Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Reproductive Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Crit Rev Eukaryot Gene Expr. 2022;32(1):79-98. doi: 10.1615/CritRevEukaryotGeneExpr.2021039325.
Kidney renal clear cell carcinoma (KIRC) is the most common and aggressive subtype of renal cell carcinoma. N6-methyladenosine (m6A) RNA methylation is the most prevalent epigenetic RNA modification. Long non-coding RNAs (lncRNAs) have emerged as a key role in regulating cancer progression. However, little has been learned about the molecular functions of m6A-related lncRNAs in KIRC. The prognostic value of m6A-related ln-cRNAs was investigated in KIRC samples downloaded from The Cancer Genome Atlas (TCGA) dataset. The m6A-related lncRNAs were further screen out by Pearson correlation test. Then, 27 m6A-related lncRNAs were confirmed as potential prognostic factors through univariate Cox regression analysis. They were entered into Lasso and multivariate Cox regression to build a m6A-related lncRNA prognostic signature, including 14 m6A-related lncRNAs determined as independent prognostic factors. Additionally, a risk score calculated according to the prognostic model could divide KIRC patients into low- and high-risk groups depending on median risk score as cut-off. A prognostic nomogram, derived from the prognostic model and integrating clinical characteristics of patients, was constructed. Three distinct clusters were identified with different immune signatures through consensus clustering analysis according to the expression pattern of m6A-related lncRNAs. Twenty-seven prognostic m6A-related lncRNAs were determined as prognostic lncRNAs from TCGA-KIRC cohort. The m6A-related lncRNA prognostic signature containing 14 independent prognostic lncRNAs exhibited good accuracy in predicting overall survival of KIRC patients. We correlated the three distinct clusters with immune infiltration signature of KIRC for the first time. We found that the worse prognosis of cluster2 was probably mediated by immune evasion. In summary, our study identified a m6A-related lncRNAs prognostic signature which had great clinical value in prognosis assessment. We classified TCGA-KIRC samples into three clusters with distinct immune signatures, which could be considered as potential targets of immunotherapy for KIRC treatment in the future.
肾透明细胞癌（KIRC）是肾细胞癌中最常见和最具侵袭性的亚型。N6-甲基腺苷（m6A）RNA 甲基化是最普遍的表观遗传 RNA 修饰。长链非编码 RNA（lncRNAs）已成为调节癌症进展的关键作用。然而，对于 m6A 相关 lncRNAs 在 KIRC 中的分子功能知之甚少。本研究从癌症基因组图谱（TCGA）数据集下载的 KIRC 样本中研究了 m6A 相关 lncRNAs 的预后价值。通过 Pearson 相关检验进一步筛选 m6A 相关 lncRNAs。然后，通过单因素 Cox 回归分析进一步确认 27 个 m6A 相关 lncRNAs 为潜在的预后因素。将它们纳入 Lasso 和多因素 Cox 回归中，构建 m6A 相关 lncRNA 预后特征，包括 14 个被确定为独立预后因素的 m6A 相关 lncRNAs。此外，根据风险评分中位数将 KIRC 患者分为低风险组和高风险组。根据预后模型构建了预后列线图，该模型整合了患者的临床特征。根据 m6A 相关 lncRNAs 的表达模式，通过共识聚类分析确定了三个不同的免疫特征簇。在 TCGA-KIRC 队列中确定了 27 个预后 m6A 相关 lncRNAs 作为预后 lncRNAs。包含 14 个独立预后 lncRNAs 的 m6A 相关 lncRNA 预后特征在预测 KIRC 患者总生存方面具有良好的准确性。我们首次将三个不同的聚类与 KIRC 的免疫浸润特征相关联。我们发现，cluster2 预后较差可能是由免疫逃避介导的。总之，本研究鉴定了一个 m6A 相关 lncRNAs 预后特征，该特征在预后评估中具有重要的临床价值。我们将 TCGA-KIRC 样本分为具有不同免疫特征的三个聚类，这可能被认为是未来 KIRC 治疗免疫治疗的潜在靶点。
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