Low Complement Factor H-Related 3 (CFHR3) Expression Indicates Poor Prognosis and Immune Regulation in
Haoran Wang1, Meng He1, Zheng Zhang1
1Department of Hepatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Background:
Cholangiocarcinoma (CCA) is a cancerous tumor that leads to a high rate of morbidity and death. Complement factor H-related 3 (CFHR3) is a gene belonging to the CFHR gene family. In this study, we investigated the usefulness of CFHR3 in the diagnostic stage and CCA prognosis prediction. In the interim, we looked at its coexpressed genes and their roles. The correlation between CFHR3 and immunological infiltration was also investigated.
Methods:
The expression of the genes data and the clinical information were obtained from the databases of The Cancer Genome Atlas (TCGA) together with the Gene Expression Omnibus (GEO). The crucial gene was found to be the overlapping gene in the two databases. The area under the curve (AUC) and the Kaplan-Meier survival curve were used to describe the usefulness of the predictive prognosis of CCA patients. Univariate regression analysis and multivariate survival analysis were performed to find the independent prognosis factors. The PPI network was constructed based on the STRING database, and the coexpression approach was utilized in predicting the coexpression genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were also performed to identify the related functions. Additionally, the probable mechanism of the important gene was examined using gene set enrichment analysis (GSEA). The correlation between CFHR3 and immune infiltration was discovered using TIMER. The LncACTdb 3.0 database was used to analyze the location of CFHR3 in the cell. The cBioPortal database was used to find the mutation in CFHR3.
Results:
TCGA datasets and GEO datasets revealed an elevated expression level of CFHR3 in normal tissues as well as a lower expression level in cholangiocarcinoma tissues in the present research. The low expression level of CFHR3 was related to an unfavorable prognosis. Using CFHR3 expression in diagnosis and predicting the patient prognosis (AUC = 1.000) is valuable. Using the CFHR3 gene and a time-lapse prediction, we could estimate survival rates over 1, 2, and 3 years. The AUC values were more than 0.6(AUC = 0.808; 0.760; 0.711). Functional enrichment analysis revealed a substantial correlation between this signature and complement and coagulation cascades. The same outcomes from GSEA were achieved. We found the key gene widely exists in the nucleus, exosomes, and cytoplasm of normal cells using the LncACTdb 3.0 database. In immune regulation analysis, we identified that the expression level of CFHR3 had a positive correlation with infiltrating levels of B cells, neutrophils, and macrophages, but correlated negatively with cholangiocarcinoma cells, CD8+ T cells, and monocytes.
