Khan Mohammad Aasif, Ahmad Irfan, Aloliqi Abdulaziz A, Eisa Alaa Abdulaziz, Najm Mohammad Zeeshan, Habib Maria, Mustafa Saad, Massey Sheersh, Malik Zoya, Sunita Kumari, Pawar Jogendra Singh, Akhter Naseem, Shukla N K, Deo S V S, Husain Syed Akhtar
Human Genetics Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, India.
Department of Surgical Oncology BRA-IRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
Front Oncol. 2023 Jan 16;12:1078051. doi: 10.3389/fonc.2022.1078051. eCollection 2022.
FOXO3, a member of the FOX transcription factor family, is frequently described as being deregulated in cancer. Additionally, notable role of FOXO3 can be easily recognized in the process of ageing and survival. Even though various studies have been done to acknowledge the tumour-suppressive or oncogenic role of FOXO3 in cancer, still there exist a lack of understanding in terms of cancer prognosis and treatment. Therefore, to provide better insight, our study aims to evaluate the role and function of FOXO3 in breast cancer in Indian female patients. We examined the FOXO3 expression levels in breast cancer samples by analyzing mRNA and protein expression along with its clinicopathological parameters.
A total of 127 cases of breast cancer with equal normal cases (n=127) were assessed with methylation (MS-PCR), Immunohistochemistry (IHC), mRNA expression using Real-time PCR was analysed and 66.14% cases at mRNA level were found to be downregulated, while 81.10% of cases had little or very little protein expression. Our data state, the promoter hypermethylation of the FOXO3 gene and the downregulated protein expression are significantly correlated (p=0.0004). Additionally, we found a significant correlation between the level of FOXO3 mRNA with ER (p=0.04) and status of lymph node (p=0.01) along with this.
Data suggests the prognostic significance and the tumour-suppressive role of FOXO3 in breast cancer cases studied in India. However, there is a need for the extended research targeting FOXO3 to measure its clinical potential and develop well-defined therapeutic strategies.
FOXO3是FOX转录因子家族的成员之一，在癌症中常被描述为失调。此外，FOXO3在衰老和生存过程中的显著作用也很容易被识别。尽管已经进行了各种研究来认识FOXO3在癌症中的肿瘤抑制或致癌作用，但在癌症预后和治疗方面仍缺乏了解。因此，为了提供更好的见解，我们的研究旨在评估FOXO3在印度女性乳腺癌患者中的作用和功能。我们通过分析mRNA和蛋白质表达及其临床病理参数，检测了乳腺癌样本中FOXO3的表达水平。
共评估了127例乳腺癌病例及同等数量的正常病例（n = 127），采用甲基化（MS-PCR）、免疫组织化学（IHC）方法，并通过实时PCR分析mRNA表达，发现66.14%的病例在mRNA水平下调，而81.10%的病例蛋白质表达很少或几乎没有。我们的数据表明，FOXO3基因的启动子高甲基化与蛋白质表达下调显著相关（p = 0.0004）。此外，我们还发现FOXO3 mRNA水平与雌激素受体（p = 0.04）和淋巴结状态（p = 0.01）之间存在显著相关性。
数据表明FOXO3在印度研究的乳腺癌病例中具有预后意义和肿瘤抑制作用。然而，需要针对FOXO3进行进一步研究，以评估其临床潜力并制定明确的治疗策略。
