Exploring prognostic implications of miRNA signatures and telomere maintenance genes in kidney cancer

Srinivasulu Yerukala Sathipati, Sohyun Jeong, Param Sharma, John Mayer, Rohit Sharma, Shinn-Ying Ho, Scott Hebbring
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Abstract

Kidney cancer, particularly clear cell renal cell carcinoma (KIRC), presents significant challenges in disease-specific survival. This study investigates the prognostic potential of microRNAs (miRNAs) in kidney cancers, including KIRC and kidney papillary cell carcinoma (KIRP), focusing on their interplay with telomere maintenance genes. Utilizing data from The Cancer Genome Atlas, miRNA expression profiles of 166 KIRC and 168 KIRP patients were analyzed. An evolutionary learning-based kidney survival estimator identified robust miRNA signatures predictive of 5-year survival for both cancer types. For KIRC, a 37-miRNA signature showed a correlation coefficient (R) of 0.82 and mean absolute error (MAE) of 0.65 years. Similarly, for KIRP, a 23-miRNA signature exhibited an R of 0.82 and MAE of 0.64 years, demonstrating comparable predictive accuracy. These signatures also displayed diagnostic potential with receiver operating characteristic curve values between 0.70 and 0.94. Bioinformatics analysis revealed targeting of key telomere-associated genes such as TERT, DKC1, CTC1, and RTEL1 by these miRNAs, implicating crucial pathways such as cellular senescence and proteoglycans in cancer. This study highlights the significant link between miRNAs and telomere genes in kidney cancer survival, offering insights for therapeutic targets and improved prognostic markers.
探索肾癌中 miRNA 特征和端粒维持基因对预后的影响
肾癌,尤其是透明细胞肾细胞癌(KIRC),给疾病特异性生存带来了巨大挑战。本研究调查了微RNA(miRNA)在肾癌(包括KIRC和肾乳头状细胞癌(KIRP))中的预后潜力,重点研究了它们与端粒维持基因的相互作用。利用癌症基因组图谱的数据,分析了166名KIRC和168名KIRP患者的miRNA表达谱。一种基于进化学习的肾脏存活率估算器确定了可预测两种癌症类型 5 年存活率的稳健 miRNA 特征。对于 KIRC,37 个 miRNA 标志的相关系数(R)为 0.82,平均绝对误差(MAE)为 0.65 年。同样,对于 KIRP,23 个 miRNA 标志的相关系数为 0.82,平均绝对误差为 0.64 年,显示了相当的预测准确性。这些特征还显示出诊断潜力,接收者操作特征曲线值介于 0.70 和 0.94 之间。生物信息学分析表明,这些miRNA靶向了TERT、DKC1、CTC1和RTEL1等关键端粒相关基因,这与癌症中的细胞衰老和蛋白聚糖等关键通路有关。这项研究强调了 miRNA 与端粒基因在肾癌存活过程中的重要联系,为治疗靶点和改善预后标志物提供了启示。
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