crossing96/oncoscreening huggingface dataset:
A Novel TRG-N Prognostic Classification System for Esophageal Cancer Undergoing Neoadjuvant Therapy Followed by Esophagectomy: A Study Based on the Netherlands Cancer Registry.	OBJECTIVE: To develop a new prognostic classification system centered on tumor regression grade (TRG) and ypN stage that can effectively stratify overall survival (OS) of esophageal cancer patients undergoing neoadjuvant therapy followed by R0 esophagectomy. BACKGROUND: Although the prognostic value of combining TRG and ypN stage has been demonstrated, a prognostic classification system integrating these factors, trained using large-scale data, remains unavailable. METHODS: Data from the Netherlands Cancer Registry (2015-2022) were analyzed. A new TRG-N prognostic classification system for OS was developed by grouping patients based on cN stage, ypN stage, and TRG. The prognostic performance of the TRG-N classification was compared with the eighth edition AJCC ypTNM classification using 4 comparative metrics [log-rank χ², linear trend χ², Akaike information criterion (AIC), and C-index]. RESULTS: A total of 3193 patients were included. Among patients with adenocarcinoma, the TRG-N classification showed superior linear trend χ² and AIC to the ypTNM classification. However, the log-rank χ² of the TRG-N classification was inferior to that of the ypTNM classification, with no significant difference in the C-index ( P =0.206) between the 2 systems. Among patients with squamous cell carcinoma, the TRG-N classification significantly outperformed the ypTNM classification in log-rank χ², linear trend χ², AIC, and C-index ( P =0.018). CONCLUSIONS: The TRG-N classification demonstrated comparable prognostic performance to the AJCC ypTNM classification for esophageal adenocarcinoma but showed superior prognostic value for esophageal squamous cell carcinoma, making it a potentially more effective tool for risk stratification in esophageal cancer patients.	esophagus
Integrative GEO and Mendelian randomization analysis reveals transcriptomic and lipidomic features of esophageal adenocarcinoma.	BACKGROUND: The incidence of esophageal adenocarcinoma (EA) has significantly increased in developed Western countries. Despite medical advancements, the prognosis remains poor, with a 5-year survival rate of less than 20%. By 2024, the global incidence is expected to reach 141,300 new cases annually, underscoring the urgent need to elucidate the mechanisms underlying EA pathogenesis to develop effective preventive and therapeutic strategies. METHODS: To identify differentially expressed genes (DEGs) linked to EA, microarray datasets sourced from the Gene Expression Omnibus (GEO) database were scrutinized, incorporating 4 datasets that met the defined criteria. Using expression quantitative trait loci and Mendelian randomization (MR) analyses, the contribution of genetic factors to EA development was evaluated. Functional pathways were explored using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis, which revealed enrichment in lipid metabolism. Consequently, Bayesian-weighted MR analysis was performed on 179 plasma lipid subgroups. RESULTS: We identified 492 DEGs, 211 of which were downregulated and 281 were upregulated. The MR analysis identified 178 genes with significant causal effects on EA. Four co-expressed genes were ultimately determined: FZD2, KRT23, and CES1 were significantly upregulated in EA and positively associated with its occurrence, whereas ALDOC (aldolase, fructose-bisphosphate C) was inversely associated with EA risk. Elevated levels of sphingomyelins, sterol esters, diacylglycerols, and triacylglycerols were linked to a reduced risk of EA, whereas high levels of phosphatidylethanolamine correlated with a heightened risk. CONCLUSIONS: Integration of DEGs, expression quantitative trait loci, and lipidomics data provides robust insights into the molecular mechanisms of EA. These findings provide a promising foundation for the development of novel targeted therapies.	esophagus
