previously treated patients with CLDN18.2-positive advanced G/GEJ cancer. In the dose-escalation stage (0.6-8.0 mg kg(-1)), dose-limiting toxicities were observed in two patients at 4.8 mg kg(-1) (grade 3 febrile neutropenia and grade 3 increased blood bilirubin) and in one patient at 6.0 mg kg(-1) (grade 3 gastric mucosal lesion). The maximum tolerated dose was not reached, and 6.0 mg kg(-1) and 8.0 mg kg(-1) were selected for pharmacokinetic and efficacy expansion. Treatment-emergent adverse events occurred in all 95 patients, most commonly anemia (72 (75.8%)), nausea (64 (67.4%)), hypoalbuminemia (61 (64.2%)) and decreased white blood cell count (56 (58.9%)). Additionally, 59 patients (62.1%) experienced drug-related grade 3 or higher adverse events. No treatment-related deaths were reported. Among response-evaluable patients, the confirmed objective response rate was 24.2% (95% confidence interval (CI), 11.1-42.3) at 6.0 mg kg(-1) and 25.0% (95% CI, 12.1-42.2) at 8.0 mg kg(-1). The median progression-free survival was 5.6 months (95% CI, 3.0-6.9) at 6.0 mg kg(-1) and 5.8 months (95% CI, 3.0-8.6) at 8.0 mg kg(-1). In conclusion, SHR-A1904 demonstrated a manageable safety profile and encouraging anti-tumor activity in patients with CLDN18.2-positive G/GEJ cancer, warranting further investigation. ClinicalTrials.gov identifier: NCT04877717 .	esophagus
National Analysis of Anastomotic Leak and Subsequent Failure to Rescue After Esophagectomy.	INTRODUCTION: Anastomotic leak is a major complication following esophagectomy, with persistently high incidence rates. A contemporary evaluation using a large national, generalizable database is warranted to identify the risk factors associated with leak development, trends in management, and contributors to subsequent failure to rescue (FTR). METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was used to identify patients who underwent an esophagectomy for cancer from 2016 to 2021. Predictors for anastomotic leak and FTR were identified using multivariable logistic regression analysis. RESULTS: 5582 patients met the inclusion criteria; 828 (14.8%) developed an anastomotic leak and 52 (6.2%) were unable to be rescued. Anastomotic leak rates have increased from 12% in 2016 to 16% in 2021 (P < 0.001). After adjusting for covariates; smoking (adjusted odds ratio [aOR] 1.28, P = 0.013), hypertension (aOR 1.33, P = 0.002), surgical conversion to open (aOR 1.44, P = 0.027), positive margins (aOR 1.39, P = 0.033), and three-field esophagectomy (aOR 1.46, P < 0.001) were independent predictors for developing an anastomotic leak. Among the patients with an anastomotic leak, age above 65 (aOR 2.9, P = 0.002), Black race (aOR 8.56, P < 0.001), and development of an additional postoperative complication (aOR 13.62, P < 0.001) were independent predictors for FTR. CONCLUSIONS: Patient characteristics such as active smoking or hypertension can inform preoperative optimization in an attempt to reduce morbidity and mortality. FTR after an anastomotic leak disproportionally affects older individuals, Black patients, and those who incur an additional postoperative complication. These patients require greater perioperative attention and prompt intervention if signs of a leak or an additional complication are identified.	esophagus
Developing a machine-learning model to enable treatment selection for neoadjuvant chemotherapy for esophageal cancer.	Although neoadjuvant chemotherapy with docetaxel + cisplatin + 5-fluorouracil (CF) has been the standard treatment for stage II and III esophageal cancers, it is associated with severe adverse events caused by docetaxel. Consequently, this study aimed to construct a prognostic system for CF regimens, especially for locally advanced esophageal cancers. Biopsy specimens from 82 patients treated with the CF regimen plus radical surgery were analyzed. Variants in 56 autophagy- and esophageal cancer-related genes were identified using targeted enrichment sequencing. Overall, 13 single-nucleotide variants, including 8 non-synonymous single-nucleotide variants, were identified as significantly associated with esophageal cancer recurrence (p < 0.05). Particularly, variants of ATG2A p.R478C and ULK2 splice-site also showed significant differences in recurrence-free and overall survival. Subsequently, machine learning was used to construct a model for predicting esophageal cancer recurrence based on 21 features, including eight patient characteristics. A Naive Bayes machine-learning model was shown to be highly reliable for predicting esophageal cancer recurrence with an accuracy of 0.88 and an area under the curve of 0.9. We believe that our results provide useful guidance in the selection of neoadjuvant adjuvant chemotherapy, including avoidance of docetaxel.	esophagus