crossing96/oncoscreening huggingface dataset:
Comprehensive Analyses Reveal Effects on Tumor Immune Infiltration and Immunotherapy Response of APOBEC Mutagenesis and Its Molecular Mechanisms in Esophageal Squamous Cell Carcinoma.	The apolipoprotein B mRNA editing enzyme catalytic polypeptide (APOBEC) mutagenesis is prevalent in esophageal squamous cell carcinoma (ESCC). However, the functional role of APOBEC mutagenesis has yet to be fully delineated. To address this, we collect matched multi-omics data of 169 ESCC patients and evaluate characteristics of immune infiltration using multiple bioinformatic approaches based on bulk and single-cell RNA sequencing (scRNA-seq) data and verified by functional assays. We find that APOBEC mutagenesis prolongs overall survival (OS) of ESCC patients. The reason for this outcome is probably due to high anti-tumor immune infiltration, immune checkpoints expression and immune related pathway enrichment, such as interferon (IFN) signaling, innate and adaptive immune system. The elevated AOBEC3A (A3A) activity paramountly contributes to the footprints of APOBEC mutagenesis and is first discovered to be transactivated by FOSL1. Mechanistically, upregulated A3A exacerbates cytosolic double-stranded DNA (dsDNA) accumulation, thus stimulating cGAS-STING pathway. Simultaneously, A3A is associated with immunotherapy response which is predicted by TIDE algorithm, validated in a clinical cohort and further confirmed in mouse models. These findings systematically elucidate the clinical relevance, immunological characteristics, prognostic value for immunotherapy and underlying mechanisms of APOBEC mutagenesis in ESCC, which demonstrate great potential in clinical utility to facilitate clinical decisions.	esophagus
RNF106 aggravates esophageal squamous cell carcinoma progression through LATS2/YAP axis.	Esophageal squamous cell carcinoma (ESCC) is one of the most lethal solid tumors in China, with the 5-year overall survival rate less than 20%. Although the carcinogenic process of ESCC is still not clear, recent studies using whole genomic profiling revealed that dysregulation of Hippo signaling pathway might play important roles in ESCC progression. The ubiquitin-like with PHD and RING finger domain 1 (RNF106) was a modifier of DNA methylation and histone ubiquitination. In this study, we evaluate the oncogenic function of RNF106 in ESCC both in vitro and in vivo. Wound healing and transwell data showed that RNF106 was required for ESCC cell migration and invasion. RNF106 depletion dramatically restrained Hippo signaling targeted gene expression. The bioinformatics analysis displayed that RNF106 was increased in ESCC tumor tissues and related with poor survival in ESCC patients. Mechanistic studies demonstrated that RNF106 was associated with LATS2 and facilitate LATS2 K48-linked ubiquitination and degradation, which subsequently inhibited YAP phosphorylation and promoted YAP oncogenic function in ESCC. Taken together, our study revealed a novel link between RNF106 and Hippo signaling in ESCC, suggesting that RNF106 could be a promising target for ESCC therapy.	esophagus
Muscular injury as an independent risk factor for esophageal stenosis after endoscopic submucosal dissection of esophageal squamous cell cancer.	BACKGROUND AND AIMS: Stenosis after esophageal endoscopic submucosal dissection (ESD) has a high incidence, and muscular injury is an important risk factor for esophageal stenosis. Hence, this study aimed to classify muscular injury degrees and investigate their association with postoperative stenosis. METHODS: This retrospective study included 1033 patients with esophageal mucosal lesions treated with ESD between August 2015 and March 2021. Demographic and clinical parameters were analyzed, and stenosis risk factors were identified using multivariate logistic regression. A novel muscular injury classification system was proposed and used to investigate the association between different muscular injury degrees and postoperative stenosis. Finally, a scoring system was established to predict muscular injury. RESULTS: Of 1033 patients, 118 (11.4%) had esophageal stenosis. The multivariate analysis demonstrated that the history of endoscopic esophageal treatment, circumferential range, and muscular injury were significant risk factors for esophageal stenosis. Patients with type II muscular injuries tended to develop complex stenosis (n = 13 [36.1%], P < .05), and type II muscular injuries were more likely to predispose patients to severe stenosis than type I (73.3% and 92.3%, respectively). The scoring system showed that patients with high scores (3-6) were more likely to have muscular injury. The score model presented good discriminatory power in the internal validation (area under the receiver-operating characteristic curve, .706; 95% confidence interval, .645-.767) and goodness-of-fit in the Hosmer-Lemeshow test (P = .865). CONCLUSIONS: Muscular injury was an independent risk factor for esophageal stenosis. The scoring system demonstrated good performance in predicting muscular injury during ESD.	esophagus
