Wu Xiangkun, Lv Daojun, Eftekhar Md, Khan Aisha, Cai Chao, Zhao Zhijian, Gu Di, Liu Yongda
Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, Guangzhou, China.
Transl Androl Urol. 2020 Dec;9(6):2572-2586. doi: 10.21037/tau-20-1019.
Biochemical recurrence (BCR) is considered a decisive risk factor for clinical recurrence and the metastasis of prostate cancer (PCa). Therefore, we developed and validated a signature which could be used to accurately predict BCR risk and aid in the selection of PCa treatments.
A comprehensive genome-wide analysis of data concerning PCa from previous datasets of the Cancer Genome Atlas (TCGA) and the gene expression omnibus (GEO) was performed. Lasso and Cox regression analyses were performed to develop and validate a novel signature to help predict BCR risk. Moreover, a nomogram was constructed by combining the signature and clinical variables.
A total of 977 patients were involved in the study. This consisted of patients from the TCGA (n=405), GSE21034 (n=131), GSE70770 (n=193) and GSE116918 (n=248) datasets. A 9-mRNA signature was identified in the TCGA dataset (composed of C9orf152, EPHX2, ASPM, MMP11, CENPF, KIF4A, COL1A1, ASPN, and FANCI) which was significantly associated with BCR (HR =3.72, 95% CI: 2.30-6.00, P<0.0001). This signature was validated in the GSE21034 (HR =7.54, 95% CI: 3.15-18.06, P=0.019), GSE70770 (HR =2.52, 95% CI: 1.50-4.22, P=0.0025) and GSE116918 datasets (HR =4.75, 95% CI: 2.51-9.02, P=0.0035). Multivariate Cox regression and stratified analysis showed that the 9-mRNA signature was a clinical factor independent of prostate-specific antigen (PSA), Gleason score (GS), or AJCC T staging. The mean AUC for 5-year BCR-free survival predictions of the 9-mRNA signature (0.81) was higher than the AUC for PSA, GS, or AJCC T staging (0.52-0.73). Furthermore, we combined the 9-mRNA signature with PSA, GS, or AJCC T staging and demonstrated that this could enhance prognostic accuracy.
The proposed 9-mRNA signature is a promising biomarker for predicting BCR-free survival in PCa. However, further controlled trials are needed to validate our results and explore a role in individualized management of PCa.
生化复发（BCR）被认为是前列腺癌（PCa）临床复发和转移的决定性风险因素。因此，我们开发并验证了一种可用于准确预测BCR风险并辅助PCa治疗选择的特征。
对来自癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）先前数据集的PCa数据进行了全面的全基因组分析。进行了套索回归和Cox回归分析，以开发和验证一种有助于预测BCR风险的新型特征。此外，通过结合该特征和临床变量构建了列线图。
共有977名患者参与了该研究。这包括来自TCGA（n = 405）、GSE21034（n = 131）、GSE70770（n = 193）和GSE116918（n = 248）数据集的患者。在TCGA数据集中鉴定出一种由9个mRNA组成的特征（由C9orf152、EPHX2、ASPM、MMP11、CENPF、KIF4A、COL1A1、ASPN和FANCI组成），其与BCR显著相关（HR = 3.72，95%CI：2.30 - 6.00，P < 0.0001）。该特征在GSE21034（HR = 7.54，95%CI：3.15 - 18.06，P = 0.019）、GSE70770（HR = 2.52，95%CI：1.50 - 4.22，P = 0.0025）和GSE116918数据集中得到验证（HR = 4.75，95%CI：2.51 - 9.02，P = 0.0035）。多变量Cox回归和分层分析表明，9个mRNA组成的特征是独立于前列腺特异性抗原（PSA）、 Gleason评分（GS）或美国癌症联合委员会（AJCC）T分期的临床因素。9个mRNA组成的特征对5年无BCR生存预测的平均AUC（0.81）高于PSA、GS或AJCC T分期的AUC（0.52 - 0.73）。此外，我们将9个mRNA组成的特征与PSA、GS或AJCC T分期相结合，证明这可以提高预后准确性。
所提出的9个mRNA组成的特征是预测PCa无BCR生存的有前景的生物标志物。然而，需要进一步的对照试验来验证我们的结果，并探索其在PCa个体化管理中的作用。
