Combining bioinformatics analysis and experiments to explore CARNS1 as a prognostic biomarker for breast cancer.

BACKGROUND

Breast cancer is a heterogeneous malignant disease, which has variation in clinical behaviors. High-throughput technologies have added important genetic alternative and biological change information for breast cancer. CARNS1 is an important ATPases. It can catalyze the synthesis of carnosine, which has antiproliferative activity in cancer. Here, we hypothesize that CARNS1 plays an essential role in the development of breast cancer.

METHODS

The expressions of CARNS1 in breast cancer were data-mined and analyzed from TCGA (the Cancer Genome Atlas) and GEO (the Gene Expression Omnibus) databases. The correlation of CARNS1 expression with clinical characteristics and the diagnostic capability of CARNS1 were assessed. Experimental studies were conducted in two cohorts (n = 60) of breast cancer patients by qRT-PCR and immunohistochemical analysis.

RESULTS

CARNS1 was significantly downregulated in breast cancer. The expression was correlated with tumor molecular and histological types, T and M stages, and vital status. Kaplan-Meier survival analysis showed that the downregulation of CARNS1 was significantly related to poor overall survival and relapse-free survival. Moreover, these scenarios have been extended to ER, PR, and HER2 positive patients. Univariate and multivariate analysis showed that CARNS1 can be considered as an independent prognostic predictor for patients with breast cancer. Experimental data supported that the protein and mRNA levels of CARNS1 in breast cancer are indeed significantly downregulated.

CONCLUSION

Our findings have demonstrated that CARNS1 acts as a tumor suppressor gene and may be an independent prognostic indicator for breast cancer patients.