Migrasome-related prognostic signature TSPAN4 correlates with immune infiltrates and metabolic disturbances in hepatocellular carcinoma.

IF 6.9 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Journal of Gastroenterology Pub Date : 2025-01-12 DOI:10.1007/s00535-025-02212-4

Xiaoli Zhang, Jianzhou Li, Yichen Yao, Mimi Zhou, Yingli He, Yalei Zhao

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Abstract

Background: We aim to comprehensively analyze and validate the prognostic efficacy of tetraspanin 4 (TSPAN4) and several other migrasome-related markers in hepatocellular carcinoma (HCC).

Methods: The expression, diagnostic, and prognostic efficacy of five migrasome-related genes in HCC were analyzed using several databases. Five pairs of adjacent non-tumor tissues and HCC tissues were used to validate the expression. The prognostic efficacy of TSPAN4 was validated in a HCC cohort. TSPAN4 was knocked down in Huh-7 cells, EdU, and CCK-8, and wound healing assays were conducted to analyze its effects on cell proliferation and migration. In addition, transcriptomic sequencing was used to identify differentially expressed genes.

Results: Compared with those in normal tissues, four genes (TSPAN4, PIGK, NDST1, and CPQ) were elevated in liver hepatocellular carcinoma (LIHC), but not TSPAN7. Of these, only elevated TSPAN4 predicted unfavorable prognosis of HCC patients. The expression and prognostic efficacy of TSPAN4 were further confirmed in a HCC cohort (97 patients); and patients in the TSPAN4^high group showed unfavorable overall survival (log-rank P = 0.0055). Functional analysis showed that TSPAN4 knockdown significantly suppressed cell migration, but not cell proliferation. Moreover, TSPAN4 knockdown induced disturbances of the metabolic pathways, mainly pentose and glucuronate interconversions.

Conclusions: TPSAN4 is a promising prognostic and therapeutic target for HCC treatment and may be involved in the metabolic pathways that affect disease progression.

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与偏头痛相关的预后标志TSPAN4与肝细胞癌的免疫浸润和代谢紊乱相关

背景：我们的目的是全面分析和验证四跨蛋白4 （TSPAN4）和其他几种与迁移体相关的标志物在肝细胞癌（HCC）中的预后疗效。方法：使用多个数据库分析5个迁移体相关基因在HCC中的表达、诊断和预后效果。用5对相邻非肿瘤组织和HCC组织验证表达。在HCC队列中验证了TSPAN4的预后疗效。在Huh-7细胞、EdU和CCK-8中敲除TSPAN4，并进行伤口愈合实验，分析其对细胞增殖和迁移的影响。此外，转录组测序用于鉴定差异表达基因。结果：与正常组织相比，肝癌组织中TSPAN4、PIGK、NDST1、CPQ 4个基因表达升高，而TSPAN7表达不升高。其中，只有TSPAN4升高预示HCC患者预后不良。在HCC队列（97例患者）中进一步证实了TSPAN4的表达和预后疗效；tspan4高组患者总生存期较差（log-rank P = 0.0055）。功能分析显示，TSPAN4敲低可显著抑制细胞迁移，但不抑制细胞增殖。此外，TSPAN4敲低诱导代谢途径紊乱，主要是戊糖和葡萄糖酸盐的相互转化。结论：TPSAN4是HCC治疗的一个有希望的预后和治疗靶点，可能参与影响疾病进展的代谢途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Gastroenterology 医学-胃肠肝病学

CiteScore

12.20

自引率

1.60%

发文量

审稿时长

4-8 weeks

期刊介绍： The Journal of Gastroenterology, which is the official publication of the Japanese Society of Gastroenterology, publishes Original Articles (Alimentary Tract/Liver, Pancreas, and Biliary Tract), Review Articles, Letters to the Editors and other articles on all aspects of the field of gastroenterology. Significant contributions relating to basic research, theory, and practice are welcomed. These publications are designed to disseminate knowledge in this field to a worldwide audience, and accordingly, its editorial board has an international membership.