Hypermethylated LATS2 gene with decreased expression in female breast cancer: A case control study from North India.

Abstract Background LATS2 , a presumed tumor suppressor gene located on chromosome 13q11–12 is involved in cell growth related activity like regulation of cell cycle at G1/S. The reduced expression of LATS2 has been reported in many tumors; including tumors of Breast, which is to the best of our knowledge has not been studied in north Indian female breast cancer population. Objective Here, we looked upon the expression pattern and methylation status of the LATS2 gene in north Indian female breast cancer cases to further strengthen its role as a tumor suppressor gene and more importantly as a cancer biomarker. Methods mRNA expression level was determined by real time PCR in 140 Breast cancer patients, Protein expression was studied by Immunohistochemistry and Promoter methylation was studied by Methylation specific PCR. All findings were correlated with clinicopathological features. Results LATS2 mRNA expression was remarkably downregulated in 67.85% (95/140) cases. The expression of Large Associated Tumor Suppressor 2 at protein level was also absent in 67.85% (95/140) cases. The absence of LATS2 protein strongly correlated with promoter hypermethylation where 91 out of a total of 107 hyper methylated cases showed absence of protein (91/107, 85%). The absence of LATS2 protein was strongly significant with HER2 neu status (0.01), TNM staging (0.009) and Molecular subtype (0.024). Conclusion The decreased expression in breast cancer seems to be associated with hypermethylation of LATS2 promoter regions. Further LATS2 as a tumor suppressor can be recognized as a promising Biomarker in Breast cancer pathogenesis. Though, further studies, targeting larger sets of breast cancer population are required to establish LATS2 as a promising biomarker. Highlights • Expression and Methylation status of LATS2 gene was studied in 140 Breast cancer cases. • The promoter was hypermethylated and expression was downregulated at mRNA and Protein level. • Multiparametric analysis showed high association between methylation, expression and clinical parameters of patients. • LATS2 may serve as potential biomarker, at least in Breast cancer. [ABSTRACT FROM AUTHOR]