A novel 8-gene panel for prediction of early biochemical recurrence in patients with prostate cancer after radical prostatectomy.

列线图 生化复发 断点群集区域 前列腺癌 前列腺切除术 肿瘤科 基因签名 医学 一致性 内科学 比例危险模型 转移 基因表达谱 癌症研究 癌症 基因 基因表达 生物 遗传学 受体
作者
Jinan Guo,Chang Zhao,Xinzhou Zhang,Wu Zhong,Tingting Chen,Jiashun Miao,Jinping Cai,Wenchuan Xie,Hao Chen,Mengli Huang,Xiaochen Zhao,Wei Wei,Qi Shen
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期刊:PubMed 卷期号:12 (7): 3318-3332 被引量:3
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Approximately 25% of prostate cancer (PCa) cases experience biochemical recurrence (BCR) following radical prostatectomy (RP). The patients with BCR, especially with BCR ≤2 year after RP (early BCR), are more likely to develop clinical metastasis and castration resistance. Now decision-making regarding BCR after RP relies solely on clinical parameters. We thus attempted to establish an early BCR-risk prediction model by combining a molecular signature with clinicopathological features for guiding clinical decision-making. In this study, an 8-gene signature was derived, and these eight genes were SPTBN2, LGI3, TGM3, LENG9, HAS3, SLC25A27, PCDHGA1, and ADPRHL1. The Kaplan-Meier analysis revealed a significantly prolonged BCR-free survival in the patients with low-risk scores compared to those with high-risk scores in both training and validation datasets. Harrell's concordance index and time-dependent receiver operating characteristic analysis demonstrated that this gene signature tended to outperform three commercial panels at early BCR prediction. Moreover, this signature was also proven as an independent predictor of BCR-free survival. A nomogram, incorporating the gene signature and clinicopathologic features, was constructed and excellently predicted 1-, 2- and 3-year BCR-free survival of localized PCa patients after RP. Gene set enrichment analysis, tumor immunity, and mRNA expression profiling analysis showed that the high-risk group was more prone to the immunosuppressive microenvironment and impaired DNA damage response than the low-risk group. Collectively, we successfully developed a novel 8-gene signature as a powerful predictor for early BCR after RP and created a prognostic nomogram, which may help inform the clinical management of PCa.

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