Protein Expression Profiling in Esophageal Adenocarcinoma Patients Indicates Association of Heat-Shock Protein 27 Expression and Chemotherapy Response

Abstract

Purpose: To identify pretherapeutic predictive biomarkers in tumor biopsies of patients with locally advanced esophageal adenocarcinomas treated with neoadjuvant chemotherapy, we used an explorative proteomic approach to correlate pretherapeutic protein expression profiles with tumor response to neoadjuvant chemotherapy. Experimental Design: Thirty-four patients with locally advanced esophageal adenocarcinomas who received neoadjuvant platin/5-fluorouracil^based chemotherapy before surgical resection were enrolled in this study. Response to chemotherapy was determined (a) by the amount of decline of [ between responders and nonresponders. Immunohistochemistry and gene expression analysis confirmed these data, showing a significant association between low HSP27 expression and nonresponse to neoadjuvant chemotherapy (P = 0.049 and P = 0.032, respectively). Conclusions: Albeit preliminary, our encouraging data suggest that protein expression profiling may distinguish cancers with a different response to chemotherapy. Our results suggest that response to chemotherapy may be related to a different activation of stress response and inflammatory biology in general. Moreover, the potential of HSPs and GRPs as biomarkers of chemotherapy response warrants further validation.

HSP47 is associated with the prognosis of laryngeal squamous cell carcinoma by inhibiting cell viability and invasion and promoting apoptosis

“…HSP27 has been reported to be overexpressed and associated with poor prognosis in many human cancers, including breast, rectal, gastric, lung, liver and prostate cancers (33)(34)(35)(36). Contrary to the findings in most cancers, in human esophageal squamous cell carcinoma (HESCC), the expression of HSP27 was low, and this low expression was correlated with poor prognosis (37,38).…”

Current advances in esophageal cancer proteomics

“…To identify predictive biomarkers, Langer et al analyzed pretherapeutic protein expression profiles in tumor biopsy specimens of 34 EAC patients treated with neoadjuvant chemotherapy [56]. The authors found that the levels of cellular stress response-associated Hsp27 and Hsp60, glucose-regulated proteins 94 and 78, and a number of cytoskeletal proteins differed significantly between responders and nonresponders.…”

In vitro and in vivo evaluation of tubulin inhibitors with non-small cell lung cancer pre-clinical models

“…Such protection is conferred by enhanced proliferation [11,13] and suppressed apoptosis in cancer cells [14][15][16]. Increased expression of Hsp27 is found in various cancer types [9,10,[17][18][19][20][21], supporting the hypothesis that Hsp27 is a therapeutic target in a broad spectrum of cancers. In fact, several agents that modulate Hsp27 have already exhibited promising anti-tumor activity in preclinical models of a variety of tumors, particularly those expressing high levels of Hsp27 [17,22,23].…”