Comprehensive analysis of negatively correlated miRNA-mRNA regulatory pairs associated with microsatellite instability in colorectal cancer

Article type: Research Article

Authors: Liu, Cheng^{a; 1} | Zou, Xuan^{b; 1} | Song, Guoxin^{c; 1} | Fan, Xingchen^d | Peng, Shuang^d | Zhang, Shiyu^d | Geng, Xiangnan^e | zhou, Xin^d | Wang, Tongshan^d | Cheng, Wenfang^{a; *} | Zhu, Wei^{d; *}

Affiliations: [a] Department of Gastroenterology, Jiangsu Province People’s Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, China | [b] Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China | [c] Department of Pathology, Jiangsu Province People’s Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, China | [d] Department of Oncology, Jiangsu Province People’s Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, China | [e] Department of Clinical Engineer, Jiangsu Province People’s Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, China

Correspondence: [*] Corresponding authors: Wei Zhu, Department of Oncology, Jiangsu Province People’s Hospital and Nanjing Medical University First Affiliated Hospital, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China. E-mail: [email protected]. Wenfang Cheng, Department of Gastroenterology, Jiangsu Province People’s Hospital and Nanjing Medical %****␣cbm-34-cbm210408_temp.tex␣Line␣125␣**** University First Affiliated Hospital, Nanjing, Jiangsu 210029, China. E-mail: [email protected].

Note: [1] Contributed equally.

Abstract: BACKGROUND: Several studies have demonstrated that microRNAs (miRNAs) and target mRNAs are associated with different frequencies of microsatellite instability. OBJECTIVE: The study aimed to elucidate the profiles of miRNAs and target mRNAs expression and their associations with the phenotypic hallmarks of microsatellite instability in colorectal cancers (CRC) by integrating transcriptomic, immunophenotype, methylation, mutation, and survival data. METHODS: Differentially expressed miRNAs (DEmiRNAs) and mRNAs (DEmRNAs) were screened out and then the miRNA-mRNA regulatory pairs were identified through two databases. We verified that the expression levels were detected in 40 microsatellite instable (MSI) and 40 microsatellite stable (MSS) CRC samples and used the logistic regression and the Cox regression method to evaluate the diagnostic and prognostic value of negative regulatory pairs respectively. RESULTS: The best diagnostic model that combines miR-31-5p, PLAGL2, miR-361-5p, and RAB27B, which were associated with immune microenvironment, tumor mutation burden (TMB), and overall DNA methylation, could significantly predict microsatellite instability in colon tissues. MiR-31-5p and RAB27B could also predict the overall survival of MSS CRCs. CONCLUSION: This study generated a predictive model of the combination of miRNAs and mRNAs to distinguish MSI versus MSS CRCs and elaborated their potential molecular mechanisms and biological functions.

Keywords: miRNA, miRNA-mRNA networks, microsatellite instability, colorectal cancer

DOI: 10.3233/CBM-210408

Journal: Cancer Biomarkers, vol. 34, no. 3, pp. 471-483, 2022