M7G-Related lncRNAs predict prognosis and regulate the immune microenvironment in lung squamous cell carcinoma

Abstract

Background N7-Methylguanosine (m7G) and long non-coding RNAs (lncRNAs) have been widely studied in cancer and have been found to be useful for assessing tumor progression. However, the role of m7G-related lncRNAs in lung squamous cell carcinoma (LUSC) remains unclear. Thus, it is crucial to identify m7G-associated lncRNAs with definitive prognostic value. This study aimed to investigate the prognostic value, correlation with tumor mutation burden, and impact on the tumor immune microenvironment of m7G-related lncRNAs in LUSC. Methods LUSC transcriptome data and clinical data were downloaded from The Cancer Genome Atlas, and an m7G-related lncRNA-mRNA co-expression network was constructed using Pearson’s correlation analysis. Cox regression analyses were used to determine a risk model for m7G-associated lncRNAs with prognostic value. The risk signature was verified using the Kaplan–Meier method, receiver operating characteristic curve analysis, and principal component analysis. A nomogram based on risk scores and clinical characteristics was then developed. Gene set enrichment analysis was used for functional annotation to analyze the risk signature. The association among the risk signature, tumor mutational burden, and tumor-infiltrating immune cells was then analyzed. RT-qPCR was used to investigate the expression of 6 m7G-related lncRNAs in LUSC cells. The cytological function of SRP14-AS1 was verified by wound-healing assay and transwell assay. Results A total of 293 m7G-related lncRNAs were identifed, 27 candidate m7G-related lncRNAs were signifcantly associated with overall survival (OS). Six of these lncRNAs (CYP4F26P, LINC02178, MIR22HG, SRP14-AS1, TMEM99, PTCSC2) were selected for establishment of the risk model. The OS of patients in the low-risk group was higher than that of patients in the high-risk group (p < 0.001). Multivariate cox regression analysis indicated that the model could be an independent prognostic factor for LUSC (HR = 1.859; 95% CI 1.452–2.380, p < 0.001). The ROC curve analysis revealed that the AUCs for OS in the 3-, and 5-year were 0.682, 0.657, respectively. GSEA analysis revealed that the risk model was closely related to immune-related pathways. Compared with normal lung epithelial cells, four m7G-related lncRNAs were higher expressed in cancer cells and two were lower expressed, among which knockdown of SRP14-AS1 promoted the proliferation and migration of LUSC cells. Conclusion A risk model based on six m7G-related lncRNAs with prognostic value may be a promising prognostic tool in LUSC and guide individualized patient treatment.

MMP12 serves as an immune cell–related marker of disease status and prognosis in lung squamous cell carcinoma

“…Lung cancer is one of the deadliest malignancies in the world and is the primary cause of death among cancer patients ( Siegel, Miller & Jemal, 2020 ; Mridha et al., 2022 ; Adams et al., 2023 ). Lung squamous cell carcinoma (LUSC) belongs to non-small-cell lung cancer (NSCLC), and clinical statistics show that the number of patients with LUSC accounts for about 30% of patients with NSCLC ( Li et al., 2022a ; Ding et al., 2022 ; Chen et al., 2022a ; Pan et al., 2022 ). In recent years, conventional platinum-based two-drug therapy and combination chemotherapy have remained the first-line treatments for advanced LUSC.…”

A signature of five 7-methylguanosine-related genes is a prognostic marker for lung squamous cell carcinoma

“…To evaluate the changes in the immune profile according to the risk score of each patient, we enumerated the abundance of different tumor-infiltrating immune cells in the tumor mass using the whole-exome expression data ( 28 ) and found that the LSCC patients with high-risk scores had a low immune inflammatory microenvironment, which was shown by significantly lower levels of tumor-infiltrating immune cells such as T- and B-lymphocytes, dendritic cells, macrophages, and neutrophils ( Figure 7A ). After that, we obtained the enrichment scores for 13 immune-associated pathways, such as the cytotoxic activity, antigen presentation, inflammation- promoting, and interferon pathways, to compare their activities between the high- and low-risk cohorts of patients.…”

“…The immune response is important in NSCLC, especially in tobacco smoke-related carcinogenesis ( 33 , 34 ). Thus, we profiled the immune cell population and activation of immune-associated pathways in the tumor microenvironment, gene set signatures in different immune cells, and immune-associated pathways from the literature ( 28 ) and utilized the molecular signature database to explore their role in LSCC ( https://www.gsea-msigdb.org/gsea/msigdb/ ). The enrichment score of each signature for each LSCC sample was then inferred based on the RNA-sequencing data and the single-sample GSEA (ssGSEA) by using the gene set variation analysis (GSVA) R package.…”

“…Recent studies also have shown that METTL1-mediated m7G editing is important in inhibition of lung cancer cell migration ( 26 , 27 ). Thus, in this study, we assessed the expression of m7G-related genes as a gene signature, which were selected in base of the regulation role of these genes in non-small cell lung cancer ( 28 - 30 ), to predict the prognosis of LSCC patients. We present this article in accordance with the TRIPOD reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1504/rc ).…”

Molecular subgroup establishment and signature creation of lncRNAs associated with acetylation in lung adenocarcinoma

“…Appealingly, MIR22HG can affect DNA damage and breast cancer growth in recent study [ 44 , 45 ]. Intriguingly, LINC00639, CYP4F26P as well as AF131215.6 can fill the role of prognostic biomarker in many diseases [ 46 – 48 ].…”