Author:
Takikita Mikiko,Hu Nan,Shou Jian-zhong,Wang Quan-Hong,Giffen Carol,Taylor Philip R,Hewitt Stephen M
Abstract
Abstract
Background
Cancer of the esophagus is a deadly malignancy, and development of biomarkers that predict survival is an urgent need. The apoptotic pathways have been hypothesized as important in progression of esophageal squamous cell carcinoma (ESCC). We investigated a panel of proteins that regulate apoptosis as candidate of biomarkers of prognosis in ESCC.
Methods
Tissue microarray (TMA) including 313 surgically-resected cases of ESCC specimens was built for immunohistochemical interrogation. We evaluated seven genes in the FasL-Fas apoptotic pathway - FasL, Fas, FAS-associated death domain protein (FADD), phosphorylated-FADD, and caspase 8 and 10, and the antiapoptotic protein bcl-2. We studied pathway integrity and relations to risk and clinical factors, and determined the prognostic significance of each marker.
Results
Five markers showed strong inter-marker correlations (r ≥ 0.28, p < 0.001), including FasL, Fas, FADD, and caspases 8 and 10. FasL and FADD also showed modest correlations with one or more cancer risk factors, but none of the markers was significantly associated with either tumor stage or lymph node metastasis, the only two clinical factors that predicted survival in these ESCC cases. Multivariate-adjusted proportional hazard regression models showed no association between protein expression and risk of death for any of the seven markers examined.
Conclusion
Individual biomarkers in the apoptosis pathway do not appear to predict survival of patients with ESCC.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Reference16 articles.
1. Su H, Hu N, Shih J, Hu Y, Wang Q, Chuang E, Roth M, Wang C, Goldstein A, Ding T, et al: Gene expression analysis of esophageal squamous cell carcinoma reveals consistent molecular profiles related to a family history of upper gastrointestinal cancer. Cancer Res. 2003, 63 (14): 3872-3876.
2. Screaton R, Kiessling S, Sansom O, Millar C, Maddison K, Bird A, Clarke A, Frisch S: Fas-associated death domain protein interacts with methyl-CpG binding domain protein 4: a potential link between genome surveillance and apoptosis. Proc Natl Acad Sci USA. 2003, 100 (9): 5211-5216. 10.1073/pnas.0431215100.
3. Chen G, Bhojani M, Heaford A, Chang D, Laxman B, Thomas D, Griffin L, Yu J, Coppola J, Giordano T, et al: Phosphorylated FADD induces NF-kappaB, perturbs cell cycle, and is associated with poor outcome in lung adenocarcinomas. Proc Natl Acad Sci USA. 2005, 102 (35): 12507-12512. 10.1073/pnas.0500397102.
4. Shimada K, Matsuyoshi S, Nakamura M, Ishida E, Konishi N: Phosphorylation status of Fas-associated death domain-containing protein (FADD) is associated with prostate cancer progression. J Pathol. 2005, 206 (4): 423-432. 10.1002/path.1791.
5. Shou J, Hu N, Takikita M, Roth M, Johnson L, Giffen C, Wang Q, Wang C, Wang Y, Su H, et al: Overexpression of CDC25B and LAMC2 mRNA and protein in esophageal squamous cell carcinomas and premalignant lesions in subjects from a high-risk population in China. Cancer Epidemiol Biomarkers Prev. 2008, 17 (6): 1424-1435. 10.1158/1055-9965.EPI-06-0666.
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