Tumor Biology

, Volume 37, Issue 8, pp 10923–10934 | Cite as

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

  • Zhenguo Sun
  • Xiangyan Liu
  • Jee Hoon Song
  • Yulan Cheng
  • Yu Liu
  • Yang Jia
  • Stephen J. MeltzerEmail author
  • Zhou WangEmail author
Original Article


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.


ESCC TNFAIP8 Tumor metastasis Metastatic recurrence RNAi 



The authors thank the Department of Pathology, Provincial Hospital Affiliated to Shandong University, for specimen collection and staining evaluation. This work is supported by grants from the National Natural Science Foundation of China (No. 81172161), Jinan Science and Technology Plan (201202041). Dr. Meltzer is the Myerberg/Hendrix Professor of Gastroenterology and an American Cancer Society Clinical Research Professor.

Compliance with ethical standards

Conflict of interests


Supplementary material

13277_2016_4978_MOESM1_ESM.doc (566 kb)
ESM 1 (DOC 565 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Zhenguo Sun
    • 1
    • 2
  • Xiangyan Liu
    • 1
  • Jee Hoon Song
    • 2
  • Yulan Cheng
    • 2
  • Yu Liu
    • 3
  • Yang Jia
    • 1
  • Stephen J. Meltzer
    • 2
    Email author
  • Zhou Wang
    • 1
    Email author
  1. 1.Department of Thoracic SurgeryProvincial Hospital Affiliated to Shandong UniversityJinanChina
  2. 2.Division of Gastroenterology, Department of Medicine and Oncology and Sidney Kimmel Comprehensive Cancer CentreThe Johns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Department of PathologyProvincial Hospital Affiliated to Shandong UniversityJinanChina

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