crossing96/oncoscreening huggingface dataset:
Single-cell multi-omic and spatial profiling of esophageal squamous cell carcinoma reveals the immunosuppressive role of GPR116(+) pericytes in cancer metastasis.	Tumor metastasis leads to most cancer deaths. However, how cellular diversity and dynamic cooperation within the tumor microenvironment contribute to metastasis remains poorly understood. Here we leverage single-cell multi-omics (16 samples, 117,169 cells) and spatial transcriptomics (five samples, 195,366 cells) to uncover the cellular and spatial architecture of esophageal squamous cell carcinoma (ESCC), and characterize an immunosuppressive GPR116(+) pericyte subset promoting tumor metastasis and immunotherapy resistance. GPR116(+) pericyte enrichment is transcriptionally regulated by PRRX1, evidenced by pericyte-specific Prrx1 knockout mice. Mechanistically, GPR116(+) pericytes secrete EGFL6 to bind integrin β1 on cancer cells, activating the NF-κB pathway to facilitate metastasis. Serum EGFL6 serves as a noninvasive biomarker for the diagnosis and prognosis of several tumors. Blocking integrin β1 suppresses metastasis and improves immunotherapy response in animal models of ESCC. Collectively, we provide a spatially resolved landscape of the prometastatic tumor microenvironment in ESCC and highlight the biological and clinical importance of GPR116(+) pericytes, proposing potential innovative therapeutic strategies for metastatic cancers.	esophagus
[Not Available].	Gastroesophageal cancers still rank among the leading causes of cancer-related death. With the introduction of immunotherapy, the treatment strategy has evolved. In the neoadjuvant setting for gastroesophageal junction (GEJ) and gastric adenocarcinoma, the results of the MATTERHORN clinical trial, presented at this year's ASCO meeting, are expected to shift future treatment strategies. In esophageal tumors, adjuvant nivolumab is used. In metastatic disease, depending on the histological subtype, molecular testing such as PD-L1 CPS and TPS, HER2, and MSI-H is required to determine the treatment decision. In the metastatic setting, combinations of nivolumab or pembrolizumab with fluoropyrimidine- and platinum-based chemotherapy have improved survival. Among HER2-positive patients, adding pembrolizumab to trastuzumab and chemotherapy - in PDL1 CPS ≥1 cases - has become a new standard. A special mention must be made of MSI-H tumors, in which immunotherapy is highly effective, and adjuvant chemotherapy is not recommended according to current guidelines.	esophagus
Focal adhesion kinase/Src family kinase axis-mediated tyrosine phosphorylation of metabolic enzymes facilitates tumor metastasis.	Lymph node metastasis is crucial for esophageal squamous cell carcinoma (ESCC) malignancy. However, the molecular drivers and related mechanisms of lymph node metastasis in ESCC cells are unclear. In the present study, we found that the tyrosine kinase complex-focal adhesion kinase (FAK)/Src family kinase (SFK) axis specifically contributes to metabolic reprogramming by inducing the phosphorylation of ATP-citrate synthase (ACLY) Tyr542, Tyr652, and fructose-bisphosphate aldolase A (ALDOA) Tyr174, Tyr302, or Tyr328 sites in both primary and metastatic ESCC cells. Mechanistically, activated ACLY and ALDOA and their metabolites drive a transcriptional program in primary tumors that induces cyclin-dependent kinase 7/9 (CDK7/9) complex-mediated expression of DNA replication- and cell proliferation-related molecules. This process functions as an enabler of tumor malignancy. In metastatic tumor cells, metabolic enzymes and their products facilitate the transcriptional activity of Yamanaka factors to induce the activation of downstream plasticity-related molecules, fueling ESCC cell survival within metastatic lymph nodes. FAK/SFK axis-controlled ACLY and ALDOA tyrosine phosphorylation and downstream transcription factors and effectors in primary and metastatic ESCC cells are strongly associated with poor patient outcomes. We discovered a lead compound, quercetagitrin, that inhibits the phosphorylation of ALDOA at Tyr174, 302, and 328. Moreover, it has been shown to have antitumor effects alone or in combination with FAK/SFK inhibitors both in vivo and in vitro. The inhibition of tyrosine kinase-regulated metabolic enzyme activities and related signaling networks may be a potential strategy for the treatment and diagnosis of metastatic ESCC.	esophagus
