Purpose: Clear cell renal cell carcinoma (ccRCC) is highly heterogeneous and is one of the most lethal types of cancer within the urinary system. Aberrant expression of 5-methylcytosine (m⁵C) RNA methylation regulators has been shown to result in occurrence and progression of tumors. However, the role of these regulators in ccRCC remains unclear.
Materials and Methods: We extracted RNA sequencing expression data with corresponding clinical information of patients with ccRCC from The Cancer Genome Atlas (TCGA) database. We then compared the expression profiles of m⁵C RNA methylation regulators between normal and ccRCC tissues, and determined different subtypes through consensus clustering analysis. In addition, we constructed a prognostic signature and evaluated it using a range of bioinformatics approaches. The expression of signature-related genes was subsequently verified in the clinical samples using qRT-PCR.
Results: We identified 12 differentially expressed m⁵C RNA methylation regulators between cancer and normal control samples. Two clusters of patients with ccRCC and diverse clinicopathological characteristics and prognoses were then determined through consensus clustering analysis. Functional annotations revealed that m⁵C RNA regulators were significantly correlated with the ccRCC progression. Moreover, we constructed a four-gene risk score signature (comprised of NOP2, NSUN4, NSUN6, and TET2) and divided the patients with ccRCC into high- and low-risk groups based on the median risk score. The risk score was associated with clinicopathological features and was an independent prognostic indicator of ccRCC. Our stratified analysis results suggest that the signature has high prognostic value. Based on qRT-PCR results, the NOP2 and NSUN4 mRNA expressions were higher and those of NSUN6 and TET2 were lower in ccRCC tissues than in normal tissues.
Conclusion: Our results demonstrate that m⁵C RNA methylation regulators may affect ccRCC progression and could be exploited for diagnostic and prognostic purposes.

Keywords: ccRCC, 5-methylcytosine RNA methylation regulators, prognostic signature, epigenetics, bioinformatics


中文翻译：

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m5C RNA甲基化调节因子相关特征对透明细胞肾细胞癌的预后价值

目的：透明细胞肾细胞癌 (ccRCC) 具有高度异质性，是泌尿系统中最致命的癌症类型之一。^{已显示 5-甲基胞嘧啶 (m 5} C) RNA 甲基化调节剂的异常表达导致肿瘤的发生和进展。然而，这些监管机构在 ccRCC 中的作用仍不清楚。
材料和方法：我们从癌症基因组图谱（TCGA）数据库中提取了 ccRCC 患者的 RNA 测序表达数据和相应的临床信息。^{然后我们比较了 m 5}的表达谱正常和ccRCC组织之间的C RNA甲基化调节因子，并通过共识聚类分析确定不同的亚型。此外，我们构建了一个预后特征，并使用一系列生物信息学方法对其进行了评估。随后使用 qRT-PCR 在临床样本中验证了特征相关基因的表达。
结果：我们在癌症和正常对照样本之间鉴定出 12 个差异表达的 m ^{5 C RNA 甲基化调节因子。}然后通过共识聚类分析确定两组具有不同临床病理特征和预后的 ccRCC 患者。功能注释显示 m ⁵C RNA 调节因子与 ccRCC 进展显着相关。此外，我们构建了一个四基因风险评分签名（由 NOP2、NSUN4、NSUN6 和 TET2 组成），并根据中位风险评分将 ccRCC 患者分为高危组和低危组。风险评分与临床病理学特征相关，是 ccRCC 的独立预后指标。我们的分层分析结果表明该特征具有很高的预后价值。根据qRT-PCR结果，与正常组织相比，ccRCC组织中NOP2和NSUN4 mRNA的表达较高，NSUN6和TET2的表达较低。
结论：我们的结果表明，m ⁵C RNA 甲基化调节剂可能会影响 ccRCC 的进展，并可用于诊断和预后目的。

关键词： ccRCC，5-甲基胞嘧啶 RNA 甲基化调节因子，预后特征，表观遗传学，生物信息学