An innovative model based on N7-methylguanosine-related lncRNAs for forecasting prognosis and tumor immune landscape in bladder cancer

Abstract

Background As a novel type of the prevalent post-transcriptional modifications, N7-methylguanosine (m7G) modification is essential in the tumorigenesis, progression, and invasion of many cancers, including bladder cancer (BCa). However, the integrated roles of m7G-related lncRNAs in BCa remain undiscovered. This study aims to develop a prognostic model based on the m7G-related lncRNAs and explore its predictive value of the prognosis and anti-cancer treatment sensitivity. Methods We obtained RNA-seq data and corresponding clinicopathological information from the TCGA database and collected m7G-related genes from previous studies and GSEA. Based on LASSO and Cox regression analysis, we developed a m7G prognostic model. The Kaplan–Meier (K-M) survival analysis and ROC curves were performed to evaluate the predictive power of the model. Gene set enrichment analysis (GSEA) was conducted to explore the molecular mechanisms behind apparent discrepancies between the low- and high-risk groups. We also investigated immune cell infiltration, TIDE score, TMB, the sensitivity of common chemotherapy drugs, and the response to immunotherapy between the two risk groups. Finally, we validated the expression levels of these ten m7G-related lncRNAs in BCa cell lines by qRT-PCR. Results We developed a m7G prognostic model (risk score) composed of 10 m7G-related lncRNAs that are significantly associated with the OS of BCa patients. The K-M survival curves revealed that the high-risk group patients had significantly worse OS than those in the low-risk group. The Cox regression analysis confirmed that the risk score was a significant independent prognostic factor for BCa patients. We found that the high-risk group had higher the immune scores and immune cell infiltration. Furthermore, the results of the sensitivity of common anti-BCa drugs showed that the high-risk group was more sensitive to neoadjuvant cisplatin-based chemotherapy and anti-PD1 immunotherapy. Finally, qRT-PCR revealed that AC006058.1, AC073133.2, LINC00677, and LINC01338 were significantly downregulated in BCa cell lines, while the expression levels of AC124312.2 and AL158209.1 were significantly upregulated in BCa cell lines compared with normal cell lines. Conclusion The m7G prognostic model can be applied to accurately predict the prognosis and provide robust directions for clinicians to develop better individual-based and precise treatment strategies for BCa patients.

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

“…PPI network showed that FN1 and ITGB1 were the core genes in regulating m7G 125 . Similar mechanisms were demonstrated in breast cancers and bladder cancers 127 , 132 . However, it was reported in LUAD and cutaneous melanoma that neutrophils were less infiltrated in group of high m7G levels 56 , 133 .…”

“…The prognostic models of ovarian cancers, CRC, HCC and HNSCC based on m7G regulators indicated more recruitment of M1 macrophages in low-risk group of patients 85 , 96 , 115 , 126 . However, contradictory outcomes were observed in bladder cancers 107 , 127 . In addition, as precursor cells of macrophages, monocytes infiltration was reported to be negative correlated with m7G levels in CRC, bladder cancers and prostate cancers 89 , 127 , 128 .…”

“…However, contradictory outcomes were observed in bladder cancers 107 , 127 . In addition, as precursor cells of macrophages, monocytes infiltration was reported to be negative correlated with m7G levels in CRC, bladder cancers and prostate cancers 89 , 127 , 128 . These results are consistent with the role of monocytes in mononuclear phagocyte system.…”

Disulfideptosis-associated lncRNAs reveal features of prognostic, immune escape, tumor mutation, and tumor malignant progression in renal clear cell carcinoma

“…WWC2-AS2 has been identified as an immune-related lncRNA in cervical cancer [28]. LINC01338 is a member of N7-methylguanosine-related lncRNAs in bladder cancer [29], It can also be used to accurately predict the prognosis of bladder cancer patients, providing strong guidance for clinicians in developing better-individualized precision treatment strategies. TIDE (http://tide.dfci.harvard.edu/) stands for tumor immune dysfunction and rejection.…”

Identification and Validation of eRNA as a Prognostic Indicator for Cervical Cancer

“…In order to investigate how changes in eRNA expression influence prognosis, it is essential to compare the functional and signaling pathway differences between the high-risk and low-risk subgroups, which are grouped based on the 8-eRNA model [22]. We conducted a differential expression analysis between these two groups (Figure S1a,b) and identified 141 genes that were differentially expressed using the GSEA analysis thresholds of |log2FC| ≥ 1.5 and p < 0.05 (Table S5).…”