Lai Guichuan, Zhong Xiaoni, Liu Hui, Deng Jielian, Li Kangjie, Xie Biao
Department of Epidemiology and Health Statistics, School of Public Health, Chongqing Medical University, Yixue Road, Chongqing 400016, China.
Cancers (Basel). 2022 Oct 29;14(21):5346. doi: 10.3390/cancers14215346.
Although N7-methylguanosine (m7G) modification serves as a tumor promoter in bladder cancer (BLCA), the comprehensive role of m7G-related characterization in BLCA remains unclear. In this study, we systematically evaluated the m7G-related clusters of 760 BLCA patients through consensus unsupervised clustering analysis. Next, we investigated the underlying m7G-related genes among these m7G-related clusters. Univariate Cox and LASSO regressions were used for screening out prognostic genes and for reducing the dimension, respectively. Finally, we developed a novel m7G-related scoring system via the GSVA algorithm. The correlation between tumor microenvironment, prediction of personalized therapies and this m7G-related signature was gradually revealed. We first identified three m7G-related clusters and 1108 differentially expressed genes relevant to the three clusters. Based on the profile of 1108 genes, we divided BLCA patients into two clusters, which were quantified by our established m7G-related scoring system. Patients with higher m7G-related scores tended to have a better OS and more chances to benefit from immunotherapy. A significantly negative connection between sensitivity to classic chemotherapeutic drugs and m7G-related signature was uncovered. In summary, our data show that m7G-related characterization of BLCA patients can be of value for prognostic stratification and for patient-oriented therapeutic options, designing personalized treatment strategies in the preclinical setting.
尽管N7-甲基鸟苷（m7G）修饰在膀胱癌（BLCA）中作为肿瘤促进因子发挥作用，但m7G相关特征在BLCA中的综合作用仍不清楚。在本研究中，我们通过一致性无监督聚类分析系统评估了760例BLCA患者的m7G相关聚类。接下来，我们研究了这些m7G相关聚类中潜在的m7G相关基因。单变量Cox回归和LASSO回归分别用于筛选预后基因和降维。最后，我们通过GSVA算法开发了一种新的m7G相关评分系统。肿瘤微环境、个性化治疗预测与这种m7G相关特征之间的相关性逐渐显现。我们首先鉴定出三个m7G相关聚类以及与这三个聚类相关的1108个差异表达基因。基于1108个基因的特征，我们将BLCA患者分为两个聚类，这两个聚类通过我们建立的m7G相关评分系统进行量化。m7G相关评分较高的患者往往具有更好的总生存期，并且更有可能从免疫治疗中获益。我们还发现经典化疗药物敏感性与m7G相关特征之间存在显著的负相关。总之，我们的数据表明，BLCA患者的m7G相关特征对于预后分层以及以患者为导向的治疗选择具有价值，可在临床前环境中设计个性化治疗策略。
