crossing96/oncoscreening huggingface dataset:
SETD7-mediated H3K4me1 activates ALDH1A3 to drive ferroptosis resistance in esophageal squamous cell carcinoma.	SET domain-containing 7 (SETD7, also known as KMT7 or SET7/9), a histone lysine methyltransferase (HKMT) responsible for catalyzing histone H3 lysine 4 monomethylation (H3K4me1), has emerged as a key regulator in multiple cancers. However, the biological functions and epigenetic regulatory mechanisms of SETD7 in esophageal squamous cell carcinoma (ESCC) remain unclear. Our study found that SETD7 expression is significantly upregulated in ESCC tissues and positively correlates with clinical staging. Functional analyses revealed that SETD7 promotes ESCC cell proliferation and migration in vitro, while accelerating tumor growth in vivo. Additionally, SETD7 knockdown increased ESCC cell sensitivity to ferroptosis induction, indicating its dual functionality in tumorigenesis and ferroptosis resistance. Cleavage Under Targets and Tagmentation (CUT&Tag) sequencing analysis systematically mapped H3K4me1 modifications in ESCC cells, identifying ALDH1A3 (aldehyde dehydrogenase 1 family member A3) as a key downstream target. Mechanistically, SETD7-mediated H3K4me1 deposition at the ALDH1A3 promoter drives transcriptional activation, increasing the level of reduced coenzyme Q10 (CoQ10H₂) and inhibiting lipid peroxidation. This study reveals a novel epigenetic-metabolic axis (SETD7-H3K4me1-ALDH1A3/NADH/CoQ10H₂) that regulates ESCC progression and ferroptosis sensitivity, which highlights the clinical translational value of SETD7 in ESCC prognosis assessment and therapeutic development. Schematic diagram illustrating the mechanism by which SETD7 accelerates ESCC progression through enhancing ferroptosis resistance. Created with BioRender.	esophagus
A prediction score model of difficult endoscopic submucosal dissection for early esophageal cancer and precancerous lesions.	BACKGROUND: To establish a prediction model to triage difficult esophageal endoscopic submucosal dissection (ESD) in order to reduce complications. METHODS: This retrospective study enrolled 742 patients who underwent ESD for early esophageal cancer and precancerous lesions. Difficult ESDs were defined as those meeting any of the following criteria: (1) long procedure time (≥ 90 min), (2) occurrence of intraoperative adverse events (muscularis propria injury, perforation, and massive hemorrhage), or (3) piecemeal resection. Logistic regression analysis was performed to identify the predictors of technical difficulty. Then we developed a score prediction model according to the Framingham system for the first time and presented a convenient table containing the risk probability for each patient. In addition, the score model was validated in the validation cohort. RESULTS: The risk factors for difficult ESDs were as follows: lesion total length 4-6 cm (1 point), 7-9 cm (2 points) or ≥10 cm (3 points); lesion ≥ 2/3 circumference (2 points); preoperative invasion depth extending to submucosa (2 points). Areas under ROC curves for the score model in the derivation and validation sets were 0.768 (95% CI, 0.726-0.811) and 0.719 (95% CI, 0.646-0.793), respectively. In addition, the percentage of difficult ESDs in easy (score = 0), intermediate (score = 1-2), difficult (score = 3-4), and very difficult (score ≥5) categories were 14.8%, 36.1%, 62.6%, and 87.5% in the derivation cohort and 14.8%, 33.7%, 56.3%, and 68.8% in the internal validation cohort. CONCLUSIONS: We successfully established a prediction model to assess the difficulty of esophageal ESD and it can provide a scientific basis for clinical management to reduce complications.	esophagus
Oral microbiota analysis of tongue coating in patients with esophageal adenocarcinoma.	The incidence of esophageal adenocarcinoma (EAC) has been steadily rising in China, emphasizing the need for effective strategies in primary prevention and early detection. Emerging evidence suggests that tongue coating microbiota may play a significant role in gastrointestinal diseases. However, the alterations in tongue coating microbiota and associated metabolic pathways in Chinese EAC patients remain poorly understood. This case-control study analyzed tongue coating microbiota samples from 28 EAC patients and 28 age- and sex-matched control subjects. Microbiota composition and predicted metabolic functions were assessed using PICRUSt2. Alpha diversity was measured using the Shannon and Chao1 indices, and microbial taxa were compared between groups using the Wilcoxon signed-rank test. The Shannon index was significantly higher in the EAC group (P = .033), suggesting greater microbial diversity, while no significant difference was found in the Chao1 index (P = .50). The EAC group exhibited significant enrichment of Porphyromonas and Tannerella, while Rothia was significantly reduced. Predicted metabolic pathways, including pyrimidine metabolism, amino acid metabolism, and carbon metabolism, showed notable differences between the groups. This exploratory study highlights distinct alterations in tongue coating microbiota and metabolic functions in EAC patients, offering potential insights for the development of noninvasive diagnostic approaches for EAC.	esophagus
