title: Protein kinase D1 mRNA level may predict cancer-specific survival in heavy smokers with esophageal squamous cell cancers.
abstract: Protein kinase D1 (PRKD1) is a kinase that regulates various pathways, which involve in cell proliferation, apoptosis, cell adhesion and invasion. Although PRKD1 expression has been observed in many cancers, its role in esophageal squamous cell cancer (ESCC) has not been well reported. As its dysregulation in cancers is organ specific, we sought to investigate the potential role of PRKD1 in the progression of ESCC. Samples were collected from 178 patients with completely resected ESCCs at Sun Yat-sen University Cancer Center, including 47 pairs of tumorous and non-tumorous tissues. PRKD1 mRNA expression was investigated by quantitative real-time polymerase chain reaction. Receiver operating characteristic (ROC) curve analysis was used to search for a feasible cut-off point of PRKD1 mRNA levels for predicting cancer-specific survival. Kaplan-Meier and multivariate Cox regression analysis were used to assess the prognostic value of PRKD1 mRNA level in ESCC patients. In result, upregulation of PRKD1 mRNA was detected in 55.3% (26/47) of ESCC tissues compared with paired non-tumorous ones (P = 0.011). ROC analysis indicated 3.28 as a cut-off point, and thus 72 and 106 tumors with low and high PRKD1 mRNA expression were categorized. High-PRKD1 mRNA expression in tumors appeared with more frequency in heavy smokers (P = 0.002) and patients with advanced pathological T category (P = 0.034). Kaplan-Meier analysis indicated that patients with low-PRKD1 mRNA had a longer cancer-specific survival than the ones with high-PRKD1 level (P = 0.044). Multivariate analysis showed that tumorous PRKD1 mRNA expression was an independent prognostic factor (hazard ratio: 1.538, 95% confidence interval: 1.018-2.323, P = 0.041) in resected ESCC. Subgroup analysis revealed that the discernibility of PRKD1 mRNA level on ESCC outcomes was only pronounced in heavy smokers (P = 0.002), but not in non-heavy smokers (P = 0.870). PRKD1 might play a potential oncogenic role in ESCC. It might be an independent biomarker to predict prognosis in heavy smokers with ESCC.
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Research Institute, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Xie
authors.forename: S-S
authors.initials: SS
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Wen
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: K-J
authors.initials: KJ
authors.lastname: Luo
authors.forename: F
authors.initials: F
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Hu
authors.forename: J-H
authors.initials: JH
authors.lastname: Fu
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011493:Protein Kinase C / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D012907:Smoking / Q000378:metabolism* / Q000401:mortality; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C089212:protein kinase D; D011493:Protein Kinase C
keywords: esophageal cancer; outcome; protein kinase D1; smoking; tumor marker