Radiotherapy-induced fibrosarcoma of the esophagus.	A patient presented with a 5-year history of slowly progressive dysphagia. He had moderately differentiated squamous cell carcinoma in the middle thoracic esophagus and underwent partial esophagogastrostomy 16 years prior. The patient with postoperative anastomotic stenoses was treated with radiotherapy at a total dose of 60 Gy after esophagectomy. Endoscopic submucosal dissection (ESD) was used to treat the recurrent tumor.Clinical specimens were obtained from the ESD and the tumor was pathologically confirmed to be fibrosarcoma.	esophagus
Identification and Prognostic Effect of Extramural Venous Invasion in Locally Advanced Esophageal Squamous Cell Carcinoma.	The role of extramural venous invasion (EMVI) in esophageal cancer is still unclear. This study aimed to identify EMVI and assess its impact on survival and recurrences in esophageal squamous cell carcinoma (ESCC). Retrospectively, we reviewed resection specimens of 147 locally advanced ESCC (pT3-T4aN0-3M0) patients who had a curative intended surgery alone at the Cancer Hospital of Shantou University from March 2009 to December 2013. After confirming pT≥3 in hematoxylin-eosin tumor slides, EMVI was evaluated by Verhoeff and Caldesmon staining. The impact of EMVI with other clinicopathological characteristics and survival were analyzed using the χ 2 test, Cox regression, and Kaplan-Meier method. EMVI was present in 30.6% (45/147) of the P ≥T3 ESCCs and associated with lymph-vascular invasion and poor differentiation grade ( P <0.05). Disease-free survival and overall survival in patients with EMVI-absent tumors were about 2.0 times longer than in those with EMVI-present tumors. In pN0 patients, EMVI-presence was associated with poor overall survival (HR 4.829, 95% CI 1.434-16.26, P =0.003) and Disease-free Survival (HR 4.026, 95% CI 0.685-23.32, P =0.018). In pN1-3 patients, EMVI had no additional effect on survival. Conclusions EMVI has an independent adverse prognostic effect on survival in ESCC patients after surgery alone. EMVI should be included in pathology reports as it might contribute to identify high-risk patients for potential additional treatment.	esophagus
Nasogastric tube feeding improves nutritional status and physical state in esophageal cancer patients during chemoradiotherapy: a retrospective study.	OBJECTIVE: To compare the complication rates, nutritional status, and physical state between esophageal cancer (EC) patients managed by nasogastric tube (NGT) feeding versus those managed by oral nutritional supplementation (ONS) during chemoradiotherapy. METHODS: EC patients undergoing chemoradiotherapy managed by nonintravenous nutritional support in our institute were retrospectively recruited and divided into an NGT group and an ONS group based on the nutritional support method. The main outcomes, including complications, nutritional status, and physical state, were compared between groups. RESULTS: The baseline characteristics of EC patients were comparable. There were no significant differences in the incidence of treatment interruption (13.04% vs. 14.71%, P = 0.82), death (2.17% vs. 0.00%, P = 0.84), or esophageal fistula (2.17% vs. 1.47%, P = 1.00) between the NGT group and ONS group. Body weight loss and decrease in albumin level were significantly lower in the NGT group than in the ONS group (both P < 0.05). EC patients in the NGT group had significantly lower Nutritional Risk Screening 2002 (NRS2002) and Patient-Generated Subjective Global Assessment (PG-SGA) scores and significantly higher Karnofsky Performance Status (KPS) scores than patients in the ONS group (all P < 0.05). The rates of grade > 2 esophagitis (10.00% vs. 27.59%, P = 0.03) and grade > 2 bone marrow suppression (10.00% vs. 32.76%, P = 0.01) were significantly lower in the NGT group than in the ONS group. There were no significant differences in the incidence of infection and upper gastrointestinal disorders or therapeutic efficacy between groups (all P > 0.05). CONCLUSIONS: EN through NGT feeding leads to significantly better nutritional status and physical state in EC patients during chemoradiotherapy than EN via ONS. NGT may also prevent myelosuppression and esophagitis..	esophagus