Prognostic and clinicopathological significance of tertiary lymphoid structure in esophageal squamous cell carcinoma: a systematic review and meta-analysis review.	Tertiary lymphoid structures (TLS), ectopic immune cell aggregates in non-lymphoid tissues, have emerged as potential predictors of esophageal squamous cell carcinoma (ESCC) outcomes. Given increasing evidence, we conducted an updated meta-analysis to systematically evaluate their prognostic and clinicopathological significance. A comprehensive literature search was performed through PubMed, Embase, Web of Science, Scopus, and Cochrane Library (up to June 2024) for studies assessing TLS associations with TNM staging and survival outcomes (OS/PFS) in ESCC. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random-effects models. This meta-analysis incorporated seven studies comprising nine separate datasets that evaluated the impact of TLS in ESCC. The pooled analysis demonstrated a significant positive correlation between TLS presence and more advanced T stage (OR = 2.65, 95%CI: 1.86-3.78; p < 0.01) but not N stage (OR = 1.27, 95%CI: 0.85-1.89; p = 0.24). Additionally, TLS presence was significantly associated with enhanced overall survival (HR = 0.49, 95%CI: 0.41-0.58, p < 0.01) as well as progression-free survival (HR = 0.56, 95%CI: 0.45-0.69, p < 0.01). Notably, when assessed using combined HE and IHC criteria, the prognostic benefit of TLS was more pronounced, with HRs further decreasing to 0.40 (95% CI: 0.31-0.51) for OS and 0.50 (95% CI: 0.41-0.60) for PFS. These findings confirm that the presence of TLS, particularly when verified through combined HE staining and IHC, is an independent favorable prognostic factor in ESCC patients.	esophagus
Establishment and validation of survival nomogram score staging for esophageal squamous cell carcinoma patients after minimally invasive surgery combined with immune prognostic index and clinicopathological features.	BACKGROUND: Minimally invasive esophagectomy (MIE) is commonly applied in the treatment of esophageal squamous cell carcinoma (ESCC). The preoperative immune prognostic index (IPI) is considered a potential indicator for ESCC. In this study, we attempted to establish and validate a comprehensive clinical risk staging toward predicting the long-term outcome in ESCC patients after MIE through the combined application of IPI and clinicopathological features based on nomogram. METHODS: Patients diagnosed with ESCC and who were treated with MIE at our center were randomly assigned in a 7:3 ratio to two cohorts: training (n=425) and validation (n=188). Nomograms were then established according to the Cox multivariate results for the training cohort. To evaluate the predictive value and the clinical benefit rate of the nomogram, we employed the calibration curve, decision curve analysis (DCA), and time-dependent area under the curve (t-AUC). The best cut-off value obtained was applied to develop the survival nomogram-scoring (SNS) staging. RESULTS: Patients with ESCC and who underwent MIE exhibited the worse overall survival (OS) and disease-free survival (DFS) with an IPI=2 relative to IPI=0 or 1 (all P < 0.001) in the training and validation cohorts, respectively. According to the multivariate Cox analysis, we established nomograms that combined IPI with the clinicopathological features to predict the OS and DFS. The t-AUC and DCA demonstrated that the nomograms had a better predictive value and clinical benefit rate than the American Joint Committee on Cancer (AJCC) staging. Accordingly, we developed the SNS staging and found that the OS and DFS were significantly different among patients at different stages (all P < 0.001). The dynamic mortality risk rate revealed a double peak in the high-risk patients (12 and 48 months) and a single peak in the low-risk patients (24 months) and middle-risk patients (12 months), which gradually decreased over time. CONCLUSION: The SNS staging based on IPI and clinicopathological features can thus be applied to effectively evaluate the OS and DFS of ESCC patients after MIE. Our findings may facilitate the development of clinical follow-up strategies.	esophagus
Innovations in Nonendoscopic Screening in Barrett's Esophagus.	The goal of this review is to describe data for nonendoscopic screening techniques for the detection of Barrett's esophagus (BE). Endoscopic screening is currently the primary modality for BE detection. A more effective strategy could use risk-based models that integrate clinical factors and are embedded in electronic health records to guide screening. High-risk patients may need endoscopy, while low-risk patients could benefit from less invasive tools like cell collection devices with biomarkers. Integrating BE screening into primary care will be critical in improving early detection of esophageal adenocarcinoma.	esophagus
