title: Prognostic potential of microRNA-138 and its target mRNA PDK1 in sera for patients with non-small cell lung cancer.
abstract: microRNA (miR)-138 has been recognized as a potential tumor suppressor via regulating 3-phosphoinositide-dependent protein kinase-1 (PDK1) expression in non-small cell lung cancer (NSCLC) cells. The aim of this study was to investigate miR-138 and PDK1 mRNA expression in serum of NSCLC and their associations with patients' prognosis. miR-138 and PDK1 mRNA expressions in 100 NSCLCs and 100 healthy control sera were detected by quantitative real-time PCR. miR-138 expression level was significantly lower in NSCLC serum samples than in healthy control serum samples (P < 0.001), while PDK1 mRNA expression level was significantly increased in NSCLC serum samples compared to healthy control serum samples (P < 0.001). In addition, miR-138 downregulation and PDK1 upregulation were both significantly associated with advanced tumor-node-metastasis (TNM) stage (both P = 0.002) and positive lymph node metastasis (both P = 0.01) of NSCLC patients. Moreover, the overall survival of NSCLC patients with low miR-138 expression or high PDK1 mRNA expression was obviously shorter than those with high miR-138 expression or low PDK1 mRNA expression (both P < 0.001). Notably, NSCLC patients with combined miR-138 downregulation and PDK1 upregulation (miR-138-low/PDK1-high) had shortest overall survival (P < 0.001). Furthermore, multivariate analysis showed that miR-138 expression (P = 0.01), PDK1 expression (P = 0.01), and combined expression of miR-138 and PDK1 (miR-138/PDK1, P = 0.001) were all independent prognostic factors for overall survival in NSCLC patients. Deregulation of miR-138/PDK1 cascade may be implicated in carcinogenesis and cancer progression of human NSCLC. More importantly, miR-138 and PDK1 may synergistically predict patients' prognosis and their combination may represent a promising prognostic biomarker of human NSCLC.
authors: Department of Respiratory Medicine, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, 471009, Henan Province, China.
authors: Lihong
authors: L
authors: Han
authors: Guoxiu
authors: G
authors: Zhang
authors: Nali
authors: N
authors: Zhang
authors: Haiyan
authors: H
authors: Li
authors: Yanyan
authors: Y
authors: Liu
authors: Aiguo
authors: A
authors: Fu
authors: Youguang
authors: Y
authors: Zheng
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000453:epidemiology / Q000378:metabolism / Q000401:mortality; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000378:metabolism / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger; D064413:3-Phosphoinositide-Dependent Protein Kinases; C578562:PDPK1 protein, human