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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

32卷

期数:

2026年03期

页码:

204-212

栏目:

肿瘤疾病专题

出版日期:

2026-05-20

文章信息/Info

Title:

HSF4 promotes the tumorigenesis and progression of prostate cancer and its correlation with EMT

文章编号:

1006-8147（2026）03-0204-09

作者:

左陵凤¹; 李常颖²; 王志强³; 于淼¹; 杨春蕊¹; 邢译文¹; 王兴芬¹; 张向莲¹; 彭双鹤¹; 梁锐¹

1.天津医科大学第二医院病理科，天津300211;2.天津医科大学第二医院泌尿外科研究所，天津300211;3.天津医科大学第二医院肛肠外科，天津300211

Author(s):

ZUO Lingfeng¹; LI Changying²; WANG Zhiqiang³; YU Miao¹; YANG Chunrui¹; XING Yiwen¹; WANG Xingfen¹; ZHANG Xianglian¹; PENG Shuanghe¹; LIANG Rui¹

1.Department of Pathology， The Second Hospital of Tianjin Medical University， Tianjin 300211， China;2.Institute of Urological Surgery， The Second Hospital of Tianjin Medical University， Tianjin 300211， China;3.Department of Colorectal Surgery， The Second Hospital of Tianjin Medical University， Tianjin 300211， China

关键词:

热休克转录因子4; 前列腺癌; 侵袭; 转移; 上皮-间质转化

Keywords:

heat shock transcription factor 4;  prostate cancer;  invasion;  metastasis;  epithelial-mesenchymal transition

分类号:

R737.25

DOI:

10.20135/j.issn.1006-8147.2026.03.0204

文献标志码:

A

摘要:

目的：探讨热休克转录因子4（HSF4）在前列腺癌进展中的作用及其分子机制。方法：基于TCGA数据库获取的转录组与临床数据后，运用R语言“Survival”包进行生存分析，评估HSF4表达与前列腺癌患者预后的相关性。收集天津医科大学第二医院病理科的前列腺癌及配对癌旁组织的石蜡标本，采用免疫组织化学（IHC）技术检测HSF4蛋白在前列腺癌及癌旁组织中的表达水平，分析HSF4表达与临床病理学参数的相关性。利用Western印迹和RT-qPCR技术检测HSF4蛋白、mRNA在人良性前列腺增生细胞系BPH-1及多种人前列腺癌细胞系（22Rv1、PC3、C4-2、DU145、LNCaP）中的表达差异。通过慢病毒介导的RNA干扰技术，在DU145及LNCaP细胞中分别构建对照组（sh-NC）和实验组（sh-HSF4），采用Western印迹和RT-qPCR技术验证HSF4敲低效率。应用CCK-8实验检测细胞增殖能力，划痕实验评估细胞迁移能力，Transwell实验检测细胞侵袭能力。采用Western印迹和RT-qPCR技术检测上皮-间质转化（EMT）关键标志物的表达变化。结果：生信分析显示，HSF4在前列腺癌组织中的表达水平显著高于癌旁组织（P<0.01），且其高表达与患者不良预后显著相关（P<0.05）。组织学实验结果显示：HSF4蛋白在前列腺癌组织中的表达水平显著高于癌旁组织（P<0.0001），且其高表达与患者Gleason评分、临床分期、淋巴结或骨转移显著相关（χ2=9.862，P=0.002；χ2=7.441，P=0.006；χ2=5.478，P=0.019）。细胞学实验结果显示，HSF4在5种人前列腺癌细胞系中的mRNA及蛋白表达水平均显著高于BPH-1细胞（t=16.657、16.594、14.343、18.896、21.29，均P<0.001）。敲低HSF4可显著抑制DU145和LNCaP细胞的迁移、侵袭（t=23.91、17.42，均P<0.001）及增殖能力（t=4.029，P<0.05）。敲低HSF4后，间质标志物N-钙黏蛋白（N-cadherin）和波形蛋白（Vimentin）的表达均显著下调（t=3.867、3.262，均P<0.01），而上皮标志物E-钙黏蛋白（E-cadherin）的表达则显著上调（t=13.27，P<0.001）。结论：HSF4蛋白在前列腺癌组织中高表达，是前列腺癌患者不良预后的潜在生物标志物。HSF4促进前列腺癌的发生、发展，其可能通过调控EMT相关通路参与前列腺癌恶性进程。

