title: Decreased expression of PBLD correlates with poor prognosis and functions as a tumor suppressor in human hepatocellular carcinoma.
abstract: Recent accumulating genomic and proteomic data suggested that decreased expression of phenazine biosynthesis-like domain-containing protein (PBLD) was frequently involved in hepatocellular carcinoma (HCC). However, there is lack of systematical investigation focusing on its expression pattern, clinical relevance, and biological function. Here, we found that PBLD was frequently decreased in HCC tissues relative to adjacent non-tumorigenic liver tissues. This decreased expression was significantly associated with poor tumor differentiation and advanced tumor stage. Kaplan-Meier analysis further showed that recurrence-free survival and overall survival were significantly worse among patients with low PBLD expression. Moreover, multivariate analyses revealed that PBLD was an independent predictor of OS and RFS. This prognostic value of PBLD was further validated in another independent cohort. We also found PBLD inhibited HCC cell growth and invasion in vitro and tumor growth in vivo. Furthermore, forced expression of PBLD influenced multiple downstream genes related to MAPK, NF-κB, EMT, and angiogenesis signaling pathways. PBLD deletion was an independent predictor of poor prognosis in patients with HCC. Elevated PBLD expression may reduce HCC cell growth and invasion via inactivation of several tumorigenesis-related signaling pathways.
authors.affiliation: Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.|Department of Gastroenterology, Guangzhou Key Laboratory of Digestive Disease, Guangzhou First Municipal People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.|Division of Allergy and Clinical Immunology, The Johns Hopkins School of Medicine, Baltimore, MD, United States of America.
authors.forename: Xinmei
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Jietao
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Haiyun
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Guangzhou Key Laboratory of Digestive Disease, Guangzhou First Municipal People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Department of Gastroenterology, Guangzhou Key Laboratory of Digestive Disease, Guangzhou First Municipal People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Yanlei
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.|Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Zenan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Guangzhou Key Laboratory of Digestive Disease, Guangzhou First Municipal People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Guangzhou Key Laboratory of Digestive Disease, Guangzhou First Municipal People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Side
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Guangzhou Key Laboratory of Digestive Disease, Guangzhou First Municipal People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Nie
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C434327:PBLD protein, human; D011506:Proteins; D025521:Tumor Suppressor Proteins
keywords: PBLD; hepatocellular carcinoma; prognosis; tumor suppressor gene; tumorgenesis