PDF(Pubmed)
Abstract：
Clear cell renal cell carcinoma (ccRCC) is characterized by a high incidence and mortality rate. Despite advancements in therapeutic interventions, the prognosis for renal cancer patients remains suboptimal. Of late, methylation modifications have emerged as promising molecular targets for tumor assessment and treatment, yet their potential has not been fully investigated in the context of ccRCC. Transcriptomic and clinical data were extracted from The Cancer Genome Atlas, Gene Expression Omnibus, and ArrayExpress databases, leading to the identification of 57 methylation-related genes (MRGs). Utilizing DESeq2 analysis, Cox regression analysis, and the LASSO regression algorithm, a Methylation-Related Risk Score (MARS) was constructed. Cluster analysis, Gene Ontology (GO) analysis, clinical feature analysis, immune infiltration analysis, and mutation analysis were further employed to evaluate the model. Our investigation identified six pivotal prognostic MRGs and established a risk score predicated on m6A/m5C/m1A/m7G regulatory factors. This score was validated across two external cohorts and can be utilized to assess individual immune infiltration statuses and predict responses to immunotherapy. Moreover, cluster analysis delineated two distinct m6A/m5C/m1A/m7G gene clusters. We have developed and validated a robust prognostic signature based on genes associated with m6A, m5C, m1A, and m7G modifications. This gene signature demonstrates significant prognostic value in assessing survival outcomes, clinical characteristics, immune infiltration, and responses to immunotherapy in ccRCC patients. This finding provides valuable insights for refining precision treatment strategies.
摘要：
透明细胞肾细胞癌（ccRCC）的特点是发病率和死亡率高。尽管治疗干预措施取得了进展，肾癌患者的预后仍然欠佳.迟到了，甲基化修饰已成为肿瘤评估和治疗的有希望的分子靶标，然而，它们的潜力尚未在ccRCC的背景下得到充分研究。转录组和临床数据从癌症基因组图谱中提取，基因表达综合，和ArrayExpress数据库，导致57个甲基化相关基因（MRGs）的鉴定。利用DESeq2分析，Cox回归分析，和LASSO回归算法，构建甲基化相关风险评分(MARS)。聚类分析,基因本体论（GO）分析，临床特征分析,免疫浸润分析，和突变分析进一步用于评估模型。我们的调查确定了六个关键的预后MRG，并建立了基于m6A/m5C/m1A/m7G调节因子的风险评分。该评分在两个外部队列中得到验证,并且可用于评估个体免疫浸润状态和预测对免疫疗法的反应。此外，聚类分析描绘了两个不同的m6A/m5C/m1A/m7G基因簇。我们已经开发并验证了基于与m6A相关的基因的强大预后特征，m5C,m1A,和m7G修改。该基因标记在评估生存结果方面具有重要的预后价值。临床特征,免疫浸润，ccRCC患者对免疫治疗的反应。这一发现为完善精准治疗策略提供了有价值的见解。
