title: Upregulation of PDK1 associates with poor prognosis in esophageal squamous cell carcinoma with facilitating tumorigenicity in vitro.
abstract: 3-Phosphoinositide-dependent protein kinase-1 (PDK1) has been reported to be closely correlated with proliferation, apoptosis and invasion of esophageal cancer cells. However, its expression pattern and clinical significance in human esophageal squamous cell carcinoma (ESCC) remain unclear. To address this problem, immunohistochemistry was performed to detect the expression and the subcellular localization of PDK1 protein in 120 paired of formalin-fixed and paraffin-embedded cancerous and adjacent non-cancerous tissues. Then, its associations with tumor progression and patients' prognosis were statistically evaluated. After that, we performed migration and invasion assays of siRNA-targeted PDK1-transfected cells in vitro. As a result, immunohistochemistry analysis showed that the PDK1 protein was expressed in cytoplasm of the carcinoma cells in ESCC tissues, but not expressed in adjacent non-cancerous tissues. Statistical analysis indicated that the expression level of PDK1 protein in ESCC tissues was significantly higher than those in adjacent non-cancerous tissues (P < 0.001). In addition, high PDK1 expression was found to be closely correlated with advanced tumor stage (P = 0.006), positive lymph node metastasis (P = 0.01) and high histological grade (P = 0.02). Moreover, survival analysis revealed that PDK1 overexpression was significantly associated with shorter overall survival (P = 0.001). The multivariate analysis further identified PDK1 expression as an independent prognostic factor for ESCC patients. In ESCC cell lines, the knockdown of PDK1 using siRNA inhibited the cell migration and invasion in vitro. These findings support that PDK1 may contribute to the aggressive progression of ESCC. Of note, PDK1 may serve as an effective prognostic marker and provide a novel therapeutic strategy against human ESCC.
authors.affiliation: Department of Cardiac Surgery, The General Hospital of Shenyang Military Area Command, Shenyang, 110016, Liaoning, China.
authors.forename: Zhonglu
authors.initials: Z
authors.lastname: Yang
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Wu
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.forename: Chunhui
authors.initials: C
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Fei
authors.initials: F
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D034741:RNA, Small Interfering; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C000631429:PDK1 protein, human; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D034741:RNA, Small Interfering; D017346:Protein Serine-Threonine Kinases