Aims: Prostate cancer (PCa) presents ongoing challenges in differentiating aggressive from indolent disease using traditional biomarkers such as prostate-specific antigen (PSA). The Phosphatase and Tensin Homolog (PTEN), a key tumour suppressor involved in cellular growth regulation, is emerging as a promising biomarker for risk stratification. This meta-analysis aims to evaluate the prognostic significance of PTEN loss in PCa, particularly its relationship with Gleason grade groups (GG), as defined by the ISUP system, and clinical outcomes. Methods: A systematic review and meta-analysis of 16 studies encompassing 11,375 patients was conducted in accordance with PRISMA guidance. Studies included evaluated PTEN loss, stratified by hemizygous and homozygous deletions, and its association with GG and clinical endpoints such as biochemical recurrence and lethal progression. Pooled odds ratios (ORs) and hazard ratios (HRs) were calculated using a random-effects model. Results: PTEN loss was significantly associated with tumour aggressiveness. Compared to GG1 tumours, the odds of PTEN loss were markedly increased in Gleason GG 2 and 3(OR: 2.78, 95% CI: 1.95–3.61) and GG ≥ 4 (OR: 6.35, 95% CI: 5.37–7.33). Homozygous PTEN deletions were more strongly associated with high-grade tumours than hemizygous deletions. Clinically, PTEN loss was predictive of adverse outcomes, including increased risk of biochemical recurrence (HR: 1.78, 95% CI: 1.31–2.25) and lethal progression (HR: 2.57, 95% CI: 1.12–3.95). Conclusion: PTEN loss correlates with higher GG and poorer clinical outcomes in PCa. Incorporating PTEN assessment into clinical decision making could improve risk stratification, guiding early intervention strategies and identifying patients suitable for active surveillance.
目的：前列腺癌（PCa）在利用前列腺特异性抗原（PSA）等传统生物标志物区分侵袭性与惰性疾病方面持续面临挑战。磷酸酶与张力蛋白同源物（PTEN）作为参与细胞生长调控的关键肿瘤抑制因子，正逐渐成为风险分层中具有前景的生物标志物。本荟萃分析旨在评估PTEN缺失在前列腺癌中的预后意义，特别是其与国际泌尿病理学会（ISUP）系统定义的格里森分级组（GG）及临床结局之间的关系。 方法：依据PRISMA指南，对涵盖11,375例患者的16项研究进行了系统综述与荟萃分析。纳入研究评估了PTEN缺失（按半合子与纯合子缺失分层）及其与GG、生化复发和致死性进展等临床终点的关联。采用随机效应模型计算汇总比值比（OR）与风险比（HR）。 结果：PTEN缺失与肿瘤侵袭性显著相关。与GG1肿瘤相比，格里森GG2和3级（OR：2.78，95% CI：1.95–3.61）及GG≥4级（OR：6.35，95% CI：5.37–7.33）肿瘤中PTEN缺失的几率显著增加。纯合子PTEN缺失较半合子缺失与高级别肿瘤的关联更为密切。在临床结局方面，PTEN缺失可预测不良预后，包括生化复发风险升高（HR：1.78，95% CI：1.31–2.25）和致死性进展风险增加（HR：2.57，95% CI：1.12–3.95）。 结论：PTEN缺失与前列腺癌更高的格里森分级组及更差的临床结局相关。将PTEN评估纳入临床决策可优化风险分层，从而指导早期干预策略并识别适合主动监测的患者。
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