Abstract

Melanocortin 1 receptor (MC1R) is thought to be a marker of poor prognosis and a potential target for the treatment of melanoma. Studies have found that MC1R promotes several tumor behaviors, including cell proliferation and differentiation, pigment formation, and genome damage repair. Some single-nucleotide polymorphisms (SNPs) of MC1R are involved in the occurrence and development of melanoma. A few studies have reported a relationship between MC1R and colorectal cancer (CRC). In this research, our objective was to examine MC1R expression and MC1R SNPs and investigate their correlation with the clinicopathological features of human CRC tissues. We evaluated MC1R mRNA expression by performing bioinformatic analyses on human CRC expression datasets. We used Western blotting and RT-qPCR to compare MC1R expression in CRC tissues with that in normal tissues, and MC1R SNPs in CRC tissues were detected by PCR-direct sequencing (DS). The expression of MC1R was significantly decreased in CRC tissues compared with normal tissue, and its expression was negatively associated with P53 expression, MLH1 expression, and PMS2 expression, and high MC1R expression was significantly associated with microsatellite instability (MSI). MC1R SNPs were also associated with the clinicopathological characteristics of CRC; for example, the rs2228479 locus genotype was correlated with Ki67 status, and the rs885479 locus genotype was correlated with age and T stage. In conclusion, MC1R plays a crucial role in the progression of CRC and may be a marker of poor prognosis in CRC.

Highlights

  • Colorectal cancer (CRC) is a frequently diagnosed cancer worldwide, with high mortality rates

  • Our results showed that the expression of Melanocortin 1 receptor (MC1R) was significantly lower in CRC tissue than in normal tissue, and the expression of MC1R was significantly associated with the status of the microsatellite instability (MSI)

  • T stage, N stage, TNM stage, and MC1R expression level were significantly associated with CRC prognosis (p < 0.01) by univariate

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Summary

Introduction

Colorectal cancer (CRC) is a frequently diagnosed cancer worldwide, with high mortality rates. It is estimated that 1.15 million new cases occurred and 0.58 million patients died of CRC worldwide in 2020 [1]. B-Raf proto-oncogene (BRAF), CEA cell adhesion molecule 5(CEA), epidermal growth factor receptor (EGFR), and KRAS proto-oncogene (KRAS) are the most reliable prognostic biomarkers of CRC [2,3,4]. Phosphatidylinositol 3-kinase (PI3K), tumor protein p53 (TP53), and methyltransferase 14 (METTL14) are potential prognostic markers of CRC and can be used as markers of tumor occurrence, metastasis, survival, or recurrence [5,6,7]. Many molecules can provide guidance for the prognosis and treatment of CRC, most advanced CRC patients are currently difficult to cure, and seeking a novel biomarker for synergistic or independent diagnosis and prognosis provides a basis for new drug screening and personalized treatment.

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