背景:RNA鸟嘌呤-7甲基转移酶(RNMT)的失调在肿瘤进展和免疫反应中起着至关重要的作用。然而,RNMT在泛癌症中的具体作用尚不清楚.
方法:泛癌症的大量转录组数据来自癌症基因组图谱(TCGA),基因型-组织表达(GTEx),和癌细胞系百科全书(CCLE)数据库。肺鳞状细胞癌(LUSC)的单细胞转录组和蛋白质组学数据在肿瘤免疫单细胞中心2(TISCR2)和临床蛋白质组学肿瘤分析联盟(CPTAC)数据库中进行分析,分别。通过Cox比例风险回归和Kaplan-Meier分析分析RNMT表达与癌症预后之间的相关性。RNMT表达与常见免疫调节剂的相关性,肿瘤突变负荷(TMB),微卫星不稳定性(MSI),失配修复(MMR),分析DNA甲基转移酶(DNMT)。此外,评价RNMT表达与免疫浸润水平的相关性。总共使用1287种机器学习组合来构建LUSC的预后模型。qRT-PCR和Westernblot用于验证RNMT在LUSC中上调的生物信息学发现。
结果:RNMT在不同的癌症中广泛表达,与肾脏发色团(KICH)等癌症的预后显着相关(p=0.0033,HR=7.12),肝细胞癌(LIHC)(p=0.01,HR=1.41),和其他人。值得注意的是,RNMT参与肿瘤微环境的调节。RNMT表达与免疫细胞表达呈正相关(Spearman'srankcorrelation,p<0.05)。此外,RNMT表达与免疫调节剂密切相关,TMB,MSI,MMR,和DNMT在大多数癌症类型中。值得注意的是,RNMT表达在LUSC中显示出优异的预后和免疫学表现。RNMT的表达主要富集在LUSC组织的B细胞中。qRT-PCR和Westernblot证实RNMT在LUSC中的高表达。
结论:RNMT的表达与多种肿瘤的预后和免疫浸润密切相关,尤其是LUSC。RNMT检测可能为未来肿瘤免疫研究和治疗策略提供新的思路。
BACKGROUND: Dysregulation of RNA guanine-7 methyltransferase (RNMT) plays a crucial role in the tumor progression and immune responses. However, the detailed role of RNMT in pan-cancer is still unknown.
METHODS: Bulk transcriptomic data of pan-cancer were obtained from the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases. Single-cell transcriptomic and proteomics data of lung squamous cell carcinoma (
LUSC) were analyzed in the Tumor Immune Single-cell Hub 2 (TISCH2) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases, respectively. The correlation between RNMT expression and cancer prognosis was analyzed by Cox proportional hazards regression and Kaplan-Meier analyses. The correlation of RNMT expression with common immunoregulators, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and DNA methyltransferase (DNMT) was analyzed. Additionally, the correlation between RNMT expression and immune infiltration level was evaluated. A total of 1287 machine learning combinations were used to construct prognostic models for
LUSC. qRT-PCR and Western blot were used to validate the bioinformatics findings of RNMT upregulation in
LUSC.
RESULTS: RNMT was widely expressed across different cancers, with significant correlation to prognosis in cancers such as kidney chromophobe (KICH) (p = 0.0033, HR = 7.12), liver hepatocellular carcinoma (LIHC) (p = 0.01, HR = 1.41), and others. Notably, RNMT participates in the regulation of the tumor microenvironment. RNMT expression positively correlated with immune cell expression (Spearman\'s rank correlation, p < 0.05). Moreover, RNMT expression was strongly associated with immunoregulators, TMB, MSI, MMR, and DNMT in most cancer types. Notably, RNMT expression displayed excellent prognostic and immunological performance in
LUSC. The expression of RNMT was mainly enriched in B cells of LUSC tissues. qRT-PCR and Western blot verified the high expression of RNMT in
LUSC.
CONCLUSIONS: RNMT expression widely correlated with prognosis and immune infiltration in various tumors, especially LUSC. The RNMT detection may provide a new idea for future tumor immune studies and treatment strategies.