crossing96/oncoscreening huggingface dataset:
Molybdenum Deficiency among Esophageal Cancer Patients.	BACKGROUND: Emerging evidence suggests that deficiencies in trace elements, particularly molybdenum, may contribute to Esophageal Cancer (EC) pathogenesis. Molybdenum is an essential micronutrient that plays a key role in detoxifying carcinogenic compounds through its involvement in enzymatic pathways, including xanthine oxidase activity. This study aims to evaluate serum molybdenum levels in patients with histologically confirmed EC and compare them to healthy controls to assess the association between molybdenum deficiency and EC incidence. MATERIALS AND METHODS: This prospective, single-center observational study was conducted at a regional cancer center in Srinagar, Kashmir, India from June 2021 to June 2023. Patients with histologically confirmed EC were included as the study group, while age- and gender-matched healthy volunteers served as controls. Serum molybdenum levels were measured using atomic absorption spectrophotometry. RESULTS: A total of 400 participants were enrolled. The study group had a mean age of 62.1 ± 12.61 years, with 58.5% males. The mean serum molybdenum level in esophageal cancer patients was significantly lower than that of the control group (0.79 ± 0.452 vs 2.33 ± 0.707, p < 0.001). The gender-based comparison showed that males in the study group had a significantly lower mean serum molybdenum level than male controls (p <0.001), with a similar trend observed in females. CONCLUSION: Molybdenum deficiency may be associated with an increased risk of EC by impairing carcinogen detoxification. Further research is needed to explore its preventive and therapeutic potential.	esophagus
Emerging Challenges of Postendoscopy Esophageal Adenocarcinoma and Postendoscopy Esophageal Neoplasia.	Post-endoscopy esophageal neoplasia (PEEN) and post-endoscopy esophageal adenocarcinoma (PEEC) comprise a significant component of all Barrett's esophagus-related neoplasia diagnoses and rates of PEEN/PEEC may be rising. PEEN/PEEC occur primarily due to missed lesions or rapidly progressive disease. Root-cause analysis should be performed for cases and best practices should be implemented to decrease PEEN/PEEC rates - the most important intervention is a high-quality endoscopic exam. Future efforts should determine the role of biomarkers in identifying individuals at high risk of neoplastic progression, develop additional tissue-sampling techniques to reduce missed lesions, and improve education regarding the principles of a high-quality endoscopic examination.	esophagus
Discovery of W478, a novel SHMT2 inhibitor for the treatment of esophageal carcinoma.	Esophageal cancer has been regarded as a serious malignancy due to its poor prognosis and high mortality rate. Serine hydroxymethyltransferase 2 (SHMT2) is emerging as an attractive target for esophageal cancer therapy. Compound W478 was identified as a potent SHMT2 inhibitor with an IC(50) value of 1.21 μM, especially whose chemical structure is distinct from the reported SHMT2 inhibitors. Both cellular thermal shift assay and isothermal titration calorimetry experiments showed that compound W478 tightly bound to SHMT2 (K(D) = 10.6 ± 1.2 μM). The molecular docking analysis revealed its binding at the folate binding site of SHMT2. Moreover, compound W478 exhibited a significant antiproliferative effect on human esophageal cancer cell lines, KYSE-450 and KYSE-70 cells (IC(50) = 1.62 μM, 1.18 μM, respectively). The wound healing and transwell assays showed that compound W478 could inhibit the migratory and invasive potential of KYSE-450 and KYSE-70 cells in a dose-dependent manner. Further studies demonstrated that compound W478 could induce cell arrest at the G2/M phase and promote cell apoptosis and ROS production in KYSE-450 and KYSE-70 cells. These findings indicated that compound W478 could serve as a promising lead compound for the development of SHMT2 inhibitor to address esophageal carcinoma.	esophagus
