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Purpose: The complexity and heterogeneity of the tumor immune microenvironment (TIME) are linked to the development and poor prognosis of hepatocellular carcinoma (HCC). However, the cell type within the TIME that is most closely associated with HCC development remains unclear. Herein, we aimed to identify cell clusters that significantly contribute to HCC development and their underlying mechanisms.
Method And Results: Using single-cell RNA sequencing (scRNA-seq), we analyzed changes in the TIME of normal and tumor tissues, identifying plasma cells as the key cluster in HCC development. Based on plasma cell-related genes (PCRGs), we constructed and validated an eight-gene prognostic model (ST6GALNAC4, SEC61A1, SSR3, RPN2, PRDX4, TRAM1, SPCS2, CD79A) using internal and external datasets and a nomogram. Functional enrichment, miRNA network construction, and transcriptional regulation analyses were performed to explore underlying mechanisms. TIDE scores and the GDSC database were used to predict immunotherapy and chemotherapy sensitivity in different risk groups. Finally, SSR3's biological function was validated in vitro in HCC cell lines.
Conclusion: Plasma cells are key clusters in HCC development. A prognostic model based on the PCRGs can accurately predict the prognosis of patients with HCC and guide clinical treatment.
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http://dx.doi.org/10.2147/JHC.S509749 | DOI Listing |
Ann Surg Oncol
September 2025
Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Background: Hepatocellular carcinoma (HCC) frequently invades the portal vein, leading to early recurrence and a poor prognosis. However, the mechanisms underlying this invasion remain unclear. In this study, we aimed to detect portal vein circulating tumor cells (CTCs) using a Glypican-3-positive detection method and evaluate their prognostic significance.
View Article and Find Full Text PDFVet Res Commun
September 2025
Department of Animal Industry Convergence, Kangwon National University, Chuncheon, 24341, Republic of Korea.
Global warming causes heat stress in livestock, impairing their health, welfare, and productivity. In bovines, chronic stress elevates cortisol levels; however, this response often goes undetected due to the lack of practical biomatrices for accurate assessment. Common biomatrices such as blood require repeated sampling that may affect measurement accuracy.
View Article and Find Full Text PDFJ Viral Hepat
October 2025
Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Discontinuing antivirals in chronic hepatitis B virus (HBV) 'e' antigen negative infection can enhance HBV surface antigen (HBsAg) loss but risks complications. We modelled the clinical impact of discontinuing antivirals in chronic HBV. We developed a Markov state model with Monte Carlo simulation of chronic HBV to compare continuation of antiviral therapy with 3 strategies of cessation and reinitiation for: (1) virologic relapse, (2) clinical relapse, or (3) hepatitis flare.
View Article and Find Full Text PDFJ Proteome Res
September 2025
State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Research Unit of Proteomics & Research and Development of New Drug of Chinese Academy of Medical Sciences, Institute of Lifeomics, Beijing 102206, China.
Hepatocellular carcinoma (HCC) constitutes approximately 90% of liver cancers, yet its early detection remains challenging due to the low sensitivity of current diagnostic methods and the difficulty in identifying minimal cancer cells within the body. This study employed a patient-derived xenograft (PDX) mouse model to screen for biomarkers, leveraging its advantage of low background interference compared to human serum exosome studies. Using a novel microextraction technique, exosomes were isolated from just one microliter of serum from HCC PDX mice, followed by proteomic profiling.
View Article and Find Full Text PDFJ Gastroenterol Hepatol
September 2025
Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea.
Objective: Hepatocellular carcinoma (HCC) can still occur in patients with chronic hepatitis C after achieving a sustained virologic response (SVR) with direct-acting antiviral (DAA) therapy. Therefore, we aimed to identify and validate predictors and HCC risk models using longitudinal data.
Method: This retrospective cohort study included patients who achieved SVR after DAA therapy.