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基因下调和启动子甲基化与印度乳腺癌患者的临床参数显著相关。

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

作者信息

Khan Mohammad Aasif, Massey Sheersh, Ahmad Irfan, Akhter Naseem, Habib Maria, Mustafa Saad, Deo S V S, Husain Syed Akhtar

机构信息

Human Genetics Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, India.

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.

出版信息

Front Genet. 2022 Mar 3;13:842943. doi: 10.3389/fgene.2022.842943. eCollection 2022.

Abstract

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. is defined to play tumor suppressive role in various malignancies including breast cancer and its Dysregulation is frequently reported. However, the evaluation of 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 in breast cancer, in our study we examined the mRNA and protein expression in Breast cancer samples of Indian breast cancer patients. Total 127 breast cancer samples along with adjacent normal tissue () 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 () between the downregulated protein expression and promoter hypermethylation of gene. We also found a significant correlation of mRNA level with Age (), age at first live birth (), tumor size () and lymph node status (). we in our study report the tumor suppressive role of in case of Indian breast cancer patients and our data suggest it to exhibit prognostic importance. However, further research is needed to evaluate significance in diagnostic and therapeutic targeting in breast cancer cases.

摘要

叉头框“O”1(Forkhead box "O" one)是叉头框转录因子家族的成员,已知其在包括细胞周期停滞、自噬和凋亡在内的不同生理过程中发挥关键作用。它被定义为在包括乳腺癌在内的各种恶性肿瘤中发挥肿瘤抑制作用,并且其失调情况经常被报道。然而,关于其启动子甲基化以及在乳腺癌不同阶段的mRNA和蛋白质水平表达及其与不同临床参数的关联仍未得到研究。因此,为了更好地理解其在乳腺癌中的作用,在我们的研究中,我们检测了印度乳腺癌患者乳腺癌样本中的mRNA和蛋白质表达。总共127份乳腺癌样本以及相邻正常组织通过甲基化特异性PCR(MS-PCR)、mRNA表达(实时PCR)和免疫组织化学(IHC)进行了分析。我们检测到69.29%的病例在mRNA水平下调,77.95%的病例表现出无或低蛋白表达。在我们的数据中,我们报告了下调的蛋白表达与该基因启动子高甲基化之间存在显著关联()。我们还发现其mRNA水平与年龄()、首次生育年龄()、肿瘤大小()和淋巴结状态()之间存在显著相关性。我们在研究中报告了在印度乳腺癌患者中其具有肿瘤抑制作用,并且我们的数据表明它具有预后重要性。然而,需要进一步研究来评估其在乳腺癌病例诊断和治疗靶向中的意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1793/8928723/8bd2d78d169a/fgene-13-842943-g001.jpg

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