The Role of RNA Methylation Modification Related Genes in Prognosis and Immunotherapy of Colorectal Cancer

Abstract

Background

Researches showed RNA methylation genes can affect the prognosis of tumors. Thus, the study aimed to comprehensively analyze the effects of RNA methylation regulatory genes in prognosis and treatment of colorectal cancer (CRC).

Methods

Prognostic signature associated with CRCs were constructed by differential expression analysis, Cox and Least Absolute Shrinkage and Selection Operator (LASSO) analyses. Receiver operating characteristic (ROC) and Kaplan–Meier survival analyses were used to validate the reliability of the developed model. Gene Ontology (GO), Gene set variation analysis (GSVA), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed for functional annotation. Finally, normal and cancerous tissue were collected to validate gene by quantitative real-time PCR (qRT-PCR).

Results

A prognostic risk model based on leucine rich pentatricopeptide repeat containing (LRPPRC) and ubiquitin-like with PHD and ring finger domains 2 (UHRF2) was constructed and relevant to the overall survival (OS) of CRC. Functional enrichment analysis revealed that collagen fibrous tissue, ion channel complex and other pathways were significantly enriched, which might help explain the underlying molecular mechanisms. There were significant differences in ImmuneScore, StromalScore, ESTIMATEScore between high- and low-risk groups (p < 0.05). Ultimately, qRT-PCR validation showed that a significant upregulation in the expression of LRPPRC and UHRF2 in cancerous tissue, which verified the effectiveness of our signature.

Conclusion

In conclusion, 2 prognostic genes (LRPPRC and UHRF2) related to RNA methylation were identified by bioinformatics analysis, which might supply a new insight into the treatment and evaluation of CRC.

Keywords:

• colorectal cancer
• prognosis
• RNA methylation regulatory genes
• tumor microenvironment
• immunotherapy

Abbreviations

CRC, colorectal cancer; CNV, copy number variation; TCGA, The Cancer Genome Atlas; OS, overall survival; K-M, Kaplan–Meier; LASSO, Least Absolute Shrinkage and Selection Operator; ROC, Receiver operating characteristic; GO, Gene Ontology; GSVA, Gene set variation analysis; KEGG, Kyoto Encyclopedia of Genes and Genomes; qRT-PCR, quantitative real-time PCR; LRPPRC, leucine rich pentatricopeptide repeat containing; UHRF2, ubiquitin-like with PHD and ring finger domains 2; m6A, N⁶-methyladenosine; m5C, N⁵-methylcytosine; m1A, N¹-methyladenosine; m7G, N⁷-methylguanosine; METTL3, methyltransferase-like 3; GLUT1, glucose transporter 1; mTORC1, mechanistic target of rapamycin complex 1; BP, biological process; NSUN5, NOP2/Sun RNA methyltransferase 5; SNV, single nucleotide variation; GEO, Gene Expression Omnibus; DEGs, differentially expressed genes; BP, biological process; MF, molecular function; TMB, tumor mutational Burden; PPR, pentatricopeptide repeat; MAP1S, microtubule-associated protein 1 family; SNHG17, SnoRNA Host Gene 17; TME, Tumor immune microenvironment; TAMs, macrophages; EMT, epithelial-mesenchymal transformation; ICB, Immune checkpoint blocking.

Ethics Statement

This study was approved by Ethics Committee in Clinical Research of the First Affiliated Hospital of Wenzhou Medical University. All methods were carried out in accordance with relevant guidelines and regulations or declaration of Helsinki. Informed consent was obtained from all subjects and/or their legal guardian.

Disclosure

The authors report no conflicts of interest in this work.