Maiti Guru Prasad, Ghosh Amlan, Mondal Pinaki, Ghosh Susmita, Chakraborty Jayanta, Roy Anup, Roychowdhury Susanta, Panda Chinmay Kumar
Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, India; Department of Molecular Biology and Biotechnology, University of Kalyani, Nadia, India.
Department of Biological Science, Presidency University, Kolkata, India.
Oral Surg Oral Med Oral Pathol Oral Radiol. 2015 Feb;119(2):202-12. doi: 10.1016/j.oooo.2014.09.029. Epub 2014 Oct 2.
The protein SLIT2 and its receptor ROBO1 regulate different cellular processes, such as proliferation, apoptosis, and migration. In this study our aim is to understand the alterations of these genes during development of head and neck squamous cell carcinoma (HNSCC).
First, molecular alterations of the genes were analyzed in 30 dysplastic lesions, 128 primary HNSCC samples, and 1 HNSCC cell line. Then alterations were correlated with mRNA expression (n = 22) and protein expression (n = 29). Finally, the alterations were correlated with different clinicopathologic parameters and clinical outcomes of the patients.
ROBO1 had a comparatively high frequency of deletion (28.5%-54.2%) from dysplastic lesions and subsequent clinical stages than did SLIT2 (16.6-27%). On the contrary, SLIT2 had a high frequency (56.6%-81.2%) of promoter methylation from dysplastic lesions onward compared with ROBO1 (20%-32.8%). Interestingly, alterations of SLIT2 and ROBO1 were high in dysplastic lesions (80%), followed by comparable frequencies (92.5%-95.3%) in subsequent stages of tumor. Alterations of these genes showed concordance with their mRNA/protein expression and significant association with poor patient outcome.
Our data suggest that inactivation of SLIT2 and/or ROBO1 is one of the early events in development of dysplastic lesions of head and neck and has prognostic importance.
蛋白质SLIT2及其受体ROBO1调节不同的细胞过程，如增殖、凋亡和迁移。在本研究中，我们的目的是了解这些基因在头颈部鳞状细胞癌（HNSCC）发生发展过程中的变化。
首先，分析30例发育异常病变、128例原发性HNSCC样本和1株HNSCC细胞系中这些基因的分子变化。然后将这些变化与mRNA表达（n = 22）和蛋白质表达（n = 29）进行关联分析。最后，将这些变化与患者的不同临床病理参数和临床结局进行关联分析。
与SLIT2（16.6%-27%）相比，ROBO1在发育异常病变及后续临床分期中的缺失频率相对较高（28.5%-54.2%）。相反，与ROBO1（20%-32.8%）相比，SLIT2从发育异常病变开始就有较高的启动子甲基化频率（56.6%-81.2%）。有趣的是，SLIT2和ROBO1在发育异常病变中的变化率较高（80%），在肿瘤后续阶段的变化率相当（92.5%-95.3%）。这些基因的变化与其mRNA/蛋白质表达一致，且与患者预后不良显著相关。
我们的数据表明，SLIT2和/或ROBO1的失活是头颈部发育异常病变发生发展的早期事件之一，具有预后意义。