Induction of CXCL8 by endoplasmic reticulum stress promotes migration and invasion of esophageal squamous cell carcinoma through activation of SMAD2/3.	Endoplasmic reticulum stress (ERS) is a protective stress response aimed at mitigating its own abnormal proteins, which is closely associated with tumors. However, the molecular mechanism of ERS in the pathogenesis of esophageal squamous cell carcinoma (ESCC) remains unclear. In the present study, RNA sequencing was carried out in the ESCC ERS cell model in vitro, and differentially expressed genes were screened, among which CXCL8 with exhibited differential expression which was studied. CXCL8 was significantly upregulated after thapsigargin (TG; an ERS inducer) treatment in ESCC cells. A marked elevated expression of CXCL8 and its receptors were observed in ESCC cells. CXCL8 was induced by the IRE1α and PERK pathways of ERS, transcription of which was activated by the downstream transcription factors XBP1 and ATF4. TG and rh‑CXCL8 facilitated migration and invasion of ESCC cells, and the migration and invasion effect of TG on ESCC cells could be partially prevented by knockdown of CXCR1. Furthermore, CXCL8‑CXCR1 could activate SMAD2/3 and the activation of SMAD2/3 directly or indirectly regulated the transcription of SNAI2 and ZEB1 to promote the progression of epithelial‑mesenchymal transition (EMT) in ESCC. Both in vivo experiments and immunohistochemical analyses further demonstrated the oncogenic effects of CXCL8. In conclusion, the data obtained in the present study indicated that CXCL8 may be induced via the IRE1α/XBP1 and PERK/ATF4 pathways, and that the CXCL8‑CXCR1/2‑SMAD2/3‑SNAI2/ZEB1 axis is involved in the EMT process of ER‑stressed ESCC cells. Thus, blocking the CXCL8‑CXCR1/2 axis may disrupt ERS‑induced migration and invasion of ESCC cells, thereby improving the prognosis of patients with ESCC.	esophagus
Pathological responses to neoadjuvant immunochemotherapy: implications for survival and recurrence in patients with locally advanced esophageal squamous cell carcinoma.	BACKGROUND: This study evaluated the prognostic implications of pathological responses of primary tumors (PTs) and lymph nodes (LNs) among locally advanced esophageal squamous cell carcinoma (LA-ESCC) patients received neoadjuvant immunotherapy combined with chemotherapy (nICT). METHODS: This study enrolled patients with LA-ESCC who underwent nICT combined with esophagectomy at Jiangsu Cancer Hospital. Two senior pathologists independently and systematically evaluated the postoperative pathological specimens in a double-blind manner. Tumor regression in PTs was assessed using the Becker criteria, while LNs regression grading was optimized using Harrell's concordance index and the Akaike Information Criterion. The primary endpoints were overall survival (OS) and progression-free survival (PFS), with recurrence patterns as the secondary endpoint. RESULTS: A total of 141 patients with 141 PTs and 2,316 LNs were reviewed. LNs regression classified as LNs complete response (LN-CR); Partial/Poor response (LN-PR); and Truly negative LNs (LNN). The ypT0N0 rate was 21.3%. With median 41-months follow-up (IQR 22-55), the 3-year OS and PFS rates were 61.7% (95% CI 53.3-69.1%) and 48.2% (95% CI 40.2-56.4%), respectively. PTs regression grade was an independent prognostic factor for both OS and PFS (P < 0.05). Multivariable analysis demonstrated that a poorer tumor regression grade (TRG) was significantly associated with increased risks of OS and PFS (P < 0.05). Furthermore, while complete LN-CR correlated with improved PFS compared to LN-PR (P = 0.037), this association did not retain statistical significance in the multivariate analysis. Non-ypT0N0 patients exhibited higher recurrence rates than ypT0N0 (52.3% vs 33.3%, P = 0.047), primarily manifested as mixed progression. CONCLUSIONS: PTs response may constitute a more prominent determinant of both OS and PFS than LNs status, and combining these factors enhances prognostic prediction.	esophagus
Comprehensive analysis based on the ubiquitination- and deubiquitylation-related genes reveals the function of NEURL3 in esophageal squamous cell carcinoma.	BACKGROUND: As a highly invasive gastrointestinal malignancy, esophageal squamous cell carcinoma (ESCC) carries with its high morbidity and mortality. Accumulating evidence indicates that abnormal activation of ubiquitination and deubiquitylation has been implicated in pathophysiology of ESCC. However, rare prognostic models for ubiquitination-related genes (URGs) and deubiquitylation-related genes (DRGs) have been built up in ESCC. METHODS: From training dataset GSE53624, the differentially expressed prognostic URGs and DRGs were identified to develop a prognostic signature, which was validated in GSE53622 and TCGA-ESCC dataset to show the robustness of the signature. To further confirm their prognosis value, the unsupervised clustering analysis was used to develop the molecular subtypes based on the prognostic URGs and DRGs. Differences in terms of biological function, immune status, and drug sensitivity were evaluated between high- and low-risk groups. The nomogram was constructed by combining the URGs and DRGs prognostic signature and clinical characteristics to improve prediction efficacy. Loss-of-function