Comprehensive analysis of the expression, prognostic significance, and function of FAM83 family members in breast cancer

Abstract

Background: The FAM83 family plays a key role in tumorigenesis and cancer progression. However, the role of the FAM83 family in the development of breast tumors is unclear to date. This report explores the expression, prognostic significance, and function of the FAM83 family members in breast cancer using public databases.

Methods: UALCAN database was used to explore the expression of FAM83 family members in breast cancer. Furthermore, we validated the expression of FAM83 family members in twenty pairs of breast cancer and normal tissues by RT-PCR. Kaplan-Meier plotter database was used to explore the prognostic significance of FAM83 family members in breast cancer. GeneMANIA and DAVID databases were used for functional and pathway enrichment analysis of genes co-expressed with FAM83A, FAM83D, FAM83F, and FAM83G. MEXPRESS and UALCAN databases were used to analyze the level of DNA promoter methylation of FAM83A, FAM83D, FAM83F, and FAM83G in breast cancer. TIMER database was utilized to explore the relationships between immune cell infiltration and FAM83A, FAM83D, FAM83F, and FAM83G expression.

Results: Among FAM83 family members, FAM83A, FAM83D, FAM83F, and FAM83G were higher expressed in breast cancer than in normal tissues. We also validated the significant high expression of FAM83A, FAM83D, FAM83F, and FAM83G mRNA in breast cancer than in normal samples. Their increased expression has an adverse prognostic effect on breast cancer patients. These genes co-expressed with FAM83A, FAM83D, FAM83F, and FAM83G might take part in cell proliferation, G2/M transition of the mitotic cell cycle, regulation of apoptosis process and other cancer-related biological processes. In addition, they were mainly enriched in the Hippo signaling pathway, Hedgehog signaling pathway, PI3K/AKT signaling pathway, and other cancer-related pathways. We also found that promoter DNA methylation might regulate the expression of FAM83A, FAM83D, FAM83F, and FAM83G mRNA in most CpG islands. At last, we found the expression of FAM83A, FAM83D, FAM83F, and FAM83G mRNA was significantly related to immune cell infiltration.

Conclusions: FAM83A, FAM83D, FAM83F, and FAM83G were highly expressed in breast cancer tissues and had an adverse effect on the survival outcomes of breast cancer patients. Also, they were involved in breast cancer-related signal pathways. Therefore, they might serve as potential therapeutic targets for breast cancer clinical treatment.

Keywords: Breast cancer; FAM83 family; Therapeutic targets.

Fig. 1

Gene expression levels of the FAM83 family genes in breast cancer and normal breast tissues by UALCAN database. Expression of A FAM83A, B FAM83B, C FAM83C, D FAM83D, E FAM83E, F FAM83F, G FAM83G, and H FAM83H in breast cancer based on sample types. (The solid line in the middle represented the mean value of gene expression, and the upper and lower solid lines represented the mean value plus or minus standard deviation of gene expression. The dotted line connected the mean and standard deviation in every picture. The solid lines and dotted lines in these pictures obtained from UALCAN database meant the same in this paper)

Fig. 2

Validation of the mRNA expression of FAM83 family genes in fresh breast cancer and healthy breast tissue samples. Validation of A FAM83A, B FAM83B, C FAM83C, D FAM83D, E FAM83E, F FAM83F, G FAM83G, H FAM83H expression by RT-PCR. (The solid line in the middle represented the mean value of gene expression, and the upper and lower solid lines represented the mean value plus or minus standard deviation of gene expression. The vertical solid line connected the mean and standard deviation in every picture)

Fig. 3

The effect of the gene expression levels of the FAM83 family on the RFS of breast cancer patients. Effect of A FAM83A, B FAM83B, C FAM83C, D FAM83D, E FAM83E, F FAM83F, G FAM83G, and H FAM83H expression on the RFS of breast cancer patients

Fig. 4

The effect of the gene expression levels of the FAM83 family on the OS of breast cancer patients. Effect of A FAM83A, B FAM83B, C FAM83C, D FAM83D, E FAM83E, F FAM83F, G FAM83G, and H FAM83H expression on the OS of breast cancer patients

Fig. 5

Functional and pathway enrichment analysis of genes co-expressed with FAM83A, FAM83D, FAM83F, and FAM83G. A The genes co-expressed with FAM83A, FAM83D, FAM83F, and FAM83G. B Biological process of GO functional enrichment analysis. C Cellular components of GO functional enrichment analysis. D Molecular function of GO functional enrichment analysis. E KEGG pathway enrichment analysis of genes co-expressed with FAM83A, FAM83D, FAM83F, and FAM83G

Fig. 6

Promoter DNA methylation might regulate the expression of FAM83A, FAM83D, FAM83F, and FAM83G mRNA in most CpG islands. A–D MEXPRESS analysis. E–H UALCAN analysis

Fig. 7

The relationships between immune cell infiltration and A FAM83A, B FAM83D, C FAM83F, and D FAM83G expression by “TIMER” analysis tool