Higher heat shock factor 1 expression in tumor stroma predicts poor prognosis in esophageal squamous cell carcinoma patients

Yuehua Liao, Ying Xue, Lin Zhang, Xinwei Feng, Wanli Liu, Ge Zhang

Heat shock factor 1 (HSF1) is a powerful, multifaceted modifier of carcinogenesis. However, the clinical significance and biologic function of HSF1 in esophageal squamous cell carcinoma (ESCC) remain unknown. HSF1 was detected in ESCC cell lines, fibroblast cell lines and ESCC xenograft tumors and human ESCC tissues by real-time RT-PCR and western blotting. HSF1 protein expression was analyzed by immunochemistry in 134 ESCC patients followed by correlation with clinicopathological parameters. HSF1 expression is weak in fibroblast cell 3T3 and moderate in ESCC cell Eca109, but increasing expression of HSF1 was observed in both of 3T3 and Eca109 cells when they interplayed with each other. In Eca109 xenograft tumors, both tumor cells and stromal fibroblasts showed stronger expression of HSF1. In ESCC patients, the HSF1 expression in tumor or in stromal cells was significantly associated with tumor stage, lymph node metastasis and clinical stage. Multivariate analysis demonstrated a significant negative correlation between disease-free survival (DFS), overall survival (OS) and the HSF1 expression in stromal cells (P < 0.05) but not in tumor cells. Additionally, the expression of HSF1 in tumor cells or stromal cells was an independent factor for DFS (P = 0.032 or P = 0.012) and OS (P = 0.017 or P = 0.013) in metastatic ESCC patients but not for locoregional ESCC. ESCC patients with low HSF1 in both tumor cells and stromal cells had the longest survivals (P < 0.001). The interaction of tumor cells and stromal fibroblasts increases the expression of HSF1 reciprocally in tumor microenvironment. The HSF1 expression in stromal cells was significantly associated with poor prognosis of ESCC.