Validity of using plastic bags to wrap the esophagus after the thoracic procedure during radical esophageal cancer surgery.	During surgery for thoracic esophageal cancer, the resected esophagus remains in the thoracic cavity, allowing fluid to leak from the specimen. If this fluid contains cancer cells, they may spread throughout the cavity. However, the presence and prognostic impact of free cancer cells in leaked fluid from the esophagus (LF-E) remain unclear. We conducted a prospective cohort study of 96 patients with thoracic esophageal cancer who underwent radical subtotal esophagectomy. After the thoracic procedure, the esophagus was placed in a bag and removed following the abdominal and cervical procedures. Fluid collected from the bag, combined with saline used to rinse the specimen, was defined as LF-E and examined cytologically. We evaluated the clinicopathological characteristics and prognosis of LF-E-positive (LF-E [+]) patients. LF-E (+) was observed in 5 of 96 patients (5.2%), all of whom had pT3 or higher squamous cell carcinoma with nodal metastasis and vascular invasion. Among the 44 patients with pT3-4a disease, those in the LF-E (+) group had significantly poorer regression-free survival (RFS) (P < 0.001) and overall survival (OS) (P < 0.001) than those in the LF-E-negative group. Multivariate Cox regression analysis identified LF-E positivity as an independent prognostic factor for RFS (hazard ratio [HR]: 4.57, 95% confidence interval [CI]: 1.21-16.2, P = 0.026) and OS (HR: 11.9, 95% CI: 2.04-69.1, P = 0.008). The presence of free cancer cells in LF-E indicated a poor prognosis in patients with pT3 or higher esophageal cancer. LF-E positivity may serve as a new prognostic biomarker.	esophagus
Hypermethylated USP44 deubiquitinates SENP2: a critical mechanism in esophageal cancer progression and a new target for intervention.	BACKGROUND: Ubiquitin-specific proteases (USPs) play a critical role in the development of various cancers. The study aimed to elucidated the pathogenic molecular mechanisms and analyze its clinical significance in esophageal squamous cell carcinoma (ESCC). METHODS: Pyrosequencing, RT-qPCR and Western blot were used to detect the promoter DNA methylation level and expression of USP44 in ESCC tissues and cell lines, and the significance of USP44/SENP2 in the progression of ESCC was evaluated by in vitro and in vivo experiments. The regulatory mechanism of USP44 on SENP2 was explored by liquid chromatography-mass spectrometry, co-immunoprecipitation (Co-IP) combined with cycloheximide (CHX) tracking assay and ubiquitination analysis. Finally, 182 ESCC tissues were stained with immunohistochemistry (IHC), and the correlation between USP44 and prognosis was evaluated by Kaplan-Meier survival analysis, Cox regression and Nomogram model. RESULTS: In ESCC tumor tissues and cell lines, USP44 is frequently hypermethylated and downregulated. Overexpression of USP44 significantly inhibits ESCC cell invasion and metastasis both in vitro and in vivo. Mechanistically, USP44 interacts with and stabilizes ubiquitin-like modifier (SUMO)-specific peptidase 2 (SENP2) through deubiquitination, thereby inhibiting the progression of ESCC. Knockdown of SENP2 reduced the inhibitory effect of USP44 on ESCC cell migration and invasion. Clinically, low expression of USP44 indicates poor prognosis and is an independent prognostic factor in ESCC patients, as evidenced by Kaplan-Meier curve and cox regression analysis (HR = 0.345, 95% CI 0.227-0.524, p < 0.001). We established a nomogram model with robust predictive power for the 1-, 3-, and 5-year survival of ESCC patients (AUC = 0.849). CONCLUSION: USP44-SENP2 axis is a pivotal factor in the progression of ESCC, and provides potential therapeutic targets for ESCC patients.	esophagus
