Identification of RNMT as an immunotherapeutic and prognostic biomarker: From pan-cancer analysis to lung squamous cell carcinoma validation
Shuqiang Huang,
Cuiyu Tan,
Jinzhen Zheng,
Zhugu Huang,
Zhihong Li,
Ziyin Lv,
Wanru Chen,
Miaoqi Chen,
Xiaojun Yuan,
Cairong Chen,
Qiuxia Yan
Affiliations
Shuqiang Huang
Center for Reproductive Medicine, the Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, Guangdong 511518, China
Cuiyu Tan
Center for Reproductive Medicine, the Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, Guangdong 511518, China
Jinzhen Zheng
Center for Reproductive Medicine, the Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, Guangdong 511518, China
Zhugu Huang
School of Pediatrics, Guangzhou Medical University, Guangzhou, Guangdong 511436, China
Zhihong Li
Center for Reproductive Medicine, the Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, Guangdong 511518, China
Ziyin Lv
The First School of Clinical Medicine, Guangzhou Medical University, Guangzhou, Guangdong 511436, China
Wanru Chen
The Third School of Clinical Medicine, Guangzhou Medical University, Guangzhou, Guangdong 511436, China
Miaoqi Chen
Center for Reproductive Medicine, the Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, Guangdong 511518, China
Xiaojun Yuan
Center for Reproductive Medicine, the Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, Guangdong 511518, China
Cairong Chen
Center for Reproductive Medicine, the Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, Guangdong 511518, China; Guangdong Engineering Technology Research Center of Urinary Continence and Reproductive Medicine, the Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, Guangdong 511518, China; Corresponding authors at: Center for Reproductive Medicine, the Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, Guangdong 511518, China.
Qiuxia Yan
Center for Reproductive Medicine, the Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, Guangdong 511518, China; Guangdong Engineering Technology Research Center of Urinary Continence and Reproductive Medicine, the Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, Guangdong 511518, China; Corresponding authors at: Center for Reproductive Medicine, the Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, Guangdong 511518, China.
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. Conclusion: 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.