Helicobacter pylori in esophageal carcinogenesis: Potential culprit or forceful defender?	Helicobacter pylori (H. pylori), a recognized gastric pathogen, has been extensively documented pertaining to its association with a spectrum of gastrointestinal disorders. Given its predominant dissemination via fecal-oral and oral-oral pathways, H. pylori colonization experiences transient esophageal transit prior to its gastric mucosal establishment, while reflux-mediated recrudescence may result in repetitive exposure. The interplay and causality between H. pylori infection and the onset and development of esophageal carcinoma (EC) has emerged as an area of intense scrutiny. Substantial evidence indicates subtype-dependent associations. H. pylori infection (particularly cytotoxin-associated gene A (CagA)-positive strains) reduces the risk of esophageal adenocarcinoma. However, its relationship with esophageal squamous cell carcinoma remains controversial, with studies reporting positive impact, irrelevance, or even an inverse correlation. This review elucidates H. pylori interactions with EC, summarizes protective and pathogenic mechanisms, discerns extant controversies and clinical implications, to inform novel therapeutic strategies for EC prevention and management.	esophagus
A multimodal synergistic model for personalized neoadjuvant immunochemotherapy in esophageal cancer.	Neoadjuvant immunochemotherapy (nICT) has significantly improved the treatment of locally advanced esophageal cancer (EC), yet accurately identifying patients' response remains a major challenge. In this study, we introduce eSPARK, a multimodal framework designed to integrate routinely available clinical data for informed decision-making in nICT treatment for EC. The model is developed using 344 patients from three independent regions, each with pre-treatment-paired computed tomography (CT) imaging and pathological slides, and postoperative pathological complete response (pCR) outcomes. By incorporating cytological semantic information, eSPARK demonstrates superior generalizability, outperforming single-modality models and achieving robust predictive accuracy across multicenter datasets. Additionally, a multi-scale interpretability module identifies several biomarkers, including the neutrophil-to-lymphocyte ratio (NLR) in the tumor microenvironment, associated with nICT response. Our findings underscore the potential of eSPARK as a powerful tool for personalized therapeutic decision-making in locally advanced EC and its broader implications for advancing precision oncology through multidisciplinary data integration.	esophagus
Advancing immunotherapy for esophageal cancer: decoding the roles of PD-L1, TME, and tumor-intrinsic biomarkers.	Esophageal squamous cell carcinoma (ESCC) remains a global health challenge, with immune checkpoint inhibitors (ICIs) reshaping therapeutic strategies. However, heterogeneous responses underscore the urgent need for robust predictive biomarkers. While PD-L1 expression remains the most widely used marker, its limitations, including spatial heterogeneity and inducible expression, have prompted exploration of alternative and composite indicators. Recent advances highlight the predictive potential of tumor immune microenvironment (TME) features such as tumor-infiltrating lymphocytes (TILs), tertiary lymphoid structures (TLSs), stromal maturity, and T cell-inflamed gene expression profiles. Concurrently, tumor-intrinsic biomarkers, including microsatellite instability, tumor mutational burden, neoantigen load, and chromosomal alterations-have shown promise in stratifying immunotherapy responders. Multi-omics approaches, liquid biopsies, and integration of host factors such as gut microbiota are emerging to refine patient selection. This review comprehensively examines evolving biomarkers and therapeutic trials, emphasizing the need for integrative precision strategies to optimize immunotherapy efficacy in ESCC.	esophagus
Profiling the Chemical Exposomic Landscape of Esophageal Squamous Cell Carcinoma.	While the cancer genome is well-studied, the nongenetic exposome of cancer remains elusive, particularly for regionally prevalent cancers with poor prognosis. Here, by employing a combined knowledge- and data-driven strategy, we profile the chemical exposome of plasma from 53 healthy controls, 14 esophagitis and 101 esophageal squamous cell carcinoma (ESCC) patients, and 46 esophageal tissues across 12 Chinese provinces, integrating inorganic, endogenous, and exogenous chemicals. We first show that components of the ESCC chemical exposome mediate the relationship between ESCC-related dietary/lifestyle factors and clinic health status indicators. Then, the geographic location of patients is revealed to mostly drive the ESCC chemical exposome, exhibiting more pronounced chemical variations in geographically narrower areas of high incidence, with region-specific chemicals, including a probable environmental carcinogen, influencing cancer endemicity. Finally, analysis of cancer evolutionary trajectory indicates major alterations in chemical exposome during disease initiation, suggesting that certain pollutants may hold promise as noninvasive indicators for early disease risk management. Overall, this scalable strategy of profiling chemical exposome provides a blueprint for future exposome-disease studies and highlights the importance of comprehensively considering chemical mixtures to better understand geographic disparities in cancer risk and the etiology of carcinogenesis.	esophagus
