Identification of m7G-Related miRNA Signatures Associated with Prognosis, Oxidative Stress, and Immune Landscape in Lung Adenocarcinoma

Abstract

The role of N7-methylguanosine(m7G)-related miRNAs in lung adenocarcinoma (LUAD) remains unclear. We used LUAD data from The Cancer Genome Atlas (TCGA) to establish a risk model based on the m7G-related miRNAs, and divided patients into high-risk or low-risk subgroups. A nomogram for predicting overall survival (OS) was then constructed based on the independent risk factors. In addition, we performed a functional enrichment analysis and defined the oxidative stress-related genes, immune landscape as well as a drug response profile in the high-risk and low-risk subgroups. This study incorporated 28 m7G-related miRNAs into the risk model. The data showed a significant difference in the OS between the high-risk and low-risk subgroups. The receiver operating characteristic curve (ROC) predicted that the area under the curve (AUC) of one-year, three-year and five-year OS was 0.781, 0.804 and 0.853, respectively. The C-index of the prognostic nomogram for predicting OS was 0.739. We then analyzed the oxidative stress-related genes and immune landscape in the high-risk and low-risk subgroups. The data demonstrated significant differences in the expression of albumin (ALB), estimated score, immune score, stromal score, immune cell infiltration and functions between the high-risk and low-risk subgroups. In addition, the drug response analysis showed that low-risk subgroups may be more sensitive to tyrosine kinase inhibitor (TKI) and histone deacetylase (HDAC) inhibitors. We successfully developed a novel risk model based on m7G-related miRNAs in this study. The model can predict clinical prognosis and guide therapeutic regimens in patients with LUAD. Our data also provided new insights into the molecular mechanisms of m7G in LUAD.

M7G-related tumor immunity: novel insights of RNA modification and potential therapeutic targets

“…Upon stimulation by antigens, B cells undergo activation and subsequently differentiate into two distinct cell types: memory B cells and plasma cells. Memory B cells accumulation was negatively correlated with m7G levels in GC, HCC and bladder cancer, while LUAD patients appeared opposite results 104 , 107 - 109 . Plasma cells are effector cells differentiated from activated B cells which produce antibodies.…”

“…In the risk models based on m7G-related genes, researchers utilized the ESTIMATE algorithm to assess stromal scores, thereby evaluating the function of stromal cells in TIME. The results showed higher stromal scores in high-risk subgroups of patients with HCC, GC and ESCC, while SKM and LUAD patients represented opposite outcomes 104 , 116 , 145 , 151 , 152 . These findings indicated diverse activation and accumulation of stromal cells in diverse cancers.…”

“…For example, a negative correlation was observed between the infiltration of naïve B cells and the risk score for an unfavorable prognosis in CRC and LUAD. However, clustering analysis in cutaneous melanoma indicated a higher level of naïve B cell infiltration in the high-risk group 104 - 106 .…”

N7-methylguanosine-related miRNAs predict hepatocellular carcinoma prognosis and immune therapy

“…A necroptotic miRNA-based signature can predict colon cancer patients’ overall survival rate [ 24 ]. Furthermore, m 7 G-miRNA-based signatures have been reported in tumor research [ 25 ]. For instance, Hong et al constructed a risk model including seven m 7 G-miRNAs in kidney renal clear cell carcinoma that could be used to predict patient prognosis and personalize immunotherapy [ 26 ].…”