H2BC9 lactylation modulates esophageal squamous cell carcinoma progression via the Wnt/β-catenin signaling pathway.	BACKGROUND: Lactate, traditionally regarded as a metabolic waste product of glycolysis, has recently emerged as a critical signaling molecule and epigenetic modifier via protein lactylation. However, the functional consequences of histone lactylation in cancer progression remain poorly understood. METHODS: We integrated transcriptomic data from TCGA and GEO (GSE188900) with bulk and single-cell RNA-seq analyses to identify lactylation-associated histone variants involved in esophageal squamous cell carcinoma (ESCC). Functional assays, immunoprecipitation (IP), western blotting (WB), chromatin immunoprecipitation (ChIP)-qPCR, and luciferase reporter assays were employed to investigate the role of H2BC9 and its lactylation in ESCC. A xenograft tumor model was used to validate in vivo relevance. RESULTS: We identified H2BC9, a histone H2B variant, as a lactylation-associated oncogene that is overexpressed in ESCC and correlates with poor prognosis. Lactate stimulation induced H2BC9 lactylation, particularly at lysine 44 (K44), as confirmed by mass spectrometry and IP-WB assays. Mechanistically, K44 lactylation of H2BC9 enhanced the transcriptional activity of Wnt7b, leading to activation of the Wnt/β-catenin pathway. Mutation of K44 (K44R) abolished H2BC9 lactylation and significantly impaired its ability to promote ESCC cell proliferation and Wnt7b transcription, as demonstrated by ChIP-qPCR and dual-luciferase assays. In vivo, H2BC9 K44R-expressing cells exhibited reduced tumor growth in xenograft models. Furthermore, H2BC9 expression was associated with an immunosuppressive tumor microenvironment and chemoresistance. CONCLUSION: Our study reveals a novel regulatory axis in which H2BC9 K44 lactylation activates Wnt7b transcription and downstream Wnt/β-catenin signaling, driving ESCC progression. Targeting H2BC9 lactylation may offer a promising therapeutic strategy to overcome tumor growth and immune evasion in ESCC.	esophagus
Surveillance of Barrett's Esophagus.	Surveillance of Barrett's esophagus is essential for preventing and detecting esophageal cancer, particularly esophageal adenocarcinoma. This article examines the importance of ongoing surveillance before and after Barrett's endoscopic treatment to reduce the risk of progression to high-grade dysplasia or esophageal adenocarcinoma. It highlights the emerging role of adjunctive testing, including biomarkers, advanced imaging, and artificial intelligence to improve diagnostic accuracy. Additionally, the article reviews the latest clinical guidelines for surveillance intervals and timing. Overall, this article aims to provide insights into the evolving landscape of Barrett's Esophagus surveillance.	esophagus
A circRNA promotes esophageal squamous cell carcinoma progression by inhibiting TRIM25-mediated degradation of IGF2BP family members.	"BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with poor prognosis and limited treatment options. While circular RNAs (circRNAs) are frequently dysregulated in ESCC, their functional roles and molecular mechanisms in tumor progression remain largely unexplored. METHODS: We characterized circRNA using RT-PCR, Sanger sequencing, and fluorescent in situ hybridization. Gain- and loss-of-function studies in vitro and in vivo were performed to assess circRNA function. Molecular interactions were investigated via RNA pull-down assays coupled with mass spectrometry, electrophoretic mobility shift assays, co-immunoprecipitation, and immunoblot analysis. Clinical relevance was evaluated by RT-qPCR and immunohistochemistry in patient specimens. RESULTS: We identified circLNF, a novel circRNA derived from the long non-coding RNA FIRRE gene, which is significantly upregulated in ESCC. Functional assays demonstrated that circLNF promotes proliferative and migratory capacities in cultured cells and accelerates tumor progression and metastasis in animal models. Mechanistically, circLNF directly interacts with IGF2BP family proteins through their ""CAUC"" motifs, protecting them from TRIM25-mediated ubiquitination and proteasomal degradation. Importantly, circLNF expression positively correlated with IGF2BP1 protein levels in ESCC patient tissues, underscoring the clinical relevance of the circLNF-IGF2BP axis in ESCC progression. CONCLUSIONS: Our findings reveal an oncogenic role of circLNF in ESCC by inhibiting TRIM25-mediated proteasomal degradation of IGF2BP proteins and highlight circLNF as a potential therapeutic target for ESCC."	esophagus