The role of ZC3H13 in promoting M2 macrophage infiltration via m6A methylation in esophageal squamous cell carcinoma tumor progression.	INTRODUCTION: ZC3H13 (zinc finger CCCH-type containing 13) is a member of the zinc finger protein family with regulatory roles in gene expression and represents a crucial m6A methyltransferase. However, the precise function of ZC3H13 in the esophageal squamous cell carcinoma tumor microenvironment (TME) remains incompletely understood. Our study primarily investigated the impact of ZC3H13 on m6A methylation modification in ESCC and explored the roles of ZC3H13 and M2 macrophages in ESCC. METHODS: We employed bioinformatics analysis to assess the function of ZC3H13 in ESCC. Quantification of ZC3H13, CCL5, CXCL8, and macrophage infiltration in clinical samples and cell line-derived xenograft (CDX) tumor models was conducted using real-time quantitative PCR (qRT-PCR), western blot (WB), immunohistochemistry (IHC), Immunofluorescence (IF), and Enzyme-linked immunosorbent assay (ELISA). The colorimetric method was utilized to detect m6A methylation in cells and tissues. Tumor proliferation, migration, and invasion were evaluated using CCK8, EdU staining, colony formation tests, transwell assays, and CDX models. RESULTS: We found that elevated ZC3H13 expression was positively correlated with m6A methylation modification in ESCC tumor tissue. ZC3H13 mutation led to abnormal nuclear metastasis of METTL14 and METTL3. Silencing ZC3H13 inhibited ESCC tumor growth and M2 macrophage infiltration in mice. ZC3H13 silencing also suppressed the expression of CCL5 and CXCL8 mRNA. M6A modification enhanced the stability of CXCL8 mRNA. ESCC tumors promoted the polarization of M0-M2 macrophages through the CXCL8-CXCR2 axis, which CXCR2 inhibitors or anti-CXCL8 antibodies could inhibit. Migration of M0 macrophages was facilitated by CCL5. DISCUSSION: Our findings elucidate the connection between ZC3H13-mediated m6A modification and M2 macrophage infiltration in the ESCC-TME, resulting in M2 macrophage polarization and increased M2 macrophage infiltration.	esophagus
Research priorities for cancers of the oesophagus and stomach: recommendations from a UK and Ireland patient and healthcare professional partnership exercise.	BACKGROUND: Cancers of the oesophagus and stomach are a major cause of morbidity and mortality. Research is crucial to improving outcomes. However, to maximise value and impact, areas of focus should be prioritised in partnership with patients. OBJECTIVE: We undertook a comprehensive analysis of UK and Ireland patient and healthcare professional (HCP) priorities for research into oesophagogastric cancers across the domains of prevention, diagnosis and staging, treatment, palliative care and survivorship. DESIGN: A scoping exercise sourced research questions from patients and HCPs. These were consolidated and then confirmed by systematic review to represent a true research uncertainty. Research questions were scored on potential impact by an interdisciplinary group of HCPs and prioritised using a weighting derived from a patient survey. RESULTS: There were 835 (395 HCP, 440 patient) respondents to the scoping (n=455) and prioritisation (n=380) surveys. Across these, 4295 suggested research uncertainties were consolidated to 92 uncertainties that were prioritised. HCP respondents represented 25 professional groups from community and hospital settings. Patient weighting changed 22.2-46.3% of priority rankings established by HCPs. All domains were represented by the 20 highest priority questions, 5 of which focused on personalising and optimally combining treatment modalities. Two other key themes related to optimising nutrition and improving quality of life during and after treatment, including in patients not cured of their cancer. CONCLUSION: This work highlights the impact of patient input on HCP-ranked research priorities and provides a robust list of priorities to guide funders, policymakers and researchers to support and undertake impactful research.	esophagus
