Ahmed Malik W, Kayani Mahmood A, Shabbir Ghulam, Ali Syed M, Shinwari Wajih-Ud-Din, Mahjabeen Ishrat
Cancer Genetics Lab, Department of Biosciences, COMSATS Institute of Information Technology, Islamabad - Pakistan.
Department of Plastic and Reconstructive Surgery, Pakistan Institute of Medical Sciences (PIMS), Islamabad - Pakistan.
Int J Biol Markers. 2016 May 28;31(2):e193-203. doi: 10.5301/jbm.5000196.
PTEN is part of large family of tyrosine phosphatases and has been found inactivated in a wide variety of human cancers.
In the present study we have tried to determine the association of the expression patterns of this gene with carcinogenesis.
First, a systematic review was carried out to ascertain the importance of the PTEN gene and its role in carcinogenesis. In the second phase, a case-control study was designed using different expression analysis techniques. Expression of PTEN mRNA was analyzed using reverse transcriptase polymerase chain reaction (RT-PCR).
Significantly downregulated expression of PTEN was observed in patients with head and neck cancer (HNC) compared to adjacent normal-tissue controls. These results were confirmed with quantitative polymerase chain reaction (qPCR). Significant downregulation of the gene was observed in HNC patients compared to adjacent normal-tissue controls. PTEN expression was correlated with different histopathological parameters of the study cohort by Spearman's correlation coefficient and a significant negative correlation was observed with pT stage (r = -0.271*; p<0.02) and grade (r = -0.228*; p<0.02) of HNC tissues. Furthermore, the expression variations of PTEN were correlated with the expression pattern of the proliferation marker Ki-67. Significantly (p<0.008) upregulated expression of Ki-67 was observed in HNC patients compared with adjacent normal-tissue controls This upregulation of Ki-67 was confirmed at the protein level by immunohistochemistry in HNC patients. When Spearman's correlation was carried out a significant negative correlation was observed between PTEN and Ki-67 (r = -0.230*; p<0.03).
Our data suggest that downregulation of PTEN and overexpression of Ki-67 may contribute to the initiation and progression of HNC.
PTEN是酪氨酸磷酸酶大家族的一部分,已发现在多种人类癌症中失活。
在本研究中,我们试图确定该基因的表达模式与致癌作用之间的关联。
首先,进行了一项系统综述,以确定PTEN基因的重要性及其在致癌作用中的作用。在第二阶段,设计了一项病例对照研究,使用不同的表达分析技术。使用逆转录聚合酶链反应(RT-PCR)分析PTEN mRNA的表达。
与相邻正常组织对照相比,头颈部癌(HNC)患者中PTEN的表达明显下调。这些结果通过定量聚合酶链反应(qPCR)得到证实。与相邻正常组织对照相比,HNC患者中该基因明显下调。通过Spearman相关系数,PTEN表达与研究队列的不同组织病理学参数相关,并且与HNC组织的pT分期(r = -0.271*;p<0.02)和分级(r = -0.228*;p<0.02)观察到显著负相关。此外,PTEN的表达变化与增殖标志物Ki-67的表达模式相关。与相邻正常组织对照相比,HNC患者中Ki-67的表达明显上调(p<0.008)。HNC患者中Ki-67的这种上调在蛋白质水平通过免疫组织化学得到证实。当进行Spearman相关性分析时,PTEN与Ki-67之间观察到显著负相关(r = -0.230*;p<0.03)。
我们的数据表明,PTEN的下调和Ki-67的过表达可能有助于HNC的发生和发展。