Esophageal adenocarcinoma is the most rapidly increasing solid malignancy with an overall 5-year survival of only 19%. Neoadjuvant chemoradiation is standard practice in most large centers but results in a complete pathologic response in only 21%, although this subset has an improved 5-year survival. In this study, connective tissue growth factor (CTGF), which is associated with increased cell migration, tissue invasion, and angiogenesis, was evaluated for its role in chemoresistance in esophageal adenocarcinoma. CTGF was found to be overexpressed in 33.3% (5 of 15; mean 3.1-fold) of esophageal adenocarcinomas on oligonucleotide microarray relative to Barrett's metaplasia. Elevated expression of CTGF was also found in 5/5 advanced stage IV esophageal adenocarcinomas on Western blot. Overexpression of CTGF was observed in 70.6% of chemoresistant esophageal adenocarcinomas (n=17) as determined using qRT-PCR and was significantly higher compared to chemo-naïve esophageal adenocarcinomas (n=102; p<0.0005). Stable inhibition with an shRNA against CTGF in the esophageal adenocarcinoma cell line Flo, which expresses endogenous CTGF, led to a significantly increased response to the chemotherapeutic agents 5-FU (9.4-fold increase), cisplatin (5.5-fold), and etoposide (4.4-fold) at 24 hours (p<0.005). These findings suggest that CTGF may be important in mediating chemoresistance in esophageal adenocarcinoma and that inhibition of CTGF could be useful in modulating chemoresistance to current neoadjuvant regimens in esophageal adenocarcinomas overexpressing CTGF.
Citation Format: Zhuwen Wang, Lin Lin, Dafydd G. Thomas, Mark B. Orringer, Andrew C. Chang, David G. Beer, Jules Lin. Overexpression of CTGF is associated with chemoresistance in esophageal adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3379. doi:10.1158/1538-7445.AM2013-3379