Single-cell atlas of the esophageal squamous cell carcinoma immune ecosystem to predict immunotherapy response.	Esophageal squamous cell carcinoma (ESCC) evolves within a highly interactive tumor microenvironment (TME) that shapes therapeutic response. We utilized mass cytometry to analyze over 10 million cells from 25 ESCC tumors, 24 adjacent nontumor tissues, and 23 peripheral blood samples, employing an extensive panel of 42 immune markers. The resulting atlas reveals a compartmentalized landscape with a reproducible paucity of CD4⁺ and CD8⁺ central memory T cells (TCM) in tumor sites. Reintroduction of patient-derived TCMs restored antitumor immunity in coculture assays, demonstrating their cytotoxic capacity in vitro and suggesting their potential relevance for future therapeutic exploration. Myeloid profiling identified PD-L1⁺ tumor-associated macrophages (TAMs) as correlates of clinical benefit; ex vivo PD-L1 blockade reprogrammed TAMs toward proinflammatory states, indicating pharmacological malleability. Notably, CD39⁺ tumor-infiltrating T cells were consistently associated with favorable prognosis and increased responsiveness to PD-1 blockade across cancer types. The functional inhibition of CD39 impaired cytotoxic T-cell activity, underscoring its dual role as a marker of immune dysfunction and a promising therapeutic target. Collectively, our findings provide a comprehensive immune landscape of ESCC, highlighting key immunological deficits and opportunities for targeted interventions. The insights gained underscore the potential of tailoring immunotherapies to the specific immune profiles of the TME, potentially revolutionizing treatment paradigms for ESCC patients. This study sets the stage for a more nuanced understanding and manipulation of the immune elements critical for optimizing cancer immunotherapy.	esophagus
Emerging Biomarkers for Managing Barrett's Esophagus.	Comparative analyses of normal esophageal tissue, Barrett's Esophagus (BE), and esophageal adenocarcinoma have identified distinctive molecular alterations in genomic DNA, epigenetics, non-coding RNA, and proteins that have shown promise as disease-specific biomarkers. Some of the best characterized and promising biomarkers for managing BE are multi-target esophageal cytology DNA assays based on methylated-DNA and immunohistochemical staining of Trefoil factor 3. Additional biomarkers including microRNA, measures of genomic instability, mixed-method panels, and other novel biomarkers (e.g. volatile organic compounds and saliva microbiome) remain in early development and will need further validation in large, prospective studies prior to clinical use.	esophagus
Adiposity distribution and risks of 12 obesity-related cancers: a Mendelian randomization analysis.	INTRODUCTION: There is convincing evidence that overall adiposity increases the risks of several cancers. Whether the distribution of adiposity plays a similar role is unclear. METHODS: We used 2-sample Mendelian randomization (MR) to examine causal relationships of 5 adiposity distribution traits (abdominal subcutaneous adipose tissue (ASAT); visceral adipose tissue (VAT); gluteofemoral adipose tissue (GFAT); liver fat; and pancreas fat) with the risks of 12 obesity-related cancers (endometrial, ovarian, breast, colorectal, pancreas, multiple myeloma, liver, kidney (renal cell), thyroid, gallbladder, esophageal adenocarcinoma, and meningioma). RESULTS: Sample size across all genome-wide association studies (GWAS) ranged from 8407 to 728 896 (median: 57 249). We found evidence that higher genetically predicted ASAT increased the risks of endometrial cancer, liver cancer, and esophageal adenocarcinoma (odds ratios (OR) and 95% confidence intervals (CI) per standard deviation (SD) higher ASAT = 1.79 (1.18 to 2.71), 3.83 (1.39 to 10.53), and 2.34 (1.15 to 4.78), respectively). Conversely, we found evidence that higher genetically predicted GFAT decreased the risks of breast