Clonal cell states link gastroesophageal junction tissues with metaplasia and cancer.	Barrett's esophagus is a common type of metaplasia and a precursor of esophageal adenocarcinoma. However, the cell states and lineage connections underlying the origin, maintenance, and progression of Barrett's esophagus have not been resolved in humans. Here, we perform single-cell lineage tracing and transcriptional profiling of patient cells isolated from metaplastic and healthy tissue. Our analysis unexpectedly reveals evidence for lineages spanning squamous esophagus, gastric cardia, and transitional basal cells at the tissue junction. We also identify lineages connecting Barrett's esophagus to both esophageal and gastric tissues. Barrett's esophagus biopsies consist of multiple distinct clones, with lineages that contain all progenitor and differentiated cell types. We discover Barrett's esophagus cell types, including tuft, ciliated, and BEST4+ cells, which we validate through both lineage relationships and spatial transcriptomics. In contrast, the precancerous dysplastic lesions show expansion from a single molecularly aberrant Barrett's esophagus clone. Together, these findings provide a single-cell view of the cell dynamics of Barrett's esophagus, linking cell states along the disease trajectory, from its origin to cancer.	esophagus
Endoscopic resection of oesophageal gastrointestinal stromal tumours: Promise, pitfalls and the path forward.	Oesophageal gastrointestinal stromal tumours are rare, anatomically challenging lesions with higher surgical morbidity than their gastric counterparts. Emerging endoscopic resection techniques such as endoscopic submucosal dissection and submucosal tunnelling endoscopic resection show much promise for the management of patients who are not fit for, or wish to avoid the morbidity of, major surgical resection. These techniques require careful patient selection and advanced technical skills. We build on the recent review of such techniques by Vogli et al. Current evidence is limited to small case series with heterogeneity in patient selection, tumor size, and outcomes. Notably, long-term oncological data remain sparse, and complications such as bleeding or perforation may be life-threatening in patients unfit for surgical rescue. Nonetheless, endoscopic approaches have many potential advantages to offer such as preserved quality of life and definitive management of unfit patients.	esophagus
Hsa_circRNA_0101125 Promotes Proliferation, Migration, and Invasion of Esophageal Squamous Cell Carcinoma via miR-143-3p/ZNF148 Axis.	Esophageal squamous cell carcinoma (ESCC) is a highly invasive and metastatic malignancy. Circular RNAs (circRNAs), including hsa_circRNA_0101125, have been implicated in regulating cancer metastasis. But its potential roles in ESCC remain underexplored, particularly in relation to miR-143-3p. This study aimed to investigate the role of hsa_circRNA_0101125/miR-143-3p in the occurrence and development of ESCC. KYSE150 and ECA109 cells were used as in vitro models to evaluate the biological effects of hsa_circRNA_0101125. The interaction between ZNF148 and miR-143-3p was confirmed by dual-luciferase assay. To assess the functional role of this pathway, cells were transfected with sh-hsa_circRNA_0101125 vectors and/or miR-143-3p inhibitors, followed by assays for cell viability (CCK-8), migration (wound healing assay), and invasion (Transwell assay). Transcriptions and expressions of hsa_circRNA_0101125, miR-143-3p, and ZNF148 were measured by RT-qPCR and western blot. Results showed that hsa_circRNA_0101125 was localized in the cytoplasm and negatively regulated miR-143-3p, which targeted ZNF148. Inhibition of hsa_circRNA_0101125 significantly reduced cell viability, migration, and invasion, downregulated ZNF148 and Vimentin, and upregulated miR-143-3p and E-cadherin expressions. In contrast, downregulating miR-143-3p abolished these effects. Therefore, hsa_circRNA_0101125 promotes the proliferation, migration, and invasion of ESCC cells by inhibiting the expression of miR-143-3p.	esophagus
Neoadjuvant CTLA-4/PD-(L)1 Blockade Versus Surgery +/- Chemotherapy in Deficient Mismatch Repair/Microsatellite Instability-High Resectable Gastroesophageal Adenocarcinoma: Individual Patient Data Pooled Analysis.	