Brief preoperative frailty predicts postoperative adverse outcomes in older patients with radical esophageal cancer surgery.	BACKGROUND: Frailty is increasingly becoming a powerful prognostic factor for cancer patients. The purpose of this study was to investigate the prognostic effect of 5-modified frailty index (mFI-5) on adverse outcomes after surgery in older patients with esophageal cancer over 65 years of age. METHODS: Patients over 65 years old who underwent esophagectomy between January 1, 2014 and January 31, 2017 were included in the study analysis. The mFI-5 variables include hypertension, type Ⅱ diabetes, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), and independent functional status. Patients were divided into 3 groups: robust group (mFI-5, 0), prefrail group (mFI-5, 1) and frail group (mFI-5, 2 ~ 5). Primary outcome was 30-day mortality. Secondary outcomes were postoperative delirium and pneumonia. Logistic regression analyzes and COX analyzes were used to identify independent risk factors for outcomes. The receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to evaluate the predictive efficacy and clinical net benefit of different variables in predicting outcomes. Delong test was used to compare and discern the effectiveness of two ROC curves in a classification setting. RESULTS: A total of 699 patients were included in this retrospective cohort study, of which 342 (48.93%) in the robust group, 184 (26.32%) patients in the prefrail group, and 173 (24.75%) patients were in the frail group. Frail patients identified by mFI-5 had the highest incidence of postoperative 30-day mortality (frailty: 5.8% vs. prefrail: 1.6% vs. robust: 1.2%), delirium (22.5% vs. 14.7% vs. 2.9%, P < 0.001) and pneumonia (13.3% vs. 9.8% vs. 3.8%, P < 0.05). Multivariate stepwise regression analysis found that frailty was associated with a significantly increased risk of postoperative 30-day mortality [adjusted Odds Ratio (aOR) = 14.30, 95%CI: 4.87-42.03, P < 0.001], delirium (aOR = 6.82, 95%CI: 3.12-14.89, P < 0.001), and pneumonia (aOR = 4.12, 95%CI: 2.52-6.72, P < 0.001). mFI-5 combined with Age and ASA classification had the highest predictive value in predicting postoperative adverse outcomes in older patients with esophageal cancer [30-day mortality area under curve (AUC): 0.84; delirium AUC: 0.78, and pneumonia AUC: 0.67]. CONCLUSIONS: The 5-modified frailty index is a convenient and effective tool to predict postoperative 30-day mortality, delirium and pneumonia in older patients over 65 years old undergoing esophagectomy. The mFI-5 could guide clinical decision-making and become a highly promising prognostic scale for risk stratification of esophageal cancer older patients.	esophagus
Survival outcomes of the use of adjuvant chemotherapy in resected esophagus cancer after neoadjuvant chemoradiotherapy.	INTRODUCTION: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the standard treatment for esophageal cancer, but the role of adjuvant chemotherapy remains unclear. This study investigates the survival benefits of adjuvant chemotherapy in patients undergoing nCRT and surgery. METHODS: A total of 1212 esophageal cancer patients who underwent nCRT and surgery, with or without adjuvant chemotherapy, between January 2008 and December 2018 were identified from the Taiwan Cancer Registry and National Health Insurance Research Database. The Cox regression analysis was utilized to evaluate the impact of adjuvant chemotherapy on 5-year mortality rates. RESULTS: Of the 1212 patients, 276 (22.8 %) received adjuvant chemotherapy, while 936 (77.2 %) did not. The most used chemotherapy regimens were cisplatin and 5-FU. Younger age (<60 years), advanced pathological tumor stage (ypT3-4), and nodal involvement (ypN1-3) were significantly associated with the use of adjuvant chemotherapy. Survival analysis showed that patients receiving adjuvant chemotherapy had worse survival outcomes in comparison to those who did not, 99/276 (35.87 %) and 417/936 (44.55 %), but without statistical significance after multivariable Cox regression analysis (adjusted hazard ratio [aHR], 1.11; 95 % Confidence Interval [CI], 0.93-1.33). Stratified analysis of 5-year mortality also failed to demonstrate a protective effect of adjuvant chemotherapy, even in patients with advanced clinical T or N classification. CONCLUSIONS: Adjuvant chemotherapy provides limited survival benefit for esophageal cancer patients following nCRT and surgery. Alternative strategies, such as immune checkpoint inhibitors or their combination with chemotherapy, should be explored.	esophagus