Plasma miR-1254 as a predictive biomarker of chemosensitivity and a target of nucleic acid therapy in esophageal cancer.	This study investigated novel tumor suppressor microRNAs (miRNAs) that decrease in plasma and predict chemosensitivity to neoadjuvant chemotherapy (NAC) for esophageal squamous cell carcinoma (ESCC) and revealed their usefulness as novel therapeutic agents. We selected four miRNA candidates (miR-323, 345, 409, and 1254) based on the microRNA microarray comparing pre-treatment plasma levels in ESCC patients with high and low histopathological responses to NAC and an NCBI database review. Among these miRNA candidates, miR-1254 was more highly elevated in pre-treatment plasma of ESCC patients with a high histopathological response than in those with a low histopathological response (P = 0.0021, area under the receiver-operating characteristic curve 0.7621). High plasma miR-1254 levels tended to correlate with the absence of venous invasion (P = 0.0710) and were an independent factor predicting a higher response to chemotherapy (P = 0.0022, odds ratio 7.86) and better prognosis (P = 0.0235, hazard ratio 0.23). Overexpressing miR-1254 in ESCC cells significantly enhanced chemosensitivity to cisplatin through the transcriptional regulation of ABCC1 in vitro. Moreover, increased plasma miR-1254 levels by subcutaneous injection significantly improved responses to cisplatin in mice. Plasma miR-1254 might be a useful biomarker for predicting responses to NAC, and the restoration of plasma miR-1254 levels might improve chemosensitivity in ESCC.	esophagus
Downregulation of miR-100-5p in cancer-associated fibroblast-derived exosomes facilitates lymphangiogenesis in esophageal squamous cell carcinoma.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC), an aggressive gastrointestinal tumor, often has high early lymphatic metastatic potential. Cancer-associated fibroblasts (CAFs) are primary components in tumor microenvironment (TME), and the impact of CAFs and its derived exosomes on lymphangiogenesis remains elusive. MATERIALS AND METHODS: CAFs and the microlymphatic vessel density (MLVD) in ESCC was examined. Exosomes were extracted from primary normal fibroblast (NFs) and CAFs. Subsequently, tumor-associated lymphatic endothelial cells (TLECs) were treated with these exosomes, and the effect on their biological behavior was examined. miR-100-5p was selected as the target miRNA, and its effect on TLECs was examined. The target of miR-100-5p was predicted and confirmed. Subsequently, IGF1R, PI3K, AKT, and p-AKT expression in TLECs and tumors treated with exosomes and miR-100-5p were examined. RESULTS: A large number of CAFs and microlymphatic vessels were present in ESCC, leading to a poor prognosis. CAF-derived exosomes promoted proliferation, migration, invasion, and tube formation in TLECs. Further, they also enhanced lymphangiogenesis in ESCC xenografts. miR-100-5p levels were significantly lower in CAF-derived exosomes than in NF-derived exosomes. miR-100-5p inhibited proliferation, migration, invasion, and tube formation in TLECs. Further, miR-100-5p inhibited lymphangiogenesis in ESCC xenografts. Mechanistic studies revealed that this inhibition was mediated by the miR-100-5p-induced inhibition of IGF1R/PI3K/AKT axis. CONCLUSION: Taken together, our study demonstrates that CAF-derived exosomes with decreased miR-100-5p levels exhibit pro-lymphangiogenesis capacity, suggesting a possibility of targeting IGF1R/PI3K/AKT axis as a strategy to inhibit lymphatic metastasis in ESCC.	esophagus
Maximum phonation time: an independent predictor of late-onset pneumonia after esophageal cancer surgery.	Dysphagia after esophagectomy is a major risk factor for aspiration pneumonia, thus preoperative assessment of swallowing function is important. The maximum phonation time (MPT) is a simple indicator of phonatory function and also correlates with muscle strength associated with swallowing. This study aimed to determine whether preoperative MPT can predict postoperative aspiration pneumonia. The study included 409 consecutive patients who underwent esophagectomy for esophageal cancer between 2017 and 2021. Pneumonia detected by routine computed tomography on postoperative days 5-6 was defined as early-onset pneumonia, and pneumonia that developed later (most often aspiration pneumonia) was defined as late-onset pneumonia. The correlation between late-onset pneumonia and preoperative MPT was investigated. Patients were classified into short MPT (<15 seconds for males and <10 seconds for females, n = 156) and normal MPT groups (≥15 seconds for males and ≥10 seconds for females, n = 253). The short MPT group was significantly older, had a lower serum albumin level and vital capacity, and had a significantly higher incidence of late-onset pneumonia (18.6 vs. 6.7%, P < 0.001). Multivariate analysis showed that short MPT was an independent risk factor for late-onset pneumonia (odds ratio: 2.26, P = 0.026). The incidence of late-onset pneumonia was significantly higher in the short MPT group (15.6 vs. 4.7%, P = 0.004), even after propensity score matching adjusted for clinical characteristics. MPT is a useful predictor for late-onset pneumonia after esophagectomy.	esophagus