Abstract:

Objective： To elucidate the role and molecular mechanism of heat shock transcription factor 4（HSF4） in the progression of prostate cancer（PCa）. Methods： Based on transcriptomic and corresponding clinical data retrieved from The Cancer Genome Atlas （TCGA） database， survival analysis was performed using the‘Survival’package in R to assess the correlation between HSF4 expres-sion levels and prognosis in patient with prostate cancer. A cohort of paraffin-embedded prostate cancer tissues and paired adjacent non-tumor tissues was collected from the Department of Pathology， the Second Hospital of Tianjin Medical University. Immunohisto-chemistry（IHC） was conducted to examine HSF4 protein expression in PCa and adjacent tissues， followed by analysis to evaluating its associations with key clinicopathological parameters. The differential expression of HSF4 at both mRNA and protein levels was ex-amined in the human benign prostatic hyperplasia cell line BPH-1 versus multiple human PCa cell lines（22Rv1， PC3， C4-2， DU145， LNCaP） using Western blotting and RT-qPCR. Lentivirus-mediated RNA interference was employed to establish a control group （sh-NC） and an experimental group（sh-HSF4） in DU145 and LNCaP cells， respectively. The knockdown efficiency of HSF4 was subsequently validated using Western blotting and RT-qPCR. Cell proliferation was assessed by CCK-8 assay， cell migration by wound healing assay， and cell invasion by Transwell assay. Additionally， Western blotting and RT-qPCR were performed to analyze the expression changes of key epithelial-mesenchymal transition（EMT） markers. Results： Bioinformatics analysis showed that the expression level of HSF4 in prostate cancer tissues was significantly higher than that in adjacent tissues（P<0.01）， and its high expre-ssion was significantly correlated with poor prognosis in patients（P<0.05）. Histological experimental results revealed that the protein expression level of HSF4 in prostate cancer tissues was significantly higher than that in adjacent normal tissues（P<0.000 1）， and its high expression was significantly correlated with patients′ Gleason score， clinical stage， and lymph node or bone metastasis（χ2=9.862， P=0.002； χ2=7.441， P=0.006； χ2=5.478， P=0.019）. Cytological experimental results showed that the mRNA and protein expression levels of HSF4 in five human prostate cancer cell lines were significantly higher than those in BPH-1 cells（t=16.657， 16.594， 14.343， 18.896， 21.29， all P<0.001）. Knocking down HSF4 significantly inhibited the migration， invasion（t=23.91， 17.42， both P<0.001）， and proliferation ability（t=4.029， P<0.05） of DU145 and LNCaP cells. After knocking down HSF4， the expression of interstitial markers N-cadherin and Vimentin was significantly downregulated （t=3.867， 3.262； both P<0.01）， while the expres-sion of epithelial marker E-cadherin was significantly upregulated（t=13.27，P<0.001）. Conclusion： HSF4 protein is highly expre-ssed in PCa tissues and represents a potential biomarker for poor prognosis in PCa patients. HSF4 promotes the tumorigenesis and de-velopment of PCa， and potentially facilitate malignant progression of PCa by modulating EMT-related pathways.

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备注/Memo

备注/Memo:

基金项目 国家自然科学基金项目（81660302）；天津医科大学第二医院青年基金（2020ydey20）
作者简介 左陵凤（2002-），女，硕士在读，研究方向：前列腺癌分子机制；通信作者：梁锐，E-mail：ruiliang131@tmu.edu.cn。
（2025-11-05收稿）

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更新日期/Last Update: 2026-05-25