title: Downregulation of paraoxonase 3 contributes to aggressive human hepatocellular carcinoma progression and associates with poor prognosis.
abstract: Paraoxonase (PON) enzymes possess antioxidant properties and protect against cardiovascular diseases. As a member of PON family, PON3 is primarily synthesized in the liver and poorly investigated. This study aimed to examine the expression of PON3 in human hepatocellular carcinoma (HCC) and investigate the clinical significance and biological function of PON3 in HCC patients. We first analyzed PON3 expression in 50 paired HCC samples (HCC tissues vs matched para-cancerous tissues) and 160 clinical HCC specimens by using immunohistochemistry (IHC). Our results showed that the expression of PON3 was downregulated in HCC and significantly associated with tumor-node-metastasis (TNM) stage, tumor size, and tumor number. Kaplan-Meier survival and Cox regression analyses showed that PON3 was an independent prognostic factor for overall survival (OS) and time to recurrence (TTR). Finally, we aimed to reveal the biological function of PON3 in HCC growth and metastasis, and our results showed that overexpression of PON3 potently inhibited growth and metastasis of HCC. Collectively, our study demonstrated that PON3 exhibited tumor-suppressive effects toward HCC and it might serve as a novel prognostic marker in HCC.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Yuepeng
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Department of General Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Xiufen
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China.
authors.forename: Shixu
authors.initials: S
authors.lastname: Lv
authors.affiliation: Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Yongyu
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of General Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Shan
authors.affiliation: Department of Oncological Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. yljwenzhou@126.com.
authors.forename: Le-Chi
authors.initials: LC
authors.lastname: Ye
mesh_terms: D000818:Animals; D017209:Apoptosis; D043303:Aryldialkylphosphatase / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000556:secondary* / Q000601:surgery; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D043303:Aryldialkylphosphatase; C113656:PON3 protein, human
keywords: Growth; Hepatocellular carcinoma; Metastasis; Paraoxonase 3; Prognosis