引用文本：温杰, 施艺, 王志慧, 等. 热休克蛋白家族A成员5在肝细胞癌中的表达及其与细胞转移、增殖及患者不良预后的关系[J/CD]. 消化肿瘤杂志（电子版）, 2026, 18(3): 394-405.

作者：温杰1，施艺1，王志慧1，牛绍清2

单位：1. 中山大学附属第一医院 肿瘤介入科，广东 广州 510080；2. 中山大学附属第一医院 放射治疗科，广东 广州 510080

Authors：Wen Jie1, Shi Yi1, Wang Zhihui1, Niu Shaoqing2

Unit：1. Department of Interventional Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China；2. Department of Radiotherapy, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China

摘要：

目的 探究热休克蛋白家族A成员5（heat shock protein family A member 5, HSPA5）在肝细胞癌（hepatocellular carcinoma, HCC）组织中的表达情况，对HCC患者预后的影响，对Huh7细胞表型行为的影响及其可能机制。方法 利用癌症基因组图谱、基因表达综合数据库和国际癌症基因组联盟的HCC数据，以及HCC组织芯片的免疫组织化学检测，系统分析HSPA5在HCC组织中的表达水平及其与HCC转移风险的关系；通过单因素及多因素Cox比例风险回归模型分析、Kaplan-Meier法探讨HSPA5表达水平对HCC患者预后的影响；利用siRNA技术敲减Huh7细胞中的HSPA5后，通过克隆形成实验、羧基荧光素二醋酸盐琥珀酰亚胺酯（carboxyfluorescein succinimidyl ester, CFSE）细胞增殖检测及Transwell侵袭实验验证HSPA5对Huh7细胞增殖及侵袭能力的影响；通过京都基因和基因组百科全书（Kyoto encyclopedia of genes and genomes, KEGG）及基因本体（gene ontology, GO）富集分析初步探索HSPA5在HCC中潜在的调控机制，并采用蛋白质印迹法检测敲减HSPA5后，Huh7细胞中过氧化物酶体增殖物激活受体（peroxisome proliferator-activated receptor, PPAR）γ的表达水平变化。结果 HSPA5的mRNA及蛋白水平在HCC组织及具有高转移风险的HCC组织中均处于高表达状态。HSPA5高表达是HCC患者预后的独立危险因素。敲减HSPA5可抑制Huh7细胞的侵袭、克隆形成及增殖能力。富集分析显示，HSPA5显著富集于PPAR信号通路、胆汁分泌通路及内质网相关通路等。敲减HSPA5可下调PPARγ蛋白表达水平。结论 HSPA5或可通过激活PPARγ通路促进HCC细胞转移及增殖，是HCC转移相关的潜在标志物及预后预测因子，靶向HSPA5或可为HCC的诊疗提供新思路。

关键词：肝细胞癌；热休克蛋白家族A成员5；肿瘤转移；预后

Abstract：

Objective To investigate the expression of heat shock protein family A member 5 (HSPA5) in hepatocellular carcinoma (HCC) tissues, its prognostic significance for HCC patients, its effects on the phenotypic behaviors of Huh7 cells, and the underlying mechanisms. Method HCC data from the cancer genome atlas (TCGA), gene expression omnibus (GEO), and the International Cancer Genome Consortium (ICGC) were analyzed, along with immunohistochemical staining of an HCC tissue microarray, to systematically evaluate HSPA5 expression levels in HCC tissues and its association with metastatic risk. Univariate and multivariate Cox proportional hazards regression models, and Kaplan-Meier analysis were performed to assess the impact of HSPA5 expression on the prognosis of HCC patients. The siRNA technology was used to knockdown the expression of HSPA5 in Huh7 cells, and then colony formation assay, carboxyfluorescein succinimidyl ester (CFSE) cell proliferation assay, and Transwell invasion assay were conducted to determine the effects of HSPA5 on the proliferation and invasion capacities of Huh7 cells. Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) enrichment analyses were conducted to preliminarily explore the potential regulatory mechanisms of HSPA5 in HCC, followed by validation using western blotting to detect the expression of peroxisome proliferator-activated receptor (PPAR) γ in Huh7 cells after knockdown of HSPA5. Result Both mRNA and protein levels of HSPA5 were highly expressed in HCC tissues and in HCC tissues with high metastatic risk. High HSPA5 expression was identified as an independent risk factor for poor prognosis in HCC patients. Knockdown of HSPA5 significantly inhibited the invasion, colony formation, and proliferation of Huh7 cells. Enrichment analysis revealed that HSPA5 was significantly enriched in pathways including the PPAR signaling pathway, bile secretion, and endoplasmic reticulum-associated pathways in HCC. Notably, knockdown of HSPA5 significantly downregulated the protein expression level of PPARγ. Conclusion HSPA5 may promote HCC metastasis and proliferation through activating the PPARγ signaling pathway. It represents a potential metastasis-associated biomarker and prognostic predictor for HCC. Targeting HSPA5 may provide a new insight for the diagnosis and treatment of HCC.

Key words：Hepatocellular carcinoma; Heat shock protein family A member 5; Metastasis; Prognosis

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