Zhang Xiaoli, Li Jianzhou, Yao Yichen, Zhou Mimi, He Yingli, Zhao Yalei
Department of Infectious Diseases, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, China.
National Regional Infectious Diseases Center Co-Constructed By National Health Commission of PRC and People's Government of Shaanxi Province, Xi'an, 710061, Shaanxi, China.
J Gastroenterol. 2025 May;60(5):593-606. doi: 10.1007/s00535-025-02212-4. Epub 2025 Jan 12.
We aim to comprehensively analyze and validate the prognostic efficacy of tetraspanin 4 (TSPAN4) and several other migrasome-related markers in hepatocellular carcinoma (HCC).
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.
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 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.
TPSAN4 is a promising prognostic and therapeutic target for HCC treatment and may be involved in the metabolic pathways that affect disease progression.
我们旨在全面分析和验证四跨膜蛋白4（TSPAN4）及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。
利用多个数据库分析了HCC中五个与迁移体相关基因的表达、诊断及预后疗效。使用五对相邻的非肿瘤组织和HCC组织来验证表达情况。在一个HCC队列中验证了TSPAN4的预后疗效。在Huh-7细胞中敲低TSPAN4，进行EdU、CCK-8及伤口愈合实验，以分析其对细胞增殖和迁移的影响。此外，利用转录组测序鉴定差异表达基因。
与正常组织相比，肝肝细胞癌（LIHC）中四个基因（TSPAN4、PIGK、NDST1和CPQ）表达升高，但TSPAN7未升高。其中，只有TSPAN4表达升高预示着HCC患者预后不良。在一个HCC队列（97例患者）中进一步证实了TSPAN4的表达及预后疗效；TSPAN4组患者的总生存期较差（对数秩检验P = 0.0055）。功能分析表明，敲低TSPAN4可显著抑制细胞迁移，但不影响细胞增殖。此外，敲低TSPAN4会导致代谢途径紊乱，主要是戊糖和葡萄糖醛酸相互转化。
TPSAN4是HCC治疗中一个有前景的预后和治疗靶点，可能参与影响疾病进展的代谢途径。
