MC1R Is a Prognostic Marker and Its Expression Is Correlated with MSI in Colorectal Cancer

Curr Issues Mol Biol. 2021 Oct 11;43(3):1529-1547. doi: 10.3390/cimb43030108.

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.

Keywords: CRC; MC1R; SNPs; clinicopathologic features; prognostic marker.

MeSH terms

  • Biomarkers, Tumor*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / pathology
  • Computational Biology / methods
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immune Checkpoint Proteins / genetics
  • Immune Checkpoint Proteins / metabolism
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Microsatellite Instability*
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Protein Interaction Mapping
  • Receptor, Melanocortin, Type 1 / genetics*
  • Receptor, Melanocortin, Type 1 / metabolism
  • Transcriptome
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Workflow

Substances

  • Biomarkers, Tumor
  • Immune Checkpoint Proteins
  • MC1R protein, human
  • Receptor, Melanocortin, Type 1
  • TP53 protein, human
  • Tumor Suppressor Protein p53