FAM65A as a novel prognostic biomarker in human tumors reveal by a pan-cancer analysis

Abstract

Background: Family with sequence similarity 65 member A (FAM65A), also known as RIPOR1, is differentially expressed between human tumor and non-tumor tissues in kinds of cancers. In addition, it was reported that the product of FAM65A may be a biomarker for cholangiocarcinoma patients. However, there is still no evidence on the relationship between the FAM65A and different types of tumors. Our study is mainly for exploring the prognostic values of FAM65A in pan-cancer and for further discovering a potential therapeutics target.

Methods: We analyzed FAM65A expression, prognostic values, genetic alteration, protein phosphorylation, immune infiltration and enrichment analysis across different types of human malignant tumors based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Additionally, Real-Time PCR (RT-qPCR) was performed to further confirm the roles of FAM65A in the pathogenesis of colorectal cancer.

Results: We found that FAM65A expression was associated with the prognosis of multiple human tumors, especially colorectal cancer. Moreover, we also observed that FAM65A was highly expressed in colorectal cancer through RT-qPCR. We observed that decreasing phosphorylation level of the S351 locus in colon adenocarcinoma, uterine corpus endometrial carcinoma and lung adenocarcinoma. And the expression of FAM65A was positively related to cancer-associated fibroblasts (CAFs) infiltration in many tumors, such as colon adenocarcinoma. Therefore, FAM65A may be a potential prognostic biomarker of human tumors.

Keywords: FAM65A; GEO; Pan-cancer; Prognostic biomarker; RIPOR1; TCGA.

Fig. 1

The expression level of FAM65A gene in different tumors. a The expression levels of FAM65A in human tumors and corresponding normal tissues are obtained through the TIMER2. b The expression levels of FAM65A in human tumors and corresponding normal tissues are obtained through the oncomine. c The FAM65A expression violin plots in different pathological stages of BLCA, COAD, KICH, OV and THCA are obtained through the GEPIA2. *P < 0.05, **P < 0.01, ***P < 0.001

Fig. 2

Relationship between FAM65A gene expression and the prognostic values in colorectal cancer. a The FAM65A prognostic values were obtained through the GEPIA2 tool. b The FAM65A prognostic value was obtained through the Oncolnc. c The FAM65A prognostic values were obtained based on the GSE17536 cohort. d RT-qPCR

Fig. 3

Mutation feature of FAM65A in different tumors of TCGA dataset. The alteration frequency with mutation type (a) and mutation site (b) are showed

Fig. 4

Phosphorylation analysis of RIPOR1 protein in different tumors. a The phosphoprotein site (S351) is showed in the schematic diagram of the RIPOR1 protein. b The box plots of different tumors, including ovarian cancer, colon cancer, UCEC and LUAD

Fig. 5

Correlation analysis between FAM65A expression and immune infiltration. a The correlation between FAM65A expression and the immune infiltration of CAFs in different tumors is presented based on EPIC, MCPCOUNTED, XCELL and TIDE algorithms. b The scatter plot data of COAD and LUSC are presented

Fig. 6

FAM65A-related gene enrichment analysis. a The top 100 FAM65A-related genes are obtained through the GEPIA2 tool based on TCGA database and the expression correlation between FAM65A and SLC39A13, SLC12A4, PSKH1, PLA2G15 and C16ORF86 is shown. b The intersection between FAM65A correlated and co-expression genes was presented in a Venn diagram, which showed four common members, namely SORBS3, SYDE1, ATP6V0D1 and CYB5R3. c KEGG pathway analysis was conducted. d The FAM65A-binding proteins confirmed by the experimental methods are presented, using the STRING tool