In Silico Study Predicts CCDC69 as a Novel Tumour Suppressor Gene in HER2+ Breast Cancer

Abstract

Differential gene expression analysis using databases followed by overall survival (OS) analysis is currently used to identify different oncogenes and tumour suppressor genes. The present study identified coiled coiled domain containing protein 69 (CCDC69) as a tumour suppressor gene in breast cancer by differential gene expression analysis using TCGA dataset for breast adenocarcinoma (BRCA) followed by OS and relapse free survival (RFS) analysis using Kaplan Meier (KM) plotter tool. CCDC69 was observed to be down regulated in tumour of breast cancer patients in BRCA. Following OS analysis for different breast cancer sub-types, low expression of CCDC69 has been observed to be associated with poor survival in HER2+ breast cancer only. CCDC69 was also found to be down regulated in different HER2+ breast cancer cells by analysing Gene Expression Omnibus (GEO) database. Additionally, CCDC69 was found to be under expressed in single cell HER2 positive population, which is evident from the single cell expression ATLAS database. Furthermore, CCDC69 has been observed to be lowly expressed with overexpression of HER2 in breast cancer by co-expression study. The possible mechanism of CCDC69 down regulation in HER2+ breast cancer was resolved using P-SCAN tool. P-SCAN analysis suggested a group of transcription factors (TFs) among which androgen receptor (AR) has been selected as the probable TF that could play a role in CCDC69 down regulation in HER2+ breast cancer. Moreover, overexpression of AR has been observed in BRCA and HER2+ single cell population. AR has also been observed to be co-expressed positively with HER2, but negatively with CCDC69 in breast cancer. Down regulation of CCDC69 can be predicted to stabilize microtubule formation following stimulation of cell growth and cell migration leading to HER2+ breast cancer progression and metastasis.