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. 2022 Apr 13:13:871899.
doi: 10.3389/fgene.2022.871899. eCollection 2022.

N7-Methylguanosine-Related lncRNAs: Integrated Analysis Associated With Prognosis and Progression in Clear Cell Renal Cell Carcinoma

Jie Ming  1 , Chunyang Wang  1
Affiliations

N7-Methylguanosine-Related lncRNAs: Integrated Analysis Associated With Prognosis and Progression in Clear Cell Renal Cell Carcinoma

Jie Ming et al. Front Genet. .

Abstract

N7-Methylguanosine (m7G) and long non-coding RNAs (lncRNAs) have been widely reported to play an important role in cancer. However, there is little known about the relationship between m7G-related lncRNAs and clear cell renal cell carcinoma (ccRCC). To find new potential biomarkers and construct an m7G-related lncRNA prognostic signature for ccRCC, we retrieved transcriptome data and clinical data from The Cancer Genome Atlas (TCGA), and divided the entire set into train set and test set with the ratio of 1:1 randomly. The m7G-related lncRNAs were identified by Pearson correlation analysis (|coefficients| > 0.4, and p < 0.001). Then we performed the univariate Cox regression and least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct a 12 m7G-related lncRNA prognostic signature. Next, principal component analysis (PCA), the Kaplan-Meier method, time-dependent receiver operating characteristics (ROC) were made to verify and evaluate the risk signature. A nomogram based on the risk signature and clinical parameters was developed and showed high accuracy and reliability for predicting the overall survival (OS). Functional enrichment analysis (GO, KEGG and GSEA) was used to investigate the potential biological pathways. We also performed the analysis of tumor mutation burden (TMB), immunological analysis including immune scores, immune cell infiltration (ICI), immune function, tumor immune escape (TIE) and immunotherapeutic drug in our study. In conclusion, using the 12 m7G-related lncRNA risk signature as a prognostic indicator may offer us insight into the oncogenesis and treatment response prediction of ccRCC.

Keywords: N7-methylguanosine; clear cell renal cell carcinoma; lncRNA; prognosis; tumor microenvironment; tumor mutation burden.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow chart of the study.
FIGURE 2
FIGURE 2
The volcano plot of 2121 differentially expressed m7G-realted lncRNAs.
FIGURE 3
FIGURE 3
Exhibition of m7G-related lncRNAs prognostic signature in ccRCC. (A) The 10-fold cross-validation for variable selection in the LASSO model. (B) The LASSO coefficient profile of 12 m7G-related lncRNAs. (C) The Sankey diagram of m7G genes and related lncRNAs (D–F) The PCA of two risk groups in the entire set, test set and train set, respectively.
FIGURE 4
FIGURE 4
Prognosis value of the 12 m7G-related lncRNAs model in the test, train, and entire set (A–C) Exhibition of m7G-related lncRNAs model based on risk score of the test, train, and entire set, respectively, (D–F) Survival status and time of patients between two groups in the test, train, and entire set, respectively, (G–I) The heatmap of 12 m7G-realted lncRNAs between two groups in the test, train and entire set, respectively, (J–L) The survival curve of patients between two groups in the test, train and entire set, respectively, (M) Survival curves stratified by age, gender, grade, stage, T, N, or M between two groups in the entire set.
FIGURE 5
FIGURE 5
Nomogram and assessment of the risk model (A,B) Uni- Cox and multi-Cox analyses of clinical factors and risk score with OS. (C) The nomogram that integrated the risk score and clinical parameters to predict the 1-, 3-, and 5-years OS rate. (D) The calibration curves for 1-, 3-, and 5-years OS (E–G) The ROC curves for 1-, 3-, and 5-years OS rate of the test, train, and entire set, respectively, (H–J) The ROC curves for 5-years OS rate of risk score and clinical parameters.
FIGURE 6
FIGURE 6
Functional enrichment for differentially expressed m7G genes between two groups (A) The top 30 significant terms of GO functional enrichment. BP biological process, CC cellular component, MF molecular function. (B) The circle diagram enriched in the GO analysis. (C) The top 30 significant terms of KEGG functional enrichment. (D) The circle diagram enriched in the KEGG analysis. (E) GSEA of the top 8 pathways significantly enriched in the low-risk group.
FIGURE 7
FIGURE 7
The investigation of tumor immune factors and immunotherapy (A,B) The comparison of ESTIMATE scores and stromal scores between two groups. (C) The comparison of immune scores between two groups. (D) The violin plot for different types of immune cells between two groups. (E) The heatmap of immune cells in two groups. (F) The bar plot for different types of immune cells in each sample (G–J) The survival curves stratified by dendritic cells, mast cells, T cells follicular helper and T cells regulatory (Tregs) (K) The heatmap of different immune functions (L) The comparison of immune functions between two groups (M) The comparison of TIE between two groups (N) The immunotherapy prediction of risk groups. Note: ns = non sense. “*” represents p < 0.05; “*” p < 0.01; “***” p < 0.001.
FIGURE 8
FIGURE 8
The investigation of tumor mutation burden (TMB) (A,B) TMB in the high-risk and low-risk group, respectively. (C) The comparison of TMB between two groups (D) Correlation between TMB and risk scores (E) The survival curve stratified by TMB and risk signature.
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