Association of energy expenditure with body composition and nutritional intake in male patients with esophageal and head and neck cancer.	Objective;In order to maintain a patient's adequate nutritional status, it is important to accurately assess energy expenditure and to provide nutritional administration commensurate with that expenditure. In this study, we have assessed the resting energy expenditures (REE) in patients with esophageal and head and neck cancer, and association between REE, metabolites, nutritional intake, and body composition. Methods;Patients included in the study had to be diagnosed with esophageal and head and neck cancer, and hospitalized and receiving chemotherapy. REE was measured using indirect calorimetry with a mask and calculated using 3 different equations. Result;Patients with esophageal and head and neck cancer (67.1±8.5 years old, n=52, all patients were male) were enrolled. The average of REE measured by indirect calorimetry were 22.1kcal/kg/day. REE was positively correlated with muscle mass, body cell mass, and lean body mass. REE was higher in group with oral intake of more than 72%. Blood levels of lactate, pyruvate, and amino acids were higher in cancer patients with esophageal and head and neck cancer compared to healthy subjects. Conclusion:REE measured by indirect calorimetry correlated with the estimated BEE. There was an association between energy expenditure and muscle mass and nutritional intake. J. Med. Invest. 72 : 252-259, August, 2025.	esophagus
Single-cell transcriptomic analysis reveals epithelial and microenvironmental heterogeneity in small cell carcinoma of the esophagus.	BACKGROUND: Small cell carcinoma of the esophagus (SCCE) is a rare and highly aggressive malignancy with limited therapeutic options and poor prognosis. The paucity of clinical specimens and lack of established experimental models have hindered a comprehensive understanding of its cellular heterogeneity and tumor microenvironment. METHODS: We performed single-cell RNA sequencing on SCCE samples, and integrated them with publicly available scRNA-seq datasets from esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and adjacent normal tissues (NT) from ESCC and EAC cases. An integrative transcriptomic analysis was conducted to identify cell types, infer malignant states, reconstruct differentiation trajectories, evaluate immune landscapes, and investigate fibroblast subtypes and cell-cell communication networks. RESULTS: SCCE tumors were characterized by a predominance of malignant epithelial cells and exhibited a profoundly immunosuppressed phenotype, with reduced immune infiltration and widespread downregulation of immune checkpoint genes. Malignant epithelial cells showed pronounced chromosomal instability and were classified into three transcriptionally distinct subtypes with divergent differentiation trajectories. The tumor microenvironment featured a complex stromal compartment, with enrichment of extracellular matrix fibroblasts (eCAFs) characterized by elevated ELF3 regulatory activity, and collagen-driven signaling predominantly mediated by inflammatory CAFs (iCAFs). SCCE also showed the most intricate cell-cell communication network among esophageal cancer subtypes. CONCLUSION: Our single-cell atlas offers a detailed view of the cellular heterogeneity and microenvironmental complexity of SCCE, highlighting its distinct tumor architecture, immune exclusion, and stromal reprogramming. These findings provide a valuable resource for understanding SCCE biology and form a basis for future mechanistic and exploratory biological investigations.	esophagus
Intratumoral regulatory T cells are associated with treatment response to neoadjuvant chemotherapy and prognosis in gastroesophageal adenocarcinoma.	Gastroesophageal junction (GEJ) adenocarcinoma is an increasingly common cancer with complex biology and poor prognosis. The treatment strategy for locally advanced tumors involves multimodal treatment with perioperative chemotherapy. However, survival rates remain low, especially for advanced disease. Here, formalin-fixed paraffin-embedded tumor sections from 72 patients with GEJ I and II adenocarcinoma who underwent primary resection or perioperative standard-of-care FLOT treatment were analyzed for their intratumoral T cell composition using multiplex immunohistochemistry. The proportions of T cells and their influence on survival were evaluated using Mann-Whitney U and log rank analyses. A comparison of short- and long-term survivors revealed significant differences in the infiltration of regulatory T cells (Tregs). Tumors after neoadjuvant FLOT treatment presented increased proportions of CD8(+) T cells with reduced Granzyme B expression, indicating an altered immune response. Overall survival analysis revealed that high infiltration of Tregs was associated with poor survival. Notably, responders to FLOT therapy had a greater T cell frequency and improved survival, whereas nonresponders presented higher levels of Tregs and CD8(+) T cells expressing TIM-3. Overall, GEJ cancer patients had increased CD8(+) T cells after neoadjuvant chemotherapy with FLOT, and Tregs were associated with treatment response and reduced survival.	esophagus
