Exploration of the Tumor Mutational Burden as a Prognostic Biomarker and Related Hub Gene Identification in Prostate Cancer.
Exploration of the Tumor Mutational Burden as a Prognostic Biomarker and Related Hub Gene Identification in Prostate Cancer.
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DOI：
10.1177/15330338211052154
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发表时间：
2021-01
影响因子：
2.8
通讯作者：
Hong Z
中科院分区：
文献类型：
--
作者：
Wang L;Yao Y;Xu C;Wang X;Wu D;Hong Z
为了探讨肿瘤突变负荷(TMB)和潜在的生物标志物在前列腺癌(PCa)中的标志性作用，从癌症基因组图谱(TCGA)数据库下载了转录组图谱、体细胞突变数据和临床病理特征信息。用R软件生成瀑布图，汇总具体突变信息，计算主成分分析的TMB值。应用最小绝对收缩和选择算子(Lasso)Cox回归分析从ImmPort网络中选择与TMB相关的中枢基因，建立风险评分(RS)模型评估预后价值，绘制Kaplan-Meier(K-M)曲线预测PCa患者的生存。结果表明，高TMB组的PCa患者CD8+T细胞和CD4+T细胞的浸润率明显高于低TMB组，总体生存率(OS)也高于低TMB组。抗苗勒氏激素(AMH)、杆状病毒IAP重复序列5(BIRC5)和阿片受体kappa1(OPRK1)基因是3个中枢基因，它们的拷贝数变异(CNV)相对可能影响免疫细胞的渗透。此外，AMH或BIRC5低表达的PCa患者生存期较长，复发率较低，而AMH或BIRC5高表达有利于PCa的进展。与之相比，OPRK1低表达的PCa患者早期OS较差，复发率高。综上所述，这些结果提示TMB可能是一个有前途的预测PCa预后的生物标志物，AMH、OPRK1和BIRC5是影响TMB的中枢基因，AMH、OPRK1和BIRC5可能成为PCa治疗的潜在免疫治疗靶点。
To explore the signature function of the tumor mutational burden (TMB) and potential biomarkers in prostate cancer (PCa), transcriptome profiles, somatic mutation data, and clinicopathologic feature information were downloaded from The Cancer Genome Atlas (TCGA) database. R software package was used to generate a waterfall plot to summarize the specific mutation information and calculate the TMB value of PCa. Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was used to select the hub genes related to the TMB from the ImmPort network to build a risk score (RS) model to evaluate prognostic values and plot Kaplan–Meier (K-M) curves to predict PCa patients survival. The results showed that PCa patients with a high TMB exhibited higher infiltration of CD8+ T cells and CD4+ T cells and better overall survival (OS) than those with a low TMB. The anti-Mullerian hormone (AMH), baculoviral IAP repeat-containing 5 (BIRC5), and opoid receptor kappa 1 (OPRK1) genes were three hub genes and their copy number variation (CNV) was relatively likely to affect the infiltration of immune cells. Moreover, PCa patients with low AMH or BIRC5 expression had a longer survival time and lower cancer recurrence, while elevated AMH or BIRC5 expression favored PCa progression. In contrast, PCa patients with low OPRK1 expression had poorer OS in the early stage of PCa and a higher recurrent rate than those with high expression. Taken together, these results suggest that the TMB may be a promising prognostic biomarker for PCa and that AMH, OPRK1, and BIRC5 are hub genes affecting the TMB; AMH, OPRK1, and BIRC5 could serve as potential immunotherapeutic targets for PCa treatment.
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影响因子：
9.7
作者：
Chaganty BKR;Qiu S;Gest A;Lu Y;Ivan C;Calin GA;Weiner LM;Fan Z
通讯作者：
Fan Z
影响因子：
7.3
作者：
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Abastado JP
影响因子：
9.8
作者：
Bhattacharya S;Dunn P;Thomas CG;Smith B;Schaefer H;Chen J;Hu Z;Zalocusky KA;Shankar RD;Shen-Orr SS;Thomson E;Wiser J;Butte AJ
通讯作者：
Butte AJ
肿瘤抑制因子κ阿片受体的下调预示着肝细胞癌患者的不良预后
影响因子：
3.8
作者：
Chen D;Chen Y;Yan Y;Pan J;Xing W;Li Q;Zeng W
通讯作者：
Zeng W