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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-Sen University, No. 132 Waihuandong Road, University Town, Guangzhou, 510006, China. yuehua33@163.com.
Yuehua
Y
Liao
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-Sen University, No. 132 Waihuandong Road, University Town, Guangzhou, 510006, China. xuedongzhe@126.com.
Ying
Y
Xue
Department of Clinical Laboratory Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China. zhanglin@sysucc.org.cn.
Lin
L
Zhang
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-Sen University, No. 132 Waihuandong Road, University Town, Guangzhou, 510006, China. fxw0110@163.com.
Xinwei
X
Feng
Department of Clinical Laboratory Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China. liuwl@sysucc.org.cn.
Wanli
W
Liu
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-Sen University, No. 132 Waihuandong Road, University Town, Guangzhou, 510006, China. zhangge@mail.sysu.edu.cn.
Ge
G
Zhang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D000076249:Heat Shock Transcription Factors; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D041681:NIH 3T3 Cells; D011379:Prognosis; D017154:Stromal Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D059016:Tumor Microenvironment
D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors