He Qiancheng, He Rongquan, Luo Wenqi, Gan Xuli, Ma Jie, Chen Gang, Li Ping, Lan Dong, Hu Xiaohua
Department of General Medicine, The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000, Zhejiang Province, P. R. China.
Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University Nanning 530021, Guangxi Zhuang Autonomous Region, P. R. China.
Int J Clin Exp Pathol. 2017 Dec 1;10(12):11405-11414. eCollection 2017.
The clinical significance of p90-kDa ribosomal S6 kinase (RSK) family members in lung adenocarcinoma (LUAD) is unknown. The aim of this study was to analyze genomic alterations in RSK family membersand investigate the expression and clinicopathological significance of RSK4 in LUAD tissues. Genomic calterations of RSK family, overall survival, andinteraction networks were analyzed in patients with LUAD (n=522), using data from The Cancer Genome Atlas (TCGA) database. The expression of RSK4 protein was investigated in an independent cohort of patients with LUAD (n=127) by immunohistochemistry, and relationships between RSK4 protein levels and clinicopathological parameters of LUAD were analyzed. Patients with LUAD with RSK genomic alterations had significantly better overall survival than patients without alterations (P=0.026). mRNA was overexpressed in LUAD compared with noncancerous lung tissue (P=0.013), and the diagnostic value of expression was moderate, as evaluated by a value of 0.603 for the area under the receiver operator characteristic curve (95% CI, 0.551-0.655; P=0.01). RSK4 protein levels were significantly higher in LUAD than in para-carcinoma tissue (P=0.002); moreover, RSK4 protein expression was closely associated with TNM stage (P<0.001), tumor diameter (P<0.001), lymphatic metastasis (P<0.001), and distant metastasis (P=0.003). In conclusion, alterations to RSK family members may affect tumor progression in LUAD. RSK4 is a potentially useful molecular biomarker for LAUD diagnosis and may predict disease progression in patients with this condition.
p90-kDa核糖体S6激酶(RSK)家族成员在肺腺癌(LUAD)中的临床意义尚不清楚。本研究旨在分析RSK家族成员的基因组改变,并探讨RSK4在LUAD组织中的表达及其临床病理意义。利用癌症基因组图谱(TCGA)数据库的数据,对522例LUAD患者的RSK家族基因组改变、总生存期和相互作用网络进行了分析。通过免疫组织化学方法在127例独立的LUAD患者队列中研究了RSK4蛋白的表达,并分析了RSK4蛋白水平与LUAD临床病理参数之间的关系。伴有RSK基因组改变的LUAD患者的总生存期明显优于无改变的患者(P=0.026)。与非癌性肺组织相比,LUAD中mRNA表达上调(P=0.013),其诊断价值中等,通过受试者工作特征曲线下面积值0.603评估(95%CI,0.551-0.655;P=0.01)。LUAD中RSK4蛋白水平明显高于癌旁组织(P=0.002);此外,RSK4蛋白表达与TNM分期(P<0.001)、肿瘤直径(P<0.001)、淋巴转移(P<0.001)和远处转移(P=0.003)密切相关。总之,RSK家族成员的改变可能影响LUAD的肿瘤进展。RSK4是一种潜在的用于LUAD诊断的有用分子生物标志物,可能预测该疾病患者的病情进展。