Luowei Wang

Dysregulated splicing factors play critical roles in tumor progression. Here, we identify family with sequence similarity 50 member A (FAM50A) as a pivotal oncogenic splicing factor involved in esophageal squamous cell carcinoma (ESCC). Multi-omics and multi-cohort analyses revealed that FAM50A is upregulated in ESCC and correlates with a poor prognosis. Functional studies demonstrated that FAM50A promotes ESCC proliferation and migration both in vitro and in vivo, primarily through the activation of mitogen-activated protein kinases (MAPKs) and focal adhesion kinase (FAK). We further characterized the FAM50A-binding RNA motif and established its transcriptome-wide splicing landscape. Notably, we identified a novel FAM50A-dependent backsplicing event that generates circSDK1, which originates from exons 2–4 of the sidekick cell adhesion molecule 1 (SDK1) pre-mRNA. Mechanistically, circSDK1 binds to dual-specificity phosphatase 22 (DUSP22) and occupies its phosphatase domain, inhibiting the DUSP22-mediated dephosphorylation of MAPKs and FAK and thereby sustaining their activation. Furthermore, the transcription factor TFAP2C increased FAM50A expression. Finally, we identified rifabutin as a small-molecule inhibitor of FAM50A and confirmed its anti-tumor efficacy in cell-derived xenograft, patient-derived organoid, and patient-derived xenograft models. In summary, FAM50A promotes ESCC progression via the FAM50A/circSDK1/DUSP22 axis, leading to MAPKs and FAK activation. Genetic or pharmacological targeting of FAM50A with rifabutin represents a promising therapeutic strategy for ESCC.

Esophageal squamous cell carcinoma (ESCC) is highly lethal owing to its early and aggressive metastasis, yet the underlying multi-layer molecular mechanism

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Non-variceal upper gastrointestinal bleeding (NVUGIB) poses significant mortality risk in critically ill patients, necessitating accurate early prognostic

Background/Objectives: The association between gastroesophageal reflux disease (GERD) and extraesophageal malignancies remains unclear. This study aimed to systematically evaluate the relationship between GERD and these cancers. Methods: PubMed, Embase, Scopus, Cochrane Library, and Web of Science were searched for studies reporting risk estimates—risk ratios (RRs), odds ratios (ORs), hazard ratios (HRs), or standardized incidence ratios (SIRs)—of GERD and extraesophageal malignancies. Mendelian randomization (MR) studies with available risk estimates and 95% confidence intervals (CIs) were also included. Pooled estimates with 95% CIs were calculated using a random-effects model. Results: As of 21 May 2025, a total of 37 studies were included in the analysis. GERD was significantly associated with an increased risk of several extraesophageal malignancies, including pharyngeal cancer (pooled RR = 2.04; 95% CI: 1.38–3.02), with a particularly high risk observed for hypopharyngeal cancer (RR = 2.95; 95% CI: 1.99–4.37; I² = 60.24%). Elevated risks were also identified for laryngeal cancer (RR = 2.23; 95% CI: 1.41–3.52) and lung cancer (RR = 1.20; 95% CI: 1.01–1.42). No significant association was found between GERD and colorectal cancer (RR = 1.19; 95% CI: 0.68–2.09), and findings regarding oral cancer were inconsistent across studies. Six MR studies confirmed a positive causal relationship between GERD and lung cancer, while one MR study suggested a potential causal association with oral cancer and another with pancreatic cancer. Conclusions: Our findings suggest that GERD may be a significant risk factor for pharyngeal, laryngeal and lung cancers. Appropriate evaluation and surveillance in patients with GERD may be warranted.

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.

Section Background and Objective Over the past decade, transcription factors (TFs) have emerged as key players in various diseases. Immunotherapy has gained traction as an effective treatment, despite resistance to immune checkpoint inhibitors remains a challenge. The regulatory role of TFs in immunotherapy for esophageal squamous cell carcinoma (ESCC) is poorly understood. This study aims to explore the expression of key TFs, predictive significance, and tumor microenvironment (TME) cell infiltration in ESCC. AbstractSection Methods The expression profiles were obtained from Gene Expression Omnibus (GEO) databases, TF gene data were obtained from the Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining (TTRUST) database. A protein-protein interaction (PPI) network and enrichment analysis elucidated the molecular processes in ESCC. We investigated the TME cell infiltration landscape in a combined ESCC cohort. The relative abundance of cell infiltration was measured using a single-sample gene-set enrichment analysis (ssGSEA). The diagnostic value of hub TFs for ESCC was investigated using ROC analysis. AbstractSection Results This study found 48 differentially expressed TFs between normal and ESCC tissues and revealed a strong association between EZH2, FOS, KLF4, FOSB, TWIST1, KLF6 and CEBPB. The results suggested that upregulated EZH2, TWIST1, and KLF4 correlated with immunosuppressive cell infiltration (Tregs, MDSCs) and reduced PD-1/PD-L2 checkpoint expression. Downregulated FOSB and CEBPB associated with enhanced NK cell activity. The diagnostic potential of these key transcription factors in ESCC was evaluated through ROC analysis (EZH2, area under the curve [AUC] = 0.95; TWIST1, AUC = 0.85; CEBPB, AUC = 0.84; FOSB, AUC = 0.79; KLF4, AUC = 0.97; FOS, AUC = 0.84; KLF6, AUC = 0.84). Single-cell data confirmed TF expression in tumor cells, macrophages, and T-cell subsets, highlighting their role in TME remodeling. AbstractSection Conclusion The scRNA-seq analysis revealed the expression of hub TFs in different cell clusters. The study investigated the expression of DETFs associated with patient prognosis and TME cell infiltration in ESCC.

Background: China has made significant progress in medical accessibility and quality over the past decades, and quality improvements in gastroenterology and digestive endoscopy have been consistent. The study aimed to describe the status quo of gastroenterology and digestive endoscopy in the Chinese mainland based on the data from the National Clinical Improvement System (NCIS) and the Hospital Quality Monitoring System (HQMS). Methods: Data were extracted from the NCIS and the HQMS. Data analysis included general information from the Department of Gastroenterology and Endoscopy centers, management of inpatients and outpatients, and annual volume and quality indicators of digestive endoscopy. Acute pancreatitis, gastrointestinal bleeding, inflammatory bowel disease, and cirrhosis were identified as priority diseases and were subjected to detailed analysis. Results: Data from 4620 and 7074 hospitals were extracted from the NCIS and HQMS, respectively. In 2023, 9.6 gastroenterologists, 6.7 endoscopists, and 37.3 gastroenterology beds per hospital nationwide were observed, achieving 19,252.4 outpatient visits, 1615.2 hospitalizations (97.0 for acute pancreatitis, 146.1 for gastrointestinal bleeding, 40.2 for inflammatory bowel disease, and 111.4 for cirrhosis), and 9432.7 digestive endoscopic procedures per hospital. Overall, the quality of practice improved significantly. The proportion of early cancer among gastrointestinal cancers increased from 11.1% in 2015 to 23.4% in 2023, and the adenoma detection rate during colonoscopy increased from 19.3% in 2019 to 26.9% in 2023. Regarding priority diseases, hospitalizations increased, and 31-day unplanned readmission rates decreased between 2019 and 2023. The median hospitalization costs and median proportion of medication costs decreased for acute pancreatitis, gastrointestinal bleeding, and cirrhosis. However, it increased for inflammatory bowel disease. Conclusion: This report evaluates the status quo and development of gastroenterology and digestive endoscopy in the Chinese mainland, providing guidance for future quality improvements.