cancer and meningioma (ORs and 95% CIs per SD higher genetically predicted GFAT = 0.77 (0.62 to 0.97) and 0.53 (0.32 to 0.90), respectively). We also found evidence for an effect of higher genetically predicted VAT and liver fat on increased liver cancer risk (ORs and 95% CIs per SD higher genetically predicted adiposity trait = 4.29 (1.41 to 13.07) and 4.09 (2.29 to 7.28), respectively). DISCUSSION: Our analyses provide novel insights into the relationship between adiposity distribution and cancer risk. These insights highlight the potential importance of adipose tissue distribution alongside maintaining a healthy weight for cancer prevention.	esophagus
Quality Management of Barrett's Esophagus.	Barrett's Esophagus (BE) is a key precursor to esophageal adenocarcinoma that requires quality management to improve patient outcomes. This article explores current evidence-based practices in the diagnosis, surveillance, and endoscopic treatment of BE, with a focus on quality indicators including biopsy protocols, dysplasia detection techniques, and adherence to surveillance intervals. We examine emerging technologies, such as image-enhanced endoscopy and artificial intelligence, with emphasize on the importance of training, audit, and standardization in clinical practice. By aligning care with established quality benchmarks, clinicians can enhance the early detection and prevention of neoplastic progression in patients with BE.	esophagus
Endoscopic Screening of Barrett's Esophagus.	Endoscopic Barrett's esophagus (BE) screening detects premalignant changes, enabling the detection of BE and endoscopic surveillance to detect dysplasia/esophageal adenocarcinoma (EAC). Endoscopic therapy for BE dysplasia reduces EAC risk and can treat early stage EAC effectively. Screening is advised for those with multiple risk factors: chronic reflux, age over 50 years, male sex, Caucasian race, smoking, central obesity, hiatal hernia, or family history. Risk prediction tools are evolving. High-definition endoscopy with biopsies enables detection; precise landmark identification is key.	esophagus
m6A-mediated circG3BP1 translocation to stress granules promotes nucleation and senescence-linked chemoresistance.	RNAs and RNA-binding proteins (RBPs) play crucial roles in stress granule (SG) dynamics, yet the specific interactions between SG-associated circular RNAs (circRNAs) and RBPs in esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, we identified m6A-modified circG3BP1 as a potential prognostic biomarker in ESCC. Under cisplatin-induced stress, IGF2BPs facilitate the m6A-dependent translocation of circG3BP1 to SGs, where it functions as a scaffold to enhance TIAR-CAPRIN1 interactions, thereby promoting SG nucleation. SG formation suppresses the translation of senescence-associated mRNAs, such as p21, delaying chemotherapy-induced cellular senescence and contributing to cisplatin resistance in ESCC cells. Clinically, elevated circG3BP1 expression is associated with cisplatin resistance in patients with ESCC. These findings reveal a previously uncharacterized m6A-dependent mechanism by which circG3BP1 promotes SG-mediated chemoresistance, providing a promising potential biomarker and therapeutic target for ESCC treatment.	esophagus
ctDNA detects residual disease after neoadjuvant chemoradiotherapy and guides adjuvant therapy in esophageal squamous cell carcinoma.	The diagnostic accuracy of circulating tumor DNA (ctDNA) for detecting molecular residual disease (MRD) after multimodal treatment remains unclear. In a prospective cohort of 132 patients with locally advanced esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (nCRT) followed by clinical response evaluation and surgery, tumor-informed personalized-panel and fixed-panel ctDNA assays are applied to serial blood samples. Personalized ctDNA assay demonstrates a superior baseline detection rate (99.2%) and outperforms fixed panels in diagnosing post-nCRT residual disease. Integrating personalized ctDNA with conventional clinical diagnostic methods increases sensitivity for predicting non-pathological complete response (non-pCR) from 78.4%-80.7% to 92.0%-93.2%. Patients with detectable MRD post-nCRT and/or post-surgery exhibit worse survival outcomes. In non-pCR patients, adjuvant immunotherapy improves disease-free survival in post-surgery MRD-positive cases, whereas MRD-negative patients derive no benefit. These findings support incorporating ctDNA into response assessment to guide organ-sparing strategies and adjuvant therapy decisions in ESCC. This study is registered at ClinicalTrials.gov (NCT03937362).	esophagus
