title: Decreased circadian component Bmal1 predicts tumor progression and poor prognosis in human pancreatic ductal adenocarcinoma.
abstract: The circadian clock has been demonstrated playing important roles in human tumorigenic process; however, the detailed clinical implications of circadian disruption on tumors have not been well understood. In this study, we investigated the expression pattern of Bmal1, the core component of the circadian system, in human pancreatic ductal adenocarcinoma (PDA). Our immunohistochemistry analysis showed that the protein level of Bmal1 was significantly decreased in tumor tissues from 87 patients with PDA compared with adjacent non-cancerous tissues. Low Bmal1 expression was associated with the TNM/clinical stage, histological differentiation, and vascular invasion of PDA; but no significant relevance to patient age, gender, the tumor location, or the size. Furthermore, Kaplan-Meier survival analysis revealed that PDA patients with low Bmal1 expression had shorter overall survival (OS) times as well as disease-free times (DFS) compared to the patients with high Bmal1 expression. Lastly, univariate and multivariate analyses identified low Bmal1 expression as an independent prognostic factor for poor survival outcome for patients with PDA. Collectively, our present study demonstrated that the decreased expression of Bmal1 is correlated with the tumor progression and poor prognosis in human PDA, which implicated its potential to be used as a biomarker for diagnosis and prognosis of PDA.
authors.affiliation: Department of Gastroenterology, The Affiliated Wuxi Second People's Hospital of Nanjing Medical University, No 68, Zhong Shan Road, Wuxi, 214002, China. Electronic address: lwh42558@sina.com.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, The Affiliated Wuxi Second People's Hospital of Nanjing Medical University, No 68, Zhong Shan Road, Wuxi, 214002, China. Electronic address: linger3307@126.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, The Affiliated Wuxi Second People's Hospital of Nanjing Medical University, No 68, Zhong Shan Road, Wuxi, 214002, China. Electronic address: luddy8891@sina.com.
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, The Affiliated Wuxi Second People's Hospital of Nanjing Medical University, No 68, Zhong Shan Road, Wuxi, 214002, China. Electronic address: jinshimao85@sina.com.
authors.forename: Shimao
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Gastroenterology, The Affiliated Wuxi Second People's Hospital of Nanjing Medical University, No 68, Zhong Shan Road, Wuxi, 214002, China. Electronic address: yangyisha0503@126.com.
authors.forename: Yisha
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pathology, The Affiliated Wuxi Second People's Hospital of Nanjing Medical University, No 68, Zhong Shan Road, Wuxi, 214002, China. Electronic address: 13771067011@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Gastroenterology, The Affiliated Wuxi Second People's Hospital of Nanjing Medical University, No 68, Zhong Shan Road, Wuxi, 214002, China. Electronic address: gonglei0520@yahoo.com.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Gong
mesh_terms: D056930:ARNTL Transcription Factors / Q000172:deficiency*; D000368:Aged; D014408:Biomarkers, Tumor / Q000172:deficiency*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002940:Circadian Rhythm; D018450:Disease Progression; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis
chemical_list: D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; D014408:Biomarkers, Tumor
keywords: Bmal1; Circadian clock; Pancreatic ductal adenocarcinoma; Prognosis