Elevated APE1 Dysregulates Homologous Recombination and Cell Cycle Driving Genomic Evolution, Tumorigenesis, and Chemoresistance in Esophageal Adenocarcinoma.	BACKGROUND & AIMS: The purpose of this study was to identify drivers of genomic evolution in esophageal adenocarcinoma (EAC) and other solid tumors. METHODS: An integrated genomics strategy was used to identify deoxyribonucleases correlating with genomic instability (as assessed from total copy number events in each patient) in 6 cancers. Apurinic/apyrimidinic nuclease 1 (APE1), identified as the top gene in functional screens, was either suppressed in cancer cell lines or overexpressed in normal esophageal cells and the impact on genome stability and growth was monitored in vitro and in vivo. The impact on DNA and chromosomal instability was monitored using multiple approaches, including investigation of micronuclei, acquisition of single nucleotide polymorphisms, whole genome sequencing, and/or multicolor fluorescence in situ hybridization. RESULTS: Expression of 4 deoxyribonucleases correlated with genomic instability in 6 human cancers. Functional screens of these genes identified APE1 as the top candidate for further evaluation. APE1 suppression in EAC, breast, lung, and prostate cancer cell lines caused cell cycle arrest; impaired growth and increased cytotoxicity of cisplatin in all cell lines and types and in a mouse model of EAC; and inhibition of homologous recombination and spontaneous and chemotherapy-induced genomic instability. APE1 overexpression in normal cells caused a massive chromosomal instability, leading to their oncogenic transformation. Evaluation of these cells by means of whole genome sequencing demonstrated the acquisition of changes throughout the genome and identified homologous recombination as the top mutational process. CONCLUSIONS: Elevated APE1 dysregulates homologous recombination and cell cycle, contributing to genomic instability, tumorigenesis, and chemoresistance, and its inhibitors have the potential to target these processes in EAC and possibly other cancers.	esophagus
Role of miR-424 in the carcinogenesis.	Recent studies have revealed the impact of microRNAs (miRNAs) in the carcinogenic process. miR-424 is a miRNA whose role in this process is being to be identified. Experiments in the ovarian cancer, cervical cancer, hepatocellular carcinoma, neuroblastoma, breast cancer, osteosarcoma, intrahepatic cholangiocarcinoma, prostate cancer, endometrial cancer, non-small cell lung cancer, hemangioma and gastric cancer have reported down-regulation of miR-424. On the other hand, this miRNA has been found to be up-regulated in melanoma, laryngeal and esophageal squamous cell carcinomas, glioma, multiple myeloma and thyroid cancer. Expression of this miRNA is regulated by methylation status of its promoter. Besides, LINC00641, CCAT2, PVT1, LIN00657, LINC00511 and NNT-AS1 are among lncRNAs that act as molecular sponges for miR-424, thus regulating its expression. Moreover, several members of SNHG family of lncRNAs have been found to regulate expression of miR-424. This miRNA is also involved in the regulation of E2F transcription factors. The current review aims at summarization of the role of miR-424 in the process of cancer evolution and its impact on clinical outcome of patients in order to find appropriate markers for malignancies.	esophagus
