title: Overexpression of annexin A4 indicates poor prognosis and promotes tumor metastasis of hepatocellular carcinoma.
abstract: The prognosis of hepatocellular carcinoma (HCC) after surgical resection remains unsatisfactory for the majority of HCC patients who developed early recurrence or metastasis. There is still a lack of reliable biomarkers that can be used to predict the possibility of recurrence/metastasis in HCC patients after operation. In the current study, annexin A4, a calcium-dependent phospholipid-binding protein, has been found to be significantly elevated in HCC patients with early recurrence/metastasis, and had a strong correlation with portal vein tumor thrombosis (p = 0.03) and advanced BCLC stage (p = 0.002). Cox proportional hazards regression analysis revealed that annexin A4 was an independent prognostic predictor for both early recurrence/metastasis (HR = 1.519, p = 0.032) and overall survival (HR = 1.827, p = 0.009) after surgical resection. Meanwhile, Kaplan-Meier analysis showed that Patients with high-expression levels of annexin A4 had higher recurrence rate and shorter overall survival than those with low expression (log-rank test, p < 0.001). Furthermore, in vitro studies have demonstrated that overexpression of annexin A4 facilitated HCC cell migration and invasion via regulating epithelial-mesenchymal transition (EMT). In conclusion, annexin A4 has played important roles in the progression of HCC, and might act as a potential prognostic biomarker for HCC.
authors.affiliation: Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People's Republic of China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Chen
authors.affiliation: The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Xihong Road 312, Fuzhou, 350025, Fujian Province, People's Republic of China.|The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, People's Republic of China.|Department of Pathology, School of Basic Medical Science, Fujian Medical University, Fuzhou, 350004, People's Republic of China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Chen
authors.affiliation: The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Xihong Road 312, Fuzhou, 350025, Fujian Province, People's Republic of China.|The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, People's Republic of China.
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Cai
authors.affiliation: The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Xihong Road 312, Fuzhou, 350025, Fujian Province, People's Republic of China.|The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liang
authors.affiliation: The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Xihong Road 312, Fuzhou, 350025, Fujian Province, People's Republic of China.|The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, People's Republic of China.
authors.forename: Bixing
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People's Republic of China.|The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Xihong Road 312, Fuzhou, 350025, Fujian Province, People's Republic of China.|The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, People's Republic of China.
authors.forename: Yongyi
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Xihong Road 312, Fuzhou, 350025, Fujian Province, People's Republic of China. xiaoloong.liu@gmail.com.|The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, People's Republic of China. xiaoloong.liu@gmail.com.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People's Republic of China. drjingfeng@126.com.|The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Xihong Road 312, Fuzhou, 350025, Fujian Province, People's Republic of China. drjingfeng@126.com.|The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, People's Republic of China. drjingfeng@126.com.
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Liu
mesh_terms: D017314:Annexin A4 / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D017314:Annexin A4; D014408:Biomarkers, Tumor; D012333:RNA, Messenger
keywords: Annexin A4; Early recurrences/metastasis; Epithelial–mesenchymal transition (EMT); Hepatocellular Carcinoma (HCC); Prognostic biomarker