ABSTRACT
Objective:To investigate the expression and related signaling pathways of reduced folate carrier 1 (RFC1) in colorectal cancer (CRC) and its relationship with the prognosis of patients.Methods:The expression of RFC1 gene in various solid tumors and CRC was analyzed in the Cancer Genome Atlas(TCGA) database. The RFC1 protein-protein interaction network was established using the search tool for the retrieval of interacting genes (STRING). The differences in survival rate between patients with high and low expression of RFC1 were compared using the Gene Expression Profile Interaction Analysis (GEPIA) database. Differentially expressed genes were subjected to Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using the Annotation, Visualization and Integrated Discovery (DAVID) database. The immunohistochemical expression level and location of RFC1 in CRC tissues and adjacent normal tissues were analyzed.Results:The expression difference of RFC1 mRNA in various human solid tumors was not obvious. In CRC tissues, the expression level of RFC1 was higher than that in adjacent normal tissues, but the expression level of RFC1 was not related to the tumor stage of the CRC patients. The correlation index between RFC1 proteins was 119, and the average inter-protein region clustering coefficient was 0.836. There was significant protein network enrichment between RFC1 and its interacting genes ( P<0.05). The biological processes of RFC1 are mainly enriched in DNA replication, semi-conservative replication to maintain telomere activity, DNA metabolism, error-free translation synthesis, DNA synthesis involved in DNA repair, etc. The cellular components are mainly enriched in replication forks, chromosomes, nucleoplasm, DNA replication factor C complex, Ctf18 RFC complex, etc. The molecular functions are mainly enriched in DNA binding nucleic acid binding, impaired DNA binding, DNA activity, catalytic activity, etc. For the KEGG signaling pathway, RFC1 is mainly enriched in DNA replication, nucleotide excision repair, mismatch repair, and malignant tumorigenesis. The disease-free survival rate and overall survival rate of CRC patients with high expression of RFC1 were lower than those of low expression group, and the difference in overall survival rate between the two was statistically significant ( P<0.05). The RFC1 protein was mainly expressed in the cytoplasm, and the positive expression was yellow-brown granular and evenly distributed in the cells. Most of the RFC1 proteins were highly or moderately expressed in colorectal cancer tissues, but low in normal intestinal epithelium. Conclusions:The expression of RFC1 is increased in CRC tissues, and its high expression is related to the decreased overall survival rate of CRC patients. RFC1 can be used as a molecular marker of poor prognosis in CRC and may become a potential target for CRC therapy.