PIWI 相互作用 RNA 通路基因：透明细胞肾细胞癌的潜在生物标志物。

PIWI-Interacting RNA Pathway Genes: Potential Biomarkers for Clear Cell Renal Cell Carcinoma.

机构信息

Yingde Center, Institute of Kidney Surgery, Jinan University, Guangdong, China.

Postdoctoral Mobile Station, The First Clinical Medical College of Jinan University, Guangzhou, China.

出版信息

Dis Markers. 2022 Mar 1;2022:3480377. doi: 10.1155/2022/3480377. eCollection 2022.

DOI:10.1155/2022/3480377

PMID:35273654

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8904100/

Abstract

BACKGROUND

Clear cell renal cell carcinoma (ccRCC) is one of the most lethal malignancies in the urinary system, yet effective diagnostic and prognostic markers are lacking. Recently, several of piRNA pathway genes have been reported to be associated with cancer diagnosis and prognosis, but their role in ccRCC is still unclear.

METHODS

We analysed the expression of 27 piRNA pathway genes in 539 kidney renal clear cell carcinoma (KIRC) and 72 nontumor tissue samples (data from TCGA), and 12 mRNAs were significantly different. The aim was to sift the piRNA pathway genes that are correlated with ccRCC patient survival and to construct a piRNA pathway gene risk prognostic model using Kaplan-Meier survival curve and ROC curve, respectively.

RESULTS

5 piRNA pathway genes (TDRD7, GPAT2, PLD6, SUV39H1, and DOM3Z) were picked out and used to construct the piRNA pathway gene risk model. Kaplan-Meier survival curve analysis showed that compared with that of the low-risk group of ccRCC patients, the OS of the high-risk group of ccRCC patients was significantly reduced. The predictive performance of the prognostic risk model was measured using a ROC curve, which individually showed AUC values for 1 year of 0.707, for 3 years of 0.713, and for 5 years of 0.701. Moreover, the mRNA and protein expression levels of TDRD7 were overexpressed in the ccRCC datasets (data from our cohort, TCGA, GEO, and CPTAC) and ccRCC cell lines, and the expression levels correlated with the clinicopathological characteristics in ccRCC. The Tumor Immune Estimation Resource (TIMER) showed that the mRNA expression level of TDRD7 was positively related to tumor immune infiltrating cells (TICs) in ccRCC. Mechanistically, gene set enrichment analysis (GSEA) was performed to uncover the mechanism of TDRD7 in ccRCC. In summary, the piRNA pathway genes,especially TDRD7, may be potential cancer diagnostic and prognostic biomarkers of ccRCC.

摘要

背景

透明细胞肾细胞癌（ccRCC）是泌尿系统中最致命的恶性肿瘤之一，但缺乏有效的诊断和预后标志物。最近，已有多项研究报道 piRNA 通路基因与癌症的诊断和预后相关，但它们在 ccRCC 中的作用尚不清楚。

方法

我们分析了 539 例肾透明细胞癌（KIRC）和 72 例非肿瘤组织样本（来自 TCGA 的数据）中 27 个 piRNA 通路基因的表达情况，其中 12 个 mRNA 有显著差异。目的是筛选与 ccRCC 患者生存相关的 piRNA 通路基因，并分别使用 Kaplan-Meier 生存曲线和 ROC 曲线构建 piRNA 通路基因风险预后模型。

结果

筛选出 5 个 piRNA 通路基因（TDRD7、GPAT2、PLD6、SUV39H1 和 DOM3Z），用于构建 piRNA 通路基因风险模型。Kaplan-Meier 生存曲线分析表明，与 ccRCC 患者的低风险组相比，高风险组的 OS 明显降低。ROC 曲线测量预后风险模型的预测性能，分别显示 1 年的 AUC 值为 0.707、3 年的 AUC 值为 0.713 和 5 年的 AUC 值为 0.701。此外，在 ccRCC 数据集（来自我们的队列、TCGA、GEO 和 CPTAC）和 ccRCC 细胞系中，TDRD7 的 mRNA 和蛋白表达水平均上调，且表达水平与 ccRCC 的临床病理特征相关。肿瘤免疫估计资源（TIMER）显示，ccRCC 中 TDRD7 的 mRNA 表达水平与肿瘤免疫浸润细胞（TICs）呈正相关。从机制上看，进行了基因集富集分析（GSEA）以揭示 TDRD7 在 ccRCC 中的作用机制。总之，piRNA 通路基因，尤其是 TDRD7，可能是 ccRCC 潜在的癌症诊断和预后生物标志物。