Overexpression of MYBL2 Predicts Worse Prognosis in Clear Cell Renal Cell Carcinoma

背景：最近的研究表明，V-Myb禽成髓细胞病病毒致癌基因同源物类似物2 (MYBL2)在癌症的发生和发展中起着重要作用。鉴别有助于早期发现和危险分层的生物标志物为患有透明细胞肾细胞癌(ccRCC)的患者提供了显著的益处。本研究的目的是确定MYBL2是否可以用作ccRCC预后的预测指标。方法：根据癌症基因组图谱(TCGA)数据库，比较ccRCC组织和正常组织中MYBL2的表达。通过生存分析，临床相关性分析和列线图评估MYBL2的预测价值。通过癌症药物敏感性基因组学(GDSC)数据库鉴定了有效的ccRCC肿瘤抑制剂。进行基因集富集分析(GSEA)进行功能分析，并通过CIBERSORT算法评估ccRCC中21种浸润免疫细胞的比例。结果：MYBL2在ccRCC中的表达高于正常组织。MYBL2低表达组的患者的预后要好于MYBL2高表达组的患者。多因素Cox回归分析表明，MYBL2是ccRCC的独立预后因素。还构建了具有临床特征和MYBL2的预后列线图。基于GDSC数据库，发现一些药物对具有MYBL2表达的ccRCC细胞具有选择性抑制作用。GSEA和CIBERSORT算法的结果表明，MYBL2高表达组富集了包括免疫相关途径在内的多种途径，而11种浸润的免疫细胞与MYBL2的表达相关。结论：我们的研究表明，MYBL2可以作为ccRCC的预后标志物，并可能通过影响各种免疫细胞的浸润水平来调节免疫微环境。Background: Recent studies have revealed the significant role of V-Myb avian myeloblastosis viral oncogene homolog-like 2 (MYBL2) in the development and progression of cancer. The identification of biomarkers that contribute to early detection and risk stratification provides significant benefits for patients with clear cell renal cell carcinoma (ccRCC). The aim of the current study was to determine whether MYBL2 can be used as a predictor of the prognosis of ccRCC. Methods: Based on The Cancer Genome Atlas (TCGA) database, we compared the expression of MYBL2 in ccRCC tissues with that in normal tissues. The predictive value of MYBL2 was assessed by survival analysis, clinical correlation analysis and nomogram. Effective tumor inhibitors of ccRCC were identified by Genomics of Drug Sensitivity in Cancer (GDSC) database. Gene Set Enrichment Analysis (GSEA) was carried out for functional analysis, and the proportion of 21 kinds of infiltrating immune cells in ccRCC was evaluated by the CIBERSORT algorithm. Results: The expression of MYBL2 in ccRCC is higher than that in normal tissues. Patients in the MYBL2 low expression group had a better prognosis than those in the MYBL2 high expression group. Multivariate Cox regression analysis showed that MYBL2 was an independent prognostic factor for ccRCC. The prognostic nomogram with clinical features and MYBL2 was also constructed. Based on the GDSC database, some drugs have selective inhibitory effects on ccRCC cells with MYBL2 expression. The results of GSEA and CIBERSORT algorithm showed that multiple pathways, including immune-related pathways, were enriched in the MYBL2 high expression group, and eleven kinds of immunocytes infiltrated were correlated with the expression of MYBL2. Conclusions: Our study shows that MYBL2 can be used as a prognostic marker of ccRCC and might regulate the immune microenvironment by affecting the infiltration level of various kinds of immune cells.