TNFAIP8 overexpression: a potential predictor of lymphatic metastatic recurrence in pN0 esophageal squamous cell carcinoma after Ivor Lewis esophagectomy
- 189 Downloads
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.
KeywordsESCC 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
- 8.National Comprehensive Cancer Network. NCCN clinical practice guideline in oncology (NCCN guideline): Esophageal and esophagogastric junction cancers. 2015. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#site. Accessed 23 March 2015.
- 12.Patel S, Wang FH, Whiteside TL, Kasid U. Identification of seven differentially displayed transcripts in human primary and matched metastatic head and neck squamous cell carcinoma cell lines: implications in metastasis and/or radiation response. Oral Oncol. 1997;33:197–203.CrossRefPubMedGoogle Scholar
- 13.Kumar D, Whiteside TL, Kasid U. Identification of a novel tumor necrosis factor-alpha-inducible gene, SCC-S2, containing the consensus sequence of a death effector domain of fas-associated death domain-like interleukin-1 beta-converting enzyme-inhibitory protein. J Biol Chem. 2000;275:2973–8.CrossRefPubMedGoogle Scholar
- 23.Rice TW, Rusch VW, Ishwaran H, Blackstone EH. Worldwide esophageal cancer collaboration. Cancer of the esophagus and esophagogastric junction: data-driven staging for the Seventh Edition of the American Joint Committee on Cancer/International Union Against Cancer Cancer Staging Manuals. Cancer. 2010;116:3763–73.CrossRefPubMedGoogle Scholar