Guan Bo, Ren Feng, Shan Weimin, Zhang Shangrong
Department of Urology, Fuyang People's Hospital, Fuyang, China.
Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China.
Transl Cancer Res. 2022 Mar;11(3):508-518. doi: 10.21037/tcr-22-117.
In this study, we sought to investigate the association between N6-methyladenosine (mA) RNA methylation-modification patterns and patient prognosis in clear cell renal cell carcinoma (ccRCC) and construct a ccRCC molecular signature according to expressions of mA-related genes.
First, the clinical data and the transcriptomes of 530 patients with ccRCC were downloaded from The Cancer Genome Atlas (TCGA). The expression patterns of mA-related genes were extracted, and the differences in mA-modification patterns between normal and tumor renal tissues were analyzed. To explore the prognostic role of mA-modification patterns a in ccRCC, the molecular subtypes of ccRCC were identified based on the expression patterns of the mA-related genes, and survival rates in patients with the different subtypes were compared. According to expressions of mA-related genes and clinical prognosis data, a prognostic molecular signature was constructed using least absolute shrinkage and selector operation (LASSO)-Cox regression analysis.
Among the 13 mA -related genes identified in this study, 8 (, and ) showed significant expression differences between normal and tumor renal tissues. The molecular subtypes of ccRCC identified according to their expression of the 13 mA-related genes were associated with differential clinical outcomes.
Following TCGA data-mining, different molecular subtypes of ccRCC based on mA RNA methylation patterns were found to have different prognoses. The molecular signature constructed according to the expression patterns of mA-related genes could predict patient prognosis in ccRCC. We believe mA RNA methylation modification is a potential therapeutic target and may play a crucial role in ccRCC.
在本研究中,我们试图探究N6-甲基腺嘌呤(m⁶A)RNA甲基化修饰模式与透明细胞肾细胞癌(ccRCC)患者预后之间的关联,并根据m⁶A相关基因的表达构建ccRCC分子特征。
首先,从癌症基因组图谱(TCGA)下载530例ccRCC患者的临床数据和转录组。提取m⁶A相关基因的表达模式,分析正常和肿瘤肾组织之间m⁶A修饰模式的差异。为了探究m⁶A修饰模式在ccRCC中的预后作用,基于m⁶A相关基因的表达模式确定ccRCC的分子亚型,并比较不同亚型患者的生存率。根据m⁶A相关基因的表达和临床预后数据,使用最小绝对收缩和选择算子(LASSO)-Cox回归分析构建预后分子特征。
在本研究鉴定的13个m⁶A相关基因中,8个(……)在正常和肿瘤肾组织之间表现出显著的表达差异。根据13个m⁶A相关基因的表达确定的ccRCC分子亚型与不同的临床结局相关。
通过对TCGA数据的挖掘,发现基于m⁶A RNA甲基化模式的不同ccRCC分子亚型具有不同的预后。根据m⁶A相关基因的表达模式构建的分子特征可以预测ccRCC患者的预后。我们认为m⁶A RNA甲基化修饰是一个潜在的治疗靶点,可能在ccRCC中起关键作用。