The Efficacy and Safety of Endostatin Combined with Definitive Chemoradiotherapy for Unresectable Esophageal Squamous Cell Carcinoma: A Retrospective Analysis.	BACKGROUND/AIMS: This retrospective analysis examined the efficacy and safety of combined endostatin and definite chemoradiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma. METHODS: The current study was a retrospective analysis of esophageal squamous cell carcinoma patients treated with endostatin combined with definitive chemoradiotherapy. The patients received induction chemotherapy or concurrent chemotherapy. The endostatin dose was 30 mg/d from days one to five of each induction cycle. During concurrent therapy, the endostatin dose was 30 mg/d concomitant with radiotherapy at 60-68 Gy delivered in 2.0-2.2 Gy/d fractions. RESULTS: The objective response and disease control rates were 82.76% and 84.48%, respectively. The one-year, two-year, and three-year overall survival rates were 91.83%, 86.43%, and 73.86%, respectively. The one-year, two-year, and three-year progress-free survival rates were 74.09%, 62.16%, and 61.95%, respectively. The most common grade 3 and 4 adverse events were esophagitis (31.03%), anemia (12.07%), pneumonia (12.07%), leukopenia (10.34%), neutropenia (8.62%) and thrombocytopenia (8.62%). CONCLUSIONS: A combination of endostatin with definite chemoradiotherapy in patients with unresectable esophageal squamous cell carcinoma achieved high response rates, progress-free survival rates, and overall survival rates. The toxicity was acceptable. Nevertheless, additional prospective randomized controlled clinical trials will be needed to confirm the superiority of this treatment strategy.	esophagus
Biocompatible hydrogel co-delivering salvigenin and iridium (III) complex overcomes cancer stemness and cisplatin resistance in esophageal squamous cell carcinoma.	Esophageal squamous cell carcinoma (ESCC) remains a challenging disease due to its aggressive nature and resistance to conventional treatments. This study presents an innovative injectable hydrogel (Ir-SAL@SA-CS) combining an iridium(III) complex with the natural flavonoid Salvigenin in a sodium alginate-chitosan matrix, designed to enhance therapeutic outcomes and reduce toxicity. In vitro experiments on TE6 and KYSE150 esophageal cancer cell lines demonstrated that this dual-drug hydrogel significantly reduced cell viability, with IC₅₀ values of approximately 31 µg/mL and 16 µg/mL, respectively, which is better than that of cisplatin. Normal esophageal cells (Het-1A) remained over 60 % viable at higher concentrations, indicating strong biocompatibility. Mechanistic studies revealed that the Ir-SAL@SA-CS induces mitochondrial dysfunction and elevates reactive oxygen species, triggering apoptosis in cancer cells. In vivo, intratumoral administration in a mouse xenograft model nearly eradicated tumor growth without affecting body weight or the function of vital organs. Serum markers and histopathology confirmed minimal systemic toxicity. RT-PCR results showed marked downregulation of stemness-related genes (Nanog, SOX2, OCT4), suggesting effective targeting of cancer stem cells. Compared to cisplatin, Ir-SAL@SA-CS demonstrated enhanced antitumor activity and a safer profile. These findings support the potential of combining metal complexes and natural agents within injectable hydrogels as a promising strategy for treating esophageal cancer.	esophagus
Perioperative outcomes of neoadjuvant chemotherapy plus camrelizumab versus neoadjuvant chemotherapy plus tislelizumab for locally advanced esophageal squamous cell cancer: a real-world retrospective study.	BACKGROUND: While neoadjuvant chemoimmunotherapy shows promise for locally advanced esophageal squamous cell carcinoma (ESCC), optimal regimen selection remains challenging. This study compares perioperative outcomes between camrelizumab- and tislelizumab-based neoadjuvant chemoimmunotherapy in ESCC. METHODS: We conducted a retrospective analysis of 209 clinical stage II-IVA ESCC patients treated at Hebei Medical University Fourth Hospital (October 2020-December 2023) who underwent neoadjuvant chemoimmunotherapy (camrelizumab, n=119; tislelizumab, n=90) followed by esophagectomy. RESULTS: Comparable pathological responses were observed between groups: pathological complete response (31.1% vs 30.3%, P=1.00), major pathological response (44.4% vs 42.9%, P=0.89), and pathological downstaging (67.8% vs 73.9%, P=0.36). Perioperative complication rates, including hematologic toxicities, immune-related adverse events, and surgical complications, were similar (all P>0.05). The tislelizumab group demonstrated significantly lower unplanned ICU transfer rates (P=0.04), while operative parameters (duration, blood loss, R0 resection) showed no differences. CONCLUSION: Tislelizumab-based chemoimmunotherapy demonstrates comparable efficacy and safety to camrelizumab-based regimens, potentially representing a viable neoadjuvant option for locally advanced ESCC.	esophagus