Abstract
Background: 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. FOXO1 is defined to play tumor suppressive role in various malignancies including breast cancer and its Dysregulation is frequently reported. However, the evaluation of FOXO1 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 FOXO1 in breast cancer, in our study we examined the FOXO1 mRNA and protein expression in Breast cancer samples of Indian breast cancer patients. Results: Total 127 breast cancer samples along with adjacent normal tissue (n = 127) 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 (p = 0.0001) between the downregulated protein expression and promoter hypermethylation of FOXO1 gene. We also found a significant correlation of FOXO1 mRNA level with Age (p = 0.008), age at first live birth (p = 0,003), tumor size (p = 0.05) and lymph node status (p = 0.01). Conclusion: we in our study report the tumor suppressive role of FOXO1 in case of Indian breast cancer patients and our data suggest it to exhibit prognostic importance. However, further research is needed to evaluate FOXO1 significance in diagnostic and therapeutic targeting in breast cancer cases.
Highlights
According to Global Cancer statistics 2020, there were 684,996 deaths reported due to breast malignancy and it showed the highest incidence among all cancers (Globocan 2020)
The expression of Forkhead box O 1 (FOXO1) at the mRNA level was detected in case of breast cancer and adjacent normal tissue
FOXO1 which is a member of this subfamily is the key target of insulin that inhibits its transcriptional events through nuclear exclusion (Kousteni, 2012)
Summary
According to Global Cancer statistics 2020, there were 684,996 deaths reported due to breast malignancy and it showed the highest incidence among all cancers (Globocan 2020). There is a necessity in the current time to search for more reliable molecular targets to develop a better diagnostic and therapeutic approach in the treatment of breast cancer (Chan et al, 2017; Jiang et al, 2018). Our study focuses on molecular profiling of the Forkhead box O 1 (FOXO1) gene which is a potent molecule and can exhibit promising results in the development of diagnostic and therapeutic strategies. FOXO1 is defined to play tumor suppressive role in various malignancies including breast cancer and its Dysregulation is frequently reported. The evaluation of FOXO1 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. For better understanding the role of FOXO1 in breast cancer, in our study we examined the FOXO1 mRNA and protein expression in Breast cancer samples of Indian breast cancer patients
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