TNFAIP8 overexpression: a potential predictor of lymphatic metastatic recurrence in pN0 esophageal squamous cell carcinoma after Ivor Lewis esophagectomy

• Published in: Tumor biology Vol. 37; no. 8; pp. 10923 - 10934
• Main Authors: Sun, Zhenguo, Liu, Xiangyan, Song, Jee Hoon, Cheng, Yulan, Liu, Yu, Jia, Yang, Meltzer, Stephen J., Wang, Zhou
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.08.2016; Springer Nature B.V
• Subjects: Adult; Aged; Apoptosis Regulatory Proteins - analysis; Apoptosis Regulatory Proteins - biosynthesis; Biomarkers, Tumor - analysis; Biomedical and Life Sciences; Biomedicine; Blotting, Western; Cancer Research; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Esophageal cancer; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - pathology; Esophageal Squamous Cell Carcinoma; Esophagectomy; Female; Gene Knockdown Techniques; Humans; Immunohistochemistry; Lymphatic Metastasis - pathology; Lymphoma; Male; Metastasis; Middle Aged; Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - pathology; Original Article; Polymerase Chain Reaction; Proportional Hazards Models; Ribonucleic acid; Risk Factors; RNA; TNFAIP8; RNAi; Metastatic recurrence; ESCC; Tumor metastasis
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-016-4978-1

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.