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鉴定 RNMT 为免疫治疗和预后生物标志物:从泛癌分析到肺鳞癌验证。

Identification of RNMT as an immunotherapeutic and prognostic biomarker: From pan-cancer analysis to lung squamous cell carcinoma validation.

机构信息

Center for Reproductive Medicine, the Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, Guangdong 511518, China.

School of Pediatrics, Guangzhou Medical University, Guangzhou, Guangdong 511436, China.

出版信息

Immunobiology. 2024 Sep;229(5):152836. doi: 10.1016/j.imbio.2024.152836. Epub 2024 Jul 16.

DOI:10.1016/j.imbio.2024.152836
PMID:39018675
Abstract

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.

摘要

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 在泛癌中的详细作用仍不清楚。

方法

从癌症基因组图谱(TCGA)、基因-组织表达(GTEx)和癌症细胞系百科全书(CCLE)数据库中获得泛癌的批量转录组数据。分别在肿瘤免疫单细胞集线器 2(TISCH2)和临床蛋白质组肿瘤分析联盟(CPTAC)数据库中分析肺鳞状细胞癌(LUSC)的单细胞转录组和蛋白质组数据。通过 Cox 比例风险回归和 Kaplan-Meier 分析分析 RNMT 表达与癌症预后的相关性。分析 RNMT 表达与常见免疫调节剂、肿瘤突变负担(TMB)、微卫星不稳定性(MSI)、错配修复(MMR)和 DNA 甲基转移酶(DNMT)的相关性。此外,还评估了 RNMT 表达与免疫浸润水平的相关性。总共使用 1287 种机器学习组合构建 LUSC 的预后模型。qRT-PCR 和 Western blot 用于验证 LUSC 中 RNMT 上调的生物信息学发现。

结果

RNMT 在不同癌症中广泛表达,与肾嫌色细胞癌(KICH)(p=0.0033,HR=7.12)、肝肝细胞癌(LIHC)(p=0.01,HR=1.41)等癌症的预后显著相关。值得注意的是,RNMT 参与了肿瘤微环境的调节。RNMT 表达与免疫细胞表达呈正相关(Spearman 秩相关,p<0.05)。此外,在大多数癌症类型中,RNMT 表达与免疫调节剂、TMB、MSI、MMR 和 DNMT 密切相关。值得注意的是,RNMT 表达在 LUSC 中具有出色的预后和免疫表现。RNMT 的表达主要富集在 LUSC 组织的 B 细胞中。qRT-PCR 和 Western blot 验证了 LUSC 中 RNMT 的高表达。

结论

RNMT 的表达与各种肿瘤的预后和免疫浸润广泛相关,特别是 LUSC。RNMT 的检测可能为未来的肿瘤免疫研究和治疗策略提供新的思路。

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