前列腺癌中STEAP4表达与肿瘤浸润T淋巴细胞的相关性研究

Correlation between STEAP4 expression and tumor-infiltrating T lymphocytes in prostate cancer

摘要

目的 分析前列腺六次跨膜上皮抗原4（STEAP4）在前列腺癌（PCa）中的表达情况，探讨其表达与肿瘤浸润T淋巴细胞中的调节性T细胞（Tregs）、CD8+ T细胞浸润的相关性，预测其在促进PCa进展中的潜在作用。方法 回顾性收集2018年1月-2024年12月于川北医学院附属南充市中心医院接受根治性前列腺切除术的90例PCa患者的临床病理资料和肿瘤组织标本，通过免疫组化技术检测肿瘤组织中STEAP4、叉头框转录因子P3（FoxP3）及CD8+ T细胞的蛋白表达水平，分析STEAP4表达水平与Tregs（FoxP3+ T细胞）、CD8+ T细胞浸润的相关性以及STEAP4表达水平与患者临床病理特征间的关联性，采用Kaplan-Meier生存曲线分析STEAP4表达水平与患者预后的关系。结果 STEAP4在PCa组织中的表达水平显著高于癌旁良性前列腺组织（P＜0.001）；STEAP4表达水平与血清总前列腺特异性抗原（tPSA）水平、精囊腺侵犯、前列腺外扩散、国际泌尿病理学会（ISUP）分级分组及病理T分期显著相关（均P＜0.05）。在PCa组织中Tregs（FoxP3+T细胞）的平均浸润密度显著高于癌旁良性前列腺组织[（11.09±5.05）个/HPF对比（3.92±1.59）个/HPF，P＜0.001]，CD8+ T细胞的平均浸润密度显著低于癌旁良性前列腺组织[（6.07±2.90）个/HPF对比（27.23±6.75）个/HPF，P＜0.001]。在PCa组织中，STEAP4表达水平与Tregs（FoxP3+T细胞）浸润密度呈显著正相关（r_s=0.472，P＜0.001），与CD8+ T细胞浸润密度呈显著负相关（r_s=-0.495，P＜0.001）。Kaplan-Meier生存曲线显示，STEAP4高表达组与低表达组PCa患者的总生存率及无复发生存率的差异均无统计学意义（P=0.562，0.346）。结论 本研究初步分析发现，STEAP4在PCa组织中高表达，其表达水平与肿瘤浸润T淋巴细胞中的Tregs、CD8+ T细胞浸润密切相关，提示STEAP4表达可能与Tregs及CD8+ T细胞共同参与肿瘤免疫微环境调控，进而促进PCa进展。

Abstract

Objective To investigate the expression of six-transmembrane epithelial antigen of prostate 4 (STEAP4) in prostate cancer (PCa), explore its correlation with the infiltration of regulatory T cells (Tregs) and CD8+ T cells within the tumor-infiltrating T lymphocyte population, and to predict the potential role of STEAP4 in promoting PCa progression. Methods The clinicopathological data and tumor tissue specimens were collected from 90 PCa patients undergoing radical prostatectomy at our hospital during Jan.2018 and Dec.2024. The protein expressions of STEAP4, forkhead box transcription factor P3 (FoxP3), and CD8+ T cells in tumor tissues were detected with immunohistochemistry. The correlation between STEAP4 expression and the infiltration of Tregs (FoxP3 T cells), CD8+ T cells and clinicopathological characteristics was analyzed. The relationship between STEAP4 expression and prognosis was evaluated with Kaplan-Meier survival curves. Results STEAP4 expression was significantly higher in PCa tissues than in adjacent benign tissues (P＜0.001). STEAP4 expression was significantly associated with serum total prostate-specific antigen (tPSA) level, seminal vesicle invasion, extraprostatic extension, International Society of Urological Pathology (ISUP) grading, and pathological T stage (all P＜0.05). The mean infiltration density of Tregs (FoxP3 T cells) in PCa tissues was significantly higher than that in adjacent benign tissues [(11.09±5.05) cells/HPF vs. (3.92±1.59) cells/HPF, P＜0.001], while the mean infiltration density of CD8+ T cells was significantly lower [(6.07±2.90) cells/HPF vs. (27.23±6.75) cells/HPF, P＜0.001]. In PCa tissues, STEAP4 expression showed a significant positive correlation with Treg (FoxP3 T cells) infiltration density (r_s=0.472, P＜0.001) and a significant negative correlation with CD8+ T-cell infiltration density (r_s= -0.495, P＜0.001). Kaplan-Meier survival curves indicated that high STEAP4 expression group and low STEAP4 expression group in PCa patients was not correlated with overall survival (OS) or recurrence-free survival (P =0.562, 0.346). Conclusion STEAP4 is highly expressed in PCa tissues, and its expression is closely associated with tumor-infiltrating lymphocytes, particularly Tregs and CD8+ T cells, suggesting that STEAP4 may cooperate with Tregs and CD8+ T cells to regulate the tumor microenvironment, thereby promoting PCa progression.

关键词

前列腺癌 / 前列腺6跨膜上皮抗原4（STEAP4） / 肿瘤微环境 / 肿瘤浸润淋巴细胞 / 调节性T细胞 / FoxP3+ T细胞 / CD8+ T细胞

Key words

prostate cancer / six-transmembrane epithelial antigen of prostate 4 (STEAP4) / tumor microenvironment / tumor-infiltrating T lymphocytes / regulatory T cells / forkhead box transcription factor P3 (FoxP3) / CD8+ T cells

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