Tsukao Yukiko, Yamasaki Makoto, Miyazaki Yasuhiro, Makino Tomoki, Takahashi Tsuyoshi, Kurokawa Yukinori, Miyata Hiroshi, Nakajima Kiyokazu, Takiguchi Shuji, Mimori Koshi, Mori Masaki, Doki Yuichiro
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Department of Molecular and Cellular Biology, Division of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Ohita 874-0838, Japan.
Oncol Lett. 2017 Mar;13(3):1819-1825. doi: 10.3892/ol.2017.5637. Epub 2017 Jan 25.
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.
热休克因子1（HSF1）是对各种应激源反应的主要调节因子。先前的一项研究表明，HSF1表达与乳腺癌和肝细胞癌的预后不良相关；然而，HSF1在食管鳞状细胞癌（ESCC）中的预后意义尚不清楚。因此，本研究通过cDNA微阵列和免疫组织化学分析，研究了HSF1表达与患者临床病理参数之间的关系，以及HSF1表达与HSF1诱导的热休克蛋白（Hsp）27、Hsp70和Hsp90表达之间的关系。在两个独立队列中，对270例ESCC患者的切除标本进行了HSF1蛋白和mRNA表达评估。还对270例患者中的55例进行了Hsp27、Hsp70和Hsp90表达评估。在两个队列中，HSF1高表达患者的总生存期明显低于HSF1低表达患者。在多变量分析中，病理T分期[风险比（HR），2.21；95%置信区间（CI），1.38 - 3.65；P = 0.0008]、病理N分期（HR，1.73；95% CI，1.04 - 3.02；P = 0.03）和HSF1表达（HR，2.29；95% CI，1.48 - 3.64；P = 0.0002）是具有统计学意义的独立预后因素。此外，Hsp27和Hsp90表达与HSF1表达显著相关（P < 0.0001），但Hsp7O表达无相关性（P = 0.38）。这些结果表明，HSF1是ESCC患者的预后因素，并且在ESCC中，Hsp27和Hsp90而非Hsp70可能是HSF1的下游靶点。
