School of Public Health, North China University of Science and Technology, Tangshan, People's Republic of China.
School of Public Health, Xinxiang Medical University, Xinxiang, People's Republic of China.
Physiol Genomics. 2023 Oct 1;55(10):427-439. doi: 10.1152/physiolgenomics.00149.2022. Epub 2023 Aug 14.
Lung squamous cell carcinoma (LUSC) is a non-small cell lung cancer with a poor prognosis owing to late diagnosis. New molecular markers are urgently needed to improve the diagnosis and prognosis of LUSC. 7-Methylguanosine (mG) modifications, a tRNA modification, are common in eubacteria, eukaryotes, and a few archaea. These modifications promote the turnover and stability of some mRNAs to prevent mRNA decay, improve translation efficiency, and reduce ribosomal pausing but are associated with poor survival in human cancer cells. However, expression of mG-related genes in LUSC and their association with prognosis remain unclear. In the present study, we identified nine differentially expressed genes related to prognosis by comparing the expression profiles of tumor tissues (502 LUSC reports) with normal tissues (49 adjacent nontumor lung tissue reports). The genes included six upregulated genes (, , , , , and ) and three downregulated genes (, , and ). Based on these nine genes, patients with LUSC were classified into low- and high-risk groups to analyze the trends in prognosis. We found that the nine mG-related genes play important roles in immune regulation, hormone regulation, and drug sensitivity through pathways including antigen processing and presentation, adherent plaques, extracellular matrix receptor interactions, drug metabolism of cytochrome -450, and metabolism of cytochrome -450 to xenobiotics; the functions of these genes are likely accomplished in part by mA modifications. The effect of mG-related genes on the diagnosis and prognosis of LUSC was further indicated by population analysis. Based on the differential expression of 7-methylguanosine (mG) modification-associated genes between normal and lung squamous cell carcinoma (LUSC) tissues, and considering the performance of our mG-related gene risk profiles as independent risk factors in predicting overall survival, we conclude that mG modification is closely linked to the development of LUSC. In addition, this study offers a new genetic marker for predicting the prognosis of patients with LUSC and presents a crucial theoretical foundation for future investigations on the relationship between mG modification-related genes, immunity, and drug sensitivity in LUSC.
肺鳞状细胞癌(LUSC)是一种非小细胞肺癌,由于诊断较晚,预后较差。迫切需要新的分子标志物来改善 LUSC 的诊断和预后。7-甲基鸟苷(mG)修饰是一种 tRNA 修饰,常见于真核生物、古菌和少数细菌中。这些修饰促进了一些 mRNA 的周转和稳定性,防止了 mRNA 的降解,提高了翻译效率,减少了核糖体的暂停,但与人类癌细胞的不良生存相关。然而,mG 相关基因在 LUSC 中的表达及其与预后的关系尚不清楚。在本研究中,我们通过比较肿瘤组织(502 份 LUSC 报告)和正常组织(49 份相邻非肿瘤肺组织报告)的表达谱,鉴定出 9 个与预后相关的差异表达基因。这些基因包括 6 个上调基因(、、、、和)和 3 个下调基因(、和)。基于这 9 个基因,将 LUSC 患者分为低风险组和高风险组,以分析预后趋势。我们发现,这 9 个 mG 相关基因通过抗原加工和呈递、黏着斑、细胞外基质受体相互作用、细胞色素 P450 药物代谢、细胞色素 P450 对外源化学物质的代谢等途径,在免疫调节、激素调节和药物敏感性方面发挥重要作用;这些基因的功能可能部分通过 mA 修饰来完成。人群分析进一步表明了 mG 相关基因对 LUSC 诊断和预后的影响。基于正常组织和肺鳞状细胞癌(LUSC)组织之间 mG 修饰相关基因的差异表达,以及考虑到我们的 mG 相关基因风险谱作为预测总生存期的独立危险因素的表现,我们得出结论,mG 修饰与 LUSC 的发生密切相关。此外,本研究为预测 LUSC 患者的预后提供了新的遗传标志物,并为进一步研究 mG 修饰相关基因、免疫和 LUSC 药物敏感性之间的关系提供了重要的理论基础。