Determining prostate cancer (PCa) aggressiveness and reclassification are critical events during the treatment of localized disease and for patients undergoing active surveillance (AS). Since T cells play major roles in cancer surveillance and elimination, we aimed to identify genetic biomarkers related to T cell cancer immune response which are predictive of aggressiveness and reclassification risks in localized PCa. The genotypes of 3,586 single nucleotide polymorphisms (SNPs) from T cell cancer immune response pathways were analyzed in 1762 patients with localized disease and 393 who elected AS. The aggressiveness of PCa was defined according to pathological Gleason score (GS) and D'Amico criteria. PCa reclassification was defined according to changes in GS or tumor characteristics during subsequent surveillance biopsies. Functional characterization and analysis of immune phenotypes were also performed. In the localized PCa cohort, seven SNPs were significantly associated with the risk of aggressive disease. In the AS cohort, another eight SNPs were identified as predictors for aggressiveness and reclassification. Rs1687016 of PSMB8 was the most significant predictor of reclassification. Cumulative analysis showed that a genetic score based on the identified SNPs could significantly predict risk of D'Amico high risk disease (P-trend = 2.4E-09), GS4 + 3 disease (P-trend = 1.3E-04), biochemical recurrence (P-trend = 0.01) and reclassification (P-trend = 0.01). In addition, the rs34309 variant was associated with functional somatic mutations in the PI3K/PTEN/AKT/MTOR pathway and tumor lymphocyte infiltration. Our study provides plausible evidence that genetic variations in T cell cancer immune response can influence risks of aggressiveness and reclassification in localized PCa, which may lead to additional biological insight into these outcomes. Abbreviations: PCa, prostate cancer; AS, active surveillance; GS, Gleason score; PSA, prostate specific antigen; TCGA, The Cancer Genome Atlas; SNP, single nucleotide polymorphisms; UFG, unfavorable genotype.

中文翻译：

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T细胞癌免疫反应与局部前列腺癌患者的肿瘤侵袭性和主动监测队列中疾病重分类的遗传关联。

确定前列腺癌（PCa）的侵略性和重新分类是治疗局部疾病期间以及进行主动监测（AS）的患者的关键事件。由于T细胞在癌症的监测和消除中起着重要作用，因此我们旨在鉴定与T细胞癌症免疫反应相关的遗传生物标志物，这些标志物可预测局部PCa的侵袭性和重新分类风险。在1762例局部疾病患者和393例选择AS的患者中，分析了来自T细胞癌免疫应答途径的3,586个单核苷酸多态性（SNP）的基因型。PCa的侵袭性根据病理学Gleason评分（GS）和D'Amico标准定义。根据随后的监测活检中GS或肿瘤特征的变化定义PCa重分类。还进行了免疫表型的功能表征和分析。在局部PCa队列中，七个SNP与侵袭性疾病的风险显着相关。在AS队列中，另外八个SNP被确定为攻击性和重新分类的预测因子。PSMB8的Rs1687016是重新分类的最重要预测因子。累积分析表明，基于鉴定出的SNP的遗传评分可以显着预测达米科高危疾病（P-趋势= 2.4E-09），GS4 + 3疾病（P-趋势= 1.3E-04），生化的风险复发（P趋势= 0.01）和重新分类（P趋势= 0.01）。此外，rs34309变体与PI3K / PTEN / AKT / MTOR途径中的功能性体细胞突变和肿瘤淋巴细胞浸润相关。我们的研究提供了可信的证据，表明T细胞癌免疫应答中的遗传变异会影响局部PCa的侵袭性和重新分类风险，这可能导致对这些结果的更多生物学认识。缩写：PCa，前列腺癌；AS，主动监视；GS，格里森得分；PSA，前列腺特异性抗原；TCGA，《癌症基因组图集》；SNP，单核苷酸多态性；UFG，不利的基因型。