Sibin M K, Bhat Dhananjaya I, Narasingarao K V L, Lavanya Ch, Chetan G K
Department of Human Genetics, National Institute of Mental Health and Neuro Sciences, Bangalore, India, 560029.
Department of Neurosurgery, National Institute of Mental Health and Neuro Sciences, Bangalore, India, 560029.
Tumour Biol. 2015 Sep;36(10):7607-14. doi: 10.1007/s13277-015-3480-5. Epub 2015 Apr 29.
Human high-grade glioma is heterogeneous in nature based on pathological and genetic profiling. Various tumour suppressor gene alterations are considered as prognostic markers in high-grade glioma. Gene expression of CDKN2A (p16) is used in various cancers as a prognostic biomarker along with methylation and deletion status of this gene. Expression levels of p16 mRNA were not studied as a biomarker in gliomas before. In this study, we have performed mRNA quantification analysis on 48 high-grade glioma tissues and checked for a possible prognostic role. The decreased expression of p16 mRNA in majority of the tumour tissues (57.1 %) was observed when compared to control tissues (P = 0.02). mRNA expression level was correlated with clinical variables also. p16 deletion status and BMI1 mRNA expression were also considered for comparison. p16 mRNA was negatively correlated with the BMI1 mRNA (P = <0.0001) but not with p16 deletion. p16 mRNA expression, midline shift in MRI and tumour type were able to predict patient survival in overall survival (OS) and progression-free survival (PFS). p16 mRNA could independently predict prognosis of OS (P = 0.0146) and PFS (P = 0.0305) in multivariate analysis. We have shown that p16 mRNA expression can act as an independent prognostic biomarker in high-grade glioma.
基于病理和基因分析,人类高级别胶质瘤本质上具有异质性。多种肿瘤抑制基因改变被视为高级别胶质瘤的预后标志物。CDKN2A(p16)的基因表达连同该基因的甲基化和缺失状态,在多种癌症中用作预后生物标志物。此前尚未研究过p16 mRNA的表达水平作为胶质瘤的生物标志物。在本研究中,我们对48例高级别胶质瘤组织进行了mRNA定量分析,并检查其可能的预后作用。与对照组织相比,在大多数肿瘤组织(57.1%)中观察到p16 mRNA表达降低(P = 0.02)。mRNA表达水平也与临床变量相关。还比较了p16缺失状态和BMI1 mRNA表达。p16 mRNA与BMI1 mRNA呈负相关(P = <0.0001),但与p16缺失无关。p16 mRNA表达、MRI中线移位和肿瘤类型能够预测总生存期(OS)和无进展生存期(PFS)患者的生存情况。在多变量分析中,p16 mRNA能够独立预测OS(P = 0.0146)和PFS(P = 0.0305)的预后。我们已经表明,p16 mRNA表达可作为高级别胶质瘤的独立预后生物标志物。