FOXO1 Gene Downregulation and Promoter Methylation Exhibits Significant Correlation With Clinical Parameters in Indian Breast Cancer Patients

Abstract

<b>Background:</b> Forkhead box "O" one which is member of Forkhead box family of transcription factors is known to play key role in different physiological processes including cell cycle arrest, autophagy, and apoptosis. <i>FOXO1</i> is defined to play tumor suppressive role in various malignancies including breast cancer and its Dysregulation is frequently reported. However, the evaluation of <i>FOXO1</i> promoter methylation and its expression at mRNA and protein level in different stages of breast cancer and its association with different clinical parameters is still not studied. Therefore, for better understanding the role of <i>FOXO1</i> in breast cancer, in our study we examined the <i>FOXO1</i> mRNA and protein expression in Breast cancer samples of Indian breast cancer patients. <b>Results:</b> Total 127 breast cancer samples along with adjacent normal tissue (<i>n = 127</i>) were analyzed through methylation specific PCR (MS-PCR), mRNA expression (Real-time PCR) and Immunohistochemistry (IHC). We detected 69.29% cases to be downregulated at the mRNA level, and 77.95% of cases exhibited no or low protein expression. In our data we report a significant association (<i>p = 0.0001</i>) between the downregulated protein expression and promoter hypermethylation of <i>FOXO1</i> gene. We also found a significant correlation of <i>FOXO1</i> mRNA level with Age (<i>p = 0.008</i>), age at first live birth (<i>p = 0,003</i>), tumor size (<i>p = 0.05</i>) and lymph node status (<i>p = 0.01</i>). <b>Conclusion:</b> we in our study report the tumor suppressive role of <i>FOXO1</i> in case of Indian breast cancer patients and our data suggest it to exhibit prognostic importance. However, further research is needed to evaluate <i>FOXO1</i> significance in diagnostic and therapeutic targeting in breast cancer cases.