Computed tomography-based radiomic analysis for predicting pathological response and prognosis after neoadjuvant chemotherapy in patients with locally advanced esophageal cancer.	PURPOSE: Accurate prediction of prognosis and pathological response to neoadjuvant chemotherapy (NAC) is crucial for optimizing treatment strategies for patients with locally advanced esophageal cancer (LA-EC). This study aimed to investigate the use of radiomics for pretreatment CT in predicting the pathological response of patients with LA-EC to NAC. METHODS: Overall, 144 patients (145 lesions) with LA-EC who underwent pretreatment contrast-enhanced CT and then received NAC followed by surgery with pathological tumor regression grade (TRG) analysis were enrolled. The obtained dataset was randomly divided into training and validation cohorts using fivefold cross-validation. CT-based radiomic features were extracted followed by the feature selection process using the variance threshold, SelectKBest, and least absolute shrinkage and selection operator methods. The radiomic model was constructed using six machine learning classifiers, and predictive performance was evaluated using ROC curve analysis in the training and validation cohorts. RESULTS: All patients were divided into responders (n = 40, 28%) and non-responders (n = 104, 72%) based on the TRG results and a statistically significant split by overall survival analysis (0.899 [0.754-0.961] vs. 0.630 [0.510-0.729], respectively). There were no significant differences between responders and non-responders in terms of age, sex, tumor size, tumor location, or histopathology. The mean AUC of fivefold in the validation cohort was 0.720 (confidence interval [CI]: 0.594-0.982), and the best AUC of the radiomic model using logistic regression to predict the non-responders was 0.815 (CI: 0.626-1.000, sensitivity 0.620, specificity 0.860). CONCLUSION: A radiomic model derived from contrast-enhanced CT may help stratify chemotherapy effect prediction and improve clinical decision-making.	esophagus
Tracheoesophageal fistula closure after staged dose-escalated radiotherapy for esophageal squamous cell carcinoma: a case report.	An esophageal fistula can be caused by an esophageal tumor as well as the surgery, radiotherapy (RT), or chemoradiotherapy used to treat the tumor. The most dangerous complications are massive hemoptysis and asphyxia. This report describes a 58-year-old man with a >1-month history of dysphagia and hemoptysis. Contrast-enhanced computed tomography revealed a tumor in the upper esophagus and a tracheoesophageal fistula. Esophagography revealed a large lesion measuring approximately 8 cm in length. Esophagogastroduodenoscopy showed an ulcerated tumor with raised margins originating 22 cm from the incisors, and histologic examination of a biopsy specimen indicated squamous cell carcinoma. The tumor was finally classified as stage IVA (T4bN0M0) esophageal squamous cell carcinoma. Massive hemoptysis occurred after the patient was admitted to the hospital. Therefore, we applied staged dose-escalated RT in three stages (6.0 Gy in 5 fractions, 7.5 Gy in 5 fractions, and 46.8 Gy in 26 fractions) to decrease the rate of tumor shrinkage brought on by RT and give the normal tissue enough time to close the fistula. Finally, the hemoptysis resolved and the patient's symptoms were significantly improved. Contrast-enhanced chest computed tomography revealed shrinkage of the tumor. In conclusion, staged dose-escalated RT can be applied for esophageal fistula closure.	esophagus
Comparison between radical surgery and chemoradiotherapy in patients with cervical esophageal cancer: a propensity score matched analysis.	BACKGROUND: The prognostic value of radical surgery (RS) and chemoradiotherapy (CRT) for cervical esophageal cancer (CEC) was estimated using the Surveillance, Epidemiology and End Results (SEER) database after 1:1 propensity score matching (PSM). METHODS: This retrospective study used SEER data of CEC patients between 2004 and 2015. The prognostic effects on cancer-specific survival (CSS) were evaluated using multivariate cox regression analysis following radical surgery or CRT before and after PSM. The subgroup analysis of CSS is carried out according to T stages. RESULTS: A total of 440 patients met the eligibility criteria. Three hundred and fifty-six(80.9%)patients underwent chemoradiotherapy, and eighty-four (19.1%) patients underwent radical surgery. There were significant differences between patients of radical surgery and CRT groups with regard to the tumor grade, histology and N stage. After PSM, 80 matched pairs (A total of 160 patients) were selected. Multivariable cox regression analysis revealed no difference in the CSS of patients that underwent either radical surgery or CRT before [hazard ratio (HR): 0.955, 95% CI: 0.704-1.295, P = 0.766] and after PSM (HR: 0.767, 95% CI: 0.512-1.149, P = 0.198). Subgroup analysis revealed no significant difference in CSS between patients with radical surgery and CRT groups for all T stages (T 1-4, all P > 0.05). CONCLUSIONS: This analysis revealed that the prognostic outcomes in patients with cervical esophageal cancer were comparable between radical surgery and CRT.	esophagus