title: TNFAIP8 overexpression: a potential predictor of lymphatic metastatic recurrence in pN0 esophageal squamous cell carcinoma after Ivor Lewis esophagectomy.
abstract: Esophageal squamous cell carcinoma (ESCC) has a poor prognosis due to high lymphatic metastatic recurrence rates after Ivor Lewis esophagectomy. We sought to investigate the correlation between tumor necrosis factor alpha-induced protein 8 (TNFAIP8) expression and postoperative lymphatic recurrence in patients with pN0 ESCC. One hundred twenty-two patients with pN0 ESCC undergoing Ivor Lewis esophagectomy were enrolled in this study. TNFAIP8 overexpression was found in 73 (59.8 %) tumor specimens. The 3-year lymphatic metastatic recurrence rate among TNFAIP8-overexpressing patients was significantly higher than in TNFAIP8-negative patients (p = 0.003). Multivariate Cox regression identified TNFAIP8 overexpression as an independent risk factor for lymphatic recurrence (p = 0.048). TNFAIP8 messenger RNA (mRNA) levels were significantly higher in patients with lymphatic recurrence than in patients without tumor recurrence (p = 0.019). Stable silencing of TNFAIP8 expression in ESCC-derived cells (Eca109) reduced proliferation, motility, and invasion and induced apoptosis. In addition, transient silencing of TNFAIP8 expression decreased cell motility and invasion and increased apoptosis in a second ESCC-derived cell line (KYSE150). Taken together, these findings suggest that TNFAIP8 overexpression is a potential biomarker to identify pN0 ESCC patients at higher risk of lymphatic recurrence who may benefit from adjuvant therapy.
authors.affiliation: Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, 250021, Shandong, China.|Division of Gastroenterology, Department of Medicine and Oncology and Sidney Kimmel Comprehensive Cancer Centre, The Johns Hopkins University School of Medicine, 1503 East Jefferson Street, Room 112, Baltimore, MD, 21287, USA.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, 250021, Shandong, China.
authors.forename: Xiangyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Division of Gastroenterology, Department of Medicine and Oncology and Sidney Kimmel Comprehensive Cancer Centre, The Johns Hopkins University School of Medicine, 1503 East Jefferson Street, Room 112, Baltimore, MD, 21287, USA.
authors.forename: Jee Hoon
authors.initials: JH
authors.lastname: Song
authors.affiliation: Division of Gastroenterology, Department of Medicine and Oncology and Sidney Kimmel Comprehensive Cancer Centre, The Johns Hopkins University School of Medicine, 1503 East Jefferson Street, Room 112, Baltimore, MD, 21287, USA.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Pathology, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, 250021, Shandong, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, 250021, Shandong, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Division of Gastroenterology, Department of Medicine and Oncology and Sidney Kimmel Comprehensive Cancer Centre, The Johns Hopkins University School of Medicine, 1503 East Jefferson Street, Room 112, Baltimore, MD, 21287, USA. smeltzer@jhmi.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Meltzer
authors.affiliation: Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, 250021, Shandong, China. wz620226@hotmail.com.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000032:analysis / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D016629:Esophagectomy; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction; D016016:Proportional Hazards Models; D012307:Risk Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; C404190:TNFAIP8 protein, human
keywords: ESCC; Metastatic recurrence; RNAi; TNFAIP8; Tumor metastasis