PURPOSE: Patients with deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) resectable gastroesophageal adenocarcinoma (GEA) have better survival after surgery and scant/no benefit from chemotherapy. Preoperative immune checkpoint inhibitors (ICIs) demonstrated a high proportion of major complete pathologic response, possibly allowing chemotherapy/surgery-free approaches. METHODS: Individual patient data pooled analysis was performed to determine an optimal strategy for resectable dMMR/MSI-H GEA. Patients were stratified across four groups: neoadjuvant dual CTLA-4/PD-(L)1 ICIs with or without surgery, perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) and surgery, and surgery alone or with older perioperative/adjuvant chemotherapy regimens. Primary end points were pathologic complete and major complete pathologic response proportion (pathologic complete response [pCR], tumor regression grade [TRG]1a, major pathologic response [MPR], TRG1a/b Becker criteria) in resected patients. Secondary end points were event-free survival (EFS) and overall survival (OS) in the overall population. RESULTS: Among 197 patients, 49 received ICIs, 27 FLOT, 33 surgery alone, and 88 older chemotherapy regimens. Among 69 patients who underwent surgery after ICIs or FLOT, ICIs demonstrated significantly higher pathologic response versus FLOT (pCR, 61.9% v 3.7%; odds ratio [OR], 54.8; P = .002; MPR, 78.6% v 10%; OR, 39.3; P < .001) and lower ypN+ (14.3% v 37%; OR, 4.2; P = .015) and ypT (OR, 16.4; P < .001) stage. No significant differences in EFS/OS were observed (the 36-month EFS and OS were 70.4% v 80.6% and 72.7% v 90.4% with ICI v surgery alone). Residual nodal disease (ypN+) or ypT4 status after neoadjuvant ICIs or FLOT and nonpathologic response status were associated with inferior progression-free survival/OS. CONCLUSION: In resectable dMMR/MSI-H GEA, neoadjuvant ICIs significantly increase pathologic response and downstaging versus FLOT, with comparable EFS/OS with surgery with or without chemotherapy. The higher proportion of ypN0 and lack of ypT4 after neoadjuvant ICIs versus FLOT should drive preoperative treatment choices in clinical high-risk disease. The high proportion of pCR/MPR with ICIs provides rationale for exploring organ-sparing surgery or nonoperative management.	esophagus
tRNA-derived fragment tRF-24 drives CELF1 phase separation to promote oncogenic splicing in esophageal squamous cell carcinoma.	RATIONALE: Esophageal squamous cell carcinoma (ESCC) is characterized by poor prognosis. tRNA-derived fragments (tRFs), a novel class of non-coding RNAs generated by tRNA cleavage, have emerged as key regulators of cancer development. However, the functional landscape of tRFs remains underexplored in ESCC. We here identified tRF-24-RPM8309M2S (tRF-24), a 5' tRF derived from mature tRNA(LeuAAG/TAG), which promotes the malignant progression of ESCC and offers a promising therapeutic target. METHODS: The public GSE207635 dataset from Gene Expression Omnibus (GEO) database was analyzed to identify tsRNAs involved in ESCC progression. The clinical significance of tRF-24 was investigated in samples from 96 ESCC patients. CUGBP Elav-like family member 1 (CELF1) was validated as a tRF-24 interactor through RNA pull-down assays. CCK-8 and transwell assays were applied to measure malignant cell phenotypes. mCherry-GFP-LC3 reporter assay was performed to examine the autophagy. Colocalization between LC3 and mitochondria was employed to detect mitophagy. Immunofluorescent and colony formation assay were conducted to assess the impact of DNA damage repair and cisplatin resistance in ESCC. Extracellular acidification rate (ECAR), lactate production and glucose consumption were performed to analyze changes in glycolysis. Fluorescence recovery after photobleaching (FRAP) was adopted to evaluate CELF1 phase separation. Additionally, RNA sequencing and alternative splicing analyses were conducted to determine global transcriptome alterations following tRF-24 or CELF1 overexpression. RESULTS: Our findings demonstrate that tRF-24 is significantly upregulated in tumor samples and is associated with poorer survival of ESCC patients. Depletion of tRF-24 suppresses malignant cell phenotypes in ESCC cells both in vitro and in vivo. Mechanistically, tRF-24 binds to the Ser28 residue of CELF1, inhibiting AKT1-mediated phosphorylation at this site, which facilitates CELF1 nuclear translocation and subsequent liquid-liquid phase separation (LLPS) formation. These CELF1-enriched nuclear condensates potently regulate the alternative splicing of BIN1 and BECN1 pre-mRNAs, generating pro-oncogenic BIN1-L and pro-autophagic/mitophagic BECN1-α isoforms that collectively enhance tumor malignancy by promoting tumor cell EMT, DNA damage repair, cisplatin resistance and glycolysis. Targeting tRF-24 with an antagomir significantly suppresses tumor progression in ESCC xenograft models, highlighting its therapeutic potential. CONCLUSIONS: Our findings establish tRF-24 as a promising therapeutic target in the comprehensive treatment of ESCC.	esophagus