Chelerythrine inhibits esophageal squamous cell carcinoma progression via PINK1-Parkin-mediated mitophagy.	BACKGROUND: Chelerythrine (CHE) exhibits notable anti-inflammatory and antitumor properties, while its impact on esophageal squamous cell carcinoma (ESCC), especially the underlying mechanisms remain unclear. In this study, we aim to investigate the roles and mechanism of CHE in the ESCC treatment. METHODS: Human ESCC cell lines and organoids were used for in vitro cell experiments, BALB/c nude mice were used for in vivo animal experiments. To investigate the underlying mechanism of CHE treatment, drug library screen, RNA sequencing analysis, TMT-based quantitative proteomic analysis, western blotting analysis, immunofluorescence, immunohistochemistry, quantitative real-time polymerase chain reaction, mitochondrial membrane potential assay, apoptosis assay, detection of mitochondrial reactive oxygen species (mtROS), autophagic flux monitoring, transmission electron microscopy, and seahorse XF-96 metabolic flux analysis were used to assess the effect of CHE and relevant mechanism. RESULTS: CHE dose-dependently inhibited the proliferation, migration, and invasion of ESCC cells. CHE also induced cell apoptosis and triggered PTEN-induced kinase 1 (PINK1)-Parkin-mediated mitophagy-mediated cell death by elevating the production of reactive oxygen species in mitochondria and diminishing mitochondrial membrane potential (MMP). However, the production of autophagosomes and autolysosomes induced by CHE altered when used in combination with the autophagy inhibitors 3-methyladenine (3-MA) or bafilomycin A1 (BafA1), indicating that it induced complete autophagic flux in the cells. Mechanistically, CHE affected multiple signaling pathways associated with ubiquitin-mediated proteolysis, mitophagy, and mitochondrial energy metabolism, indicating its close involvement in mitophagy occurrence. In addition, CHE treatment significantly reduced tumor size and weight in nude mice bearing KYSE150 tumors and retarded the growth of organoids derived from patients, it also reduced the ratio of M2 macrophage in tumor microenvironment and cell metabolism. CONCLUSIONS: CHE activates PINK1-Parkin-mediated mitophagy and disrupts mitochondrial homeostasis, and it also affects the tumor environment and cell metabolism, ultimately leading to cell death, supporting the potential of CHE for ESCC therapy.	esophagus
Artificial intelligence in medical imaging empowers precision neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma.	Neoadjuvant immunochemotherapy (nICT) has demonstrated significant potential in improving pathological response rates and survival outcomes for patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, substantial interindividual variability in therapeutic outcomes highlights the urgent need for more precise predictive tools to guide clinical decision-making. Traditional biomarkers remain limited in both predictive performance and clinical feasibility. In recent years, the application of artificial intelligence (AI) in medical imaging has expanded rapidly. By incorporating voxel-level feature maps, the combination of radiomics and deep learning enables the extraction of rich textural, morphological, and microstructural features, while autonomously learning high-level abstract representations from clinical CT images, thereby revealing biological heterogeneity that is often imperceptible to conventional assessments. Leveraging these high-dimensional representations, AI models can provide more accurate predictions of nICT response. Future advancements in foundation models, multimodal integration, and dynamic temporal modeling are expected to further enhance the generalizability and clinical applicability of AI. AI-powered medical imaging is poised to support all stages of perioperative management in ESCC, playing a pivotal role in high-risk patient identification, dynamic monitoring of therapeutic response, and individualized treatment adjustment, thereby comprehensively advancing precision nICT.	esophagus