Abstract
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). RSK4 mRNA was overexpressed in LUAD compared with noncancerous lung tissue (P=0.013), and the diagnostic value of RSK4 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.