A Novel M7G-Related MicroRNAs Risk Signature Predicts the Prognosis and Tumor Microenvironment of Kidney Renal Clear Cell Carcinoma

Abstract

Background: M7G modification is extremely vital for the development of many cancers, especially tumor immunity. M7G modification is a novel functional regulator of miRNA, and the researches on m7G-related miRNAs in kidney renal clear cell carcinoma (KIRC) are still insufficient. This research aims to establish a risk signature on the foundation of m7G-associated miRNAs, which can precisely forecast the prognosis of KIRC patients.Methods: Transcriptome data and clinical data used in this study come from The Cancer Genome Atlas database. Our team utilized univariable Cox, Lasso and multivariable Cox analyses to construct a m7G-associated miRNAs risk signature that can forecast the prognosis of KIRC patients. Kaplan-Meier method, time-dependent receiver operating characteristic (ROC) curve, and the independent analysis of risk signatures were employed to verify the predictability and accuracy of the risk signature. Subsequently, based on CIBERSORT, ESTIMATE and ssGSEA algorithms, we speculated the potential impact of the proposed risk signature on tumor immune microenvironment. Ultimately, by virtue of the risk signature and tumor immunity, the hub genes affecting the prognosis of KIRC patients were screened out.Results: Our team established and verified a prognostic signature comprising 7 m7G-associated miRNAs (miR-342-3p, miR-221-3p, miR-222-3p, miR-1277-3p, miR-6718-5p, miR-1251-5p, and miR-486-5p). The results of the Kaplan-Meier survival analysis revealed that the prognosis of KIRC sufferers in the high-risk group was often unsatisfactory. The accuracy of the prediction ability of the risk signature was verified by calculating the area under the ROC curve. Univariate-multivariate Cox analyses further showed that this risk signature could be utilized as an independent prognosis-related biomarker for KIRC sufferers. The results of the immune analysis revealed that remarkable diversities existed in immune status and tumor microenvironment between high-risk and low-risk groups. On the foundation of the proposed risk signature and other clinical factors, a nomogram was established to quantitatively forecast the survival of KIRC sufferers at 1, 3 and 5 years.Conclusion: Based on m7G-related miRNAs, a risk signature was successfully constructed, which could precisely forecast the prognosis of sufferers and guide personalized immunotherapy for KIRC patients.

A Novel m7G-Related Gene Signature Predicts the Prognosis of Colon Cancer

“…Based on their functions in biological processes, m7G-related genes are classified into three types: writers (methyltransferases), readers (binding proteins), and erasers (demethylases) [ 3 , 7 , 8 ]. In human beings, methyltransferase-like 1 (METTL1) and the WD repeat domain 4 (WDR4) are the most well-studied regulators of m7G, and have been reported to participate in tumor progression by regulating tumor immunity, metabolic reprogramming, and drug resistance [ 9 , 10 , 11 , 12 , 13 ].…”

M7G-related molecular subtypes can predict the prognosis and correlate with immunotherapy and chemotherapy responses in bladder cancer patients

“…Similarly, Liu et al [ 20 ] also identified the prognostic value of m7G-related lncRNAs in prostate cancer. Moreover, three studies demonstrated the prognostic value of m7G-related mRNAs, lncRNAs, and miRNAs in clear cell renal cell carcinoma [ 16 – 18 ]. Furthermore, we also assessed the prognostic value of the risk score in various subgroups.…”

“…Li et al [ 15 ] identified m7G-related clusters that could predict the prognosis of hepatocellular carcinoma patients. Furthermore, in the field of urological tumors, three studies demonstrated the prognostic value of m7G-related mRNAs, lncRNAs and miRNAs in clear cell renal cell carcinoma [ 16 – 18 ]. Meanwhile, M7G-related genes could influence the immune infiltration of prostate cancer [ 19 , 20 ].…”

Comprehensive pan-cancer analysis of N7-methylguanosine regulators: Expression features and potential implications in prognosis and immunotherapy

“…For example, METTL1, a m7G methyltransferase, its aberrant upregulation in tumors has been found to be linked to end-stage tumors and worse prognosis, and METTL1 can drive oncogenic transformation and accelerate tumor progression by promoting m7G tRNA modification (Chen et al, 2021;Ma et al, 2021;Orellana et al, 2021). Notably, recent studies have uncovered that risk models based on m7G-associated miRNA and lncRNAs have potential value in predicting tumor prognosis and immunotherapy outcomes (Hong et al, 2022;Zhang et al, 2022). However, the potential of m7G regulators to serve as predictive biomarkers of prognosis and immunotherapy response across cancers remains unclear.…”