Decreased expression of PBLD correlates with poor prognosis and functions as a tumor suppressor in human hepatocellular carcinoma
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Aimin Li1,2,*, Qun Yan1,*, Xinmei Zhao1,3,*, Jietao Zhong1, Haiyun Yang1, Zhiqiang Feng2, Yanlei Du2, Yadong Wang1, Zenan Wang1,4, Hong Wang2, Yongjian Zhou2, Side Liu1 and Yuqiang Nie2
1 Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
2 Department of Gastroenterology, Guangzhou Key Laboratory of Digestive Disease, Guangzhou First Municipal People’s Hospital, Guangzhou Medical University, Guangzhou, China
3 Division of Allergy and Clinical Immunology, The Johns Hopkins School of Medicine, Baltimore, MD, United States of America
4 Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
* These authors have contributed equally to this work
Yuqiang Nie, email:
Side Liu, email:
Keywords: hepatocellular carcinoma, tumorgenesis, PBLD, tumor suppressor gene, prognosis
Received: May 31, 2015 Accepted: November 14, 2015 Published: November 22, 2015
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.
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