Abstract. Heat-shock factor 1 (HSF1) is the primary regulator of the response to various stressors. A previous study showed that HSF1 expression is associated with a poor prognosis in breast cancer and hepatocellular carcinoma; however, the prognostic significance of HSF1 in esophageal squamous cell carcinoma (ESCC) is unknown. Therefore, the present study investigated the association between HSF1 expression and the clinicopathological parameters of patients, as well as the association between HSF1 expression, and heat shock protein (Hsp)27, Hsp70 and Hsp90 expression induced by HSF1, by cDNA microarray and immunohistochemistry analyses. HSF1 protein and mRNA expression were assessed in resected specimens from 270 patients with ESCC in two independent cohorts. Hsp27, Hsp70 and Hsp90 expression were also assessed in 55/270 patients. Patients with high HSF1 expression had a significantly worse OS than those with low HSF1 expression in both cohorts. In multivariate analyses, pathological T stage [hazard ratio (HR), 2.21; 95% confidence interval (CI), 1.38-3.65; P=0.0008], pathological N stage (HR, 1.73; 95% CI, 1.04-3.02; P=0.03) and HSF1 expression (HR, 2.29; 95% CI, 1.48-3.64; P=0.0002) were statistically significant independent prognostic factors. Furthermore, Hsp27 and Hsp90 expression were significantly correlated with HSF1 expression (P<0.0001), but Hsp70 expression was not (P=0.38). These results indicate that HSF1 is a prognostic factor for patients with ESCC, and that Hsp27 and Hsp90, but not Hsp70, may be the downstream targets of HSF1 in ESCC.

Poly (ADP-ribose) polymerase-1 (PARP1) plays a vital role in DNA repair and is expected to be an effective target in various malignancies. The aim of the present study was to investigate the clinical and biological significance of PARP1 expression in esophageal squamous cell carcinoma (ESCC). Immunohistochemical (IHC) staining was used to examine the association between PARP1 expression and the clinicopathological features of 86 patients with ESCC. The antitumor effect of small interfering RNA against PARP1 (siPARP1) was examined in a proliferation assay, and the mechanisms of this effect were investigated using western blot analysis and cell cycle assays. Cox multivariate analysis revealed that high expression of PARP1 in IHC staining was a statistically significant independent prognostic factor of poor overall survival (OS). The adjusted hazard ratio for OS in the group with high expression of PARP1 was 2.39 (95% confidence interval, 1.29–4.44; P=0.0051). In vitro assays showed that siPARP1 significantly decreased proliferation through G2/M arrest. Furthermore, western blot analysis showed that PARP1 was associated with the ataxia telangiectasia mutated-checkpoint kinase 2-cell division control 25c pathway. The present study suggests that PARP1 expression has a critical role in ESCC progression, and may be a clinical therapeutic target.

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