studies were conducted to explore the biological function of NEURL3 in ESCC. RESULTS: The URGs and DRGs prognostic signature consisted of 11 genes and exhibited high accuracy in predicting prognosis of ESCC patient. Based on these 11 URGs and DRGs, two molecular subtypes of ESCC (C1 and C2) were identified, of which C2 subtype had significantly shorter overall survival time than that of C1 subtype. The function enrichment analysis showed that these genes play key roles in essential processes such as tumor metastasis and immune response. Moreover, the risk score was closely related to infiltration abundance of some types of immune cells, gene markers of immune cells and immune checkpoint-related markers. The drug sensitivity analysis showed that dacomitinib and talazoparib may serve as anti-ESCC drugs through targeting MAPK14. The nomogram was established by combining the URGs and DRGs signature with age and TNM stage, and it also showed enhanced prognostic predictive accuracy. The in vitro experiments showed that knockdown of NEURL3 inhibited the proliferation and motility of ESCC cells. CONCLUSIONS: Based on the URGs and DRGs prognostic signature, a novel nomogram was constructed that could serve as a potentially reliable prognostic model and provide theoretical basis for uncovering potential therapeutic target in the treatment of ESCC.	esophagus
Environmental exposure to perfluorooctane sulfonate and its role in esophageal cancer progression: a comprehensive bioinformatics and experimental study.	Esophageal cancer (ESCA) is a significant malignancy with rising global incidence rates and considerable impacts on patient survival and quality of life. Current diagnostic and therapeutic strategies face limitations, necessitating research into its underlying mechanisms and potential biomarkers for early diagnosis. This study aims to investigate the role of perfluorooctane sulfonate (PFOS), an environmental toxicant, in the development of ESCA through a comprehensive bioinformatics approach. Using the TCGA-ESCA dataset, we identified differentially expressed genes (DEGs) and intersected them with PFOS-related toxicity targets predicted via Comparative Toxicogenomics Database (CTD) and SuperPred. Machine learning (Random Forest, XGBoost, LASSO, SVM) were applied to prioritize core targets. Survival analysis, in vitro qPCR (ESO-26/FLO-1 cells), and molecular docking were performed. Immune infiltration and pathway activity (GSVA) were assessed. We identified 98 PFOS-related DEGs in ESCA, enriched in hypoxia response, epithelial migration, and cancer-associated pathways (e.g., AGE-RAGE, PI3K-Akt). Machine learning highlighted three core targets: PLAU, TOP2A, and BAX. High expression of these genes correlated with poor survival (PLAU, p = 0.047) and was upregulated in ESCA tissues. PFOS exposure significantly elevated their expression in esophageal cancer cells. Molecular docking revealed strong binding affinities between PFOS and core targets. GSVA linked PLAU/TOP2A/BAX to oncogenic pathways (angiogenesis, DNA repair), while immune analysis showed PLAU's association with stromal infiltration and TOP2A's negative correlation with CD8 + T cells. PFOS exacerbates ESCA by dysregulating PLAU, TOP2A, and BAX, which drive tumor progression via immune modulation, genomic instability, and oncogenic signaling. These targets may serve as biomarkers and therapeutic vulnerabilities for PFOS-associated ESCA, underscoring the need for environmental regulation and targeted therapies.	esophagus
Interpretable multimodal radiopathomics model predicting pathological complete response to neoadjuvant chemoimmunotherapy in esophageal squamous cell carcinoma.	BACKGROUND: Accurate preoperative prediction of pathological complete response (pCR) following neoadjuvant chemoimmunotherapy (nCIT) could help individualize treatment for patients with esophageal squamous cell carcinoma (ESCC). This study aimed to develop and externally validate an interpretable multimodal machine learning framework that integrates CT radiomics and H&E-stained whole-slide images pathomics to predict pCR. METHODS: In this multicenter, retrospective study, 335 patients with ESCC who received nCIT followed by esophagectomy were enrolled from three institutions. Patients from one center were divided into a training set (181 patients) and an internal test set (115 patients), while data from the other two centers comprised an external test set (39 patients). We developed unimodal radiomics and pathomics models, and two multimodal fusion models-an intermediate fusion model (MIFM) and a late fusion model (MLFM). Model performance was evaluated using the area under the curve (AUC), accuracy, sensitivity, specificity, and F1 score, with exploratory survival stratification by observed and model-predicted pCR status. Interpretability was treated as a design constraint and operationalized at both the feature and model levels. RESULTS: The MIFM outperformed unimodal models and the MLFM across all cohorts, achieving AUC/accuracy/sensitivity/specificity/F1 score of 0.97/0.93/0.84/0.96/0.86 (training set), 0.78/0.87/0.62/0.93/0.63 (internal test set), and 0.76/0.77/0.54/0.88/0.61 (external test set). Both observed and predicted pCR status showed exploratory prognostic stratification for overall survival. Feature definitions were mathematically or morphologically explicit, and case-level/cohort-level explanations together with decision-pathway views provided insights into model reasoning. We additionally provide a user-friendly Graphical User Interface to facilitate clinical practice. CONCLUSIONS: We developed and externally validated an interpretable radiopathomics fusion framework that predicts pCR after nCIT in ESCC using standard-of-care data. This model holds promise as an effective tool for guiding individualized decisions between surveillance and timely surgery.	esophagus
Serum multiomics prediction of prognosis and adverse reactions to concurrent chemoradiotherapy in patients with esophageal cancer.	OBJECTIVE: Concurrent chemoradiotherapy (CCRT) is an important treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC). There is still a lack of reliable means to predict efficacy, prognosis and hematologic toxicity. DESIGN: We analyzed 127 serum samples before CCRT and 93 serum samples after CCRT from 127 ESCC patients via metabolomics by GC-MS. Combined with Olink proteomics, we constructed models to predict response and survival through machine learning. Multiple linear regression was used to construct hematologic toxicity prediction models. In combination with the proteomics of ESCC, metabolic changes were studied. RESULTS: A prediction model for the efficacy to CCRT was established via serum metabolomics and proteomics (Train, CR/nCR = 28/50, AUC = 0.9848, 95% CI = 0.9639-1.0000; Test, CR/nCR = 17/15, AUC = 0.8854, 95% CI = 0.7800-0.9908). A survival prediction model was established (n = 109, C-index = 0.7640, 95% CI = 0.7140-0.8140). Linear models for predicting hematologic toxicity were constructed (n = 111, R > 0.7). L-serine is important for the prognosis of patients with ESCC treated with CCRT, and SHMT2 is a key protein in serine metabolism that affects the efficacy of CCRT. CONCLUSION: The combination of serum metabolomics with proteomics can effectively predict the prognosis and hematologic toxicity, which can provide important data for patients to choose treatment methods.	esophagus
Cadonilimab combined with taxane and cisplatin as the first-line treatment of advanced esophageal squamous cell carcinoma: an open-label, multicenter phase II trial.	BACKGROUND: Cadonilimab, a bispecific antibody simultaneously targeting programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4, may further boost antitumor activity compared with PD-1 or programmed cell death ligand 1 (PD-L1) inhibitors. Here, we evaluated the safety and efficacy of cadonilimab combined with chemotherapy as the first-line treatment in advanced esophageal squamous cell carcinoma (ESCC). METHODS: Treatment-naïve patients with unresectable locally advanced or metastatic ESCC were eligible. Cadonilimab combined with paclitaxel or nab-paclitaxel and cisplatin was administrated for up to six cycles, then cadonilimab monotherapy continued as maintenance until progressive disease or unacceptable toxicity, with a maximum of 24 months. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. Plasma cell-free DNA samples were collected before and after treatment and prepared for DNA methylation level sequencing. RESULTS: As of September 27, 2024, 43 patients were enrolled with a median age of 61 years (range 44-75), 39.5% had PD-L1 combined positive score ≥10 and 95.3% had distant metastases. The ORR was 81.4% (95% CI 66.6% to 91.6%) and DCR was 97.7% (95% CI 86.2% to 99.9%). The median PFS was 7.10 months (95% CI 5.68 to 8.48) while OS remained immature. The mean pretreatment cytosine-phosphate-guanine (CpG) site methylation levels of APBA2, EPAS1, TRIM58, ITPKA and LINC00554 were significantly higher in responders than those in non-responders. Grade 3-4 treatment-related adverse events were reported in 53.5% (23/43) patients. CONCLUSIONS: Cadonilimab combined with taxane and cisplatin as first-line treatment revealed encouraging antitumor activity and manageable safety in patients with advanced ESCC. DNA methylation level might be a potential biomarker for guiding patient outcomes. TRIAL REGISTRATION NUMBER: NCT05522894.	esophagus