热休克蛋白27（HSP27）和热休克蛋白70（HSP70）的过表达与食管腺癌患者生存率降低相关。
Overexpression of HSP27 and HSP70 is associated with decreased survival among patients with esophageal adenocarcinoma.
作者信息
Söderström Henna K, Kauppi Juha T, Oksala Niku, Paavonen Timo, Krogerus Leena, Räsänen Jari, Rantanen Tuomo
机构信息
Department of General Thoracic Surgery, Helsinki University Central Hospital, Helsinki 00029, Finland.
Faculty of Medicine and Life Sciences, University of Tampere, Tampere 33014, Finland.
出版信息
World J Clin Cases. 2019 Feb 6;7(3):260-269. doi: 10.12998/wjcc.v7.i3.260.
BACKGROUND
Overexpression of heat shock proteins (HSPs) is associated with several malignancies and contributes to the development, progression, and metastasis of cancer, in addition to the inhibition of cellular death. In recent years, there has been active research into using HSP inhibitors in several malignancies. Due to the poor prognosis of esophageal adenocarcinoma (EAC), it would be valuable to find new biomarkers for the development of cancer treatments.
AIM
To evaluate the expressions of HSP27 and HSP70 and their effect on survival in EAC.
METHODS
Immunohistochemical analyses and evaluations of HSP27 and HSP70 expression were performed on all available samples from 93 patients diagnosed with EAC between 1990 and 2007 at two university hospitals. Fifteen cases with Barrett's metaplasia and 5 control cases from the same patient population were included in the analysis. HSP expression was quantitatively assessed and classified as high or low. Kaplan-Meier analyses and Cox regression models adjusting for age and sex as well as tumor site, stage, and grade were used to evaluate the effect on survival.
RESULTS
Tumor stage and surgical treatment were the main prognostic factors. High HSP27 expression in cancer cases was a strong negative predictive factor, with a mean survival of 23 mo compared to the 49 mo in cases with a low expression ( = 0.018). The results were similar for HSP70, with a poorer survival of 17 mo in cases with high HSP70 expression, in contrast to 40 mo ( = 0.006) in cases with a low expression. A Cox regression survival analysis was performed, adjusting for possible confounding factors, and higher HSP27 and HSP70 expressions remained an independent negative prognostic factor. The HSPs' correlation with survival was not affected by cancer treatments. When the analysis was adjusted for all factors, the odds ratios for HSP27 and HSP70 were 3.3 (CI: 1.6-6.6, = 0.001) and 2.2 (CI: 1.2-3.9, = 0.02), respectively.
CONCLUSION
HSP27 and HSP70 overexpression is associated with poor survival in EAC, which is, to the best of our knowledge, reported for the first time.
背景
热休克蛋白（HSPs）的过表达与多种恶性肿瘤相关，除了抑制细胞死亡外，还促进癌症的发生、发展和转移。近年来，针对多种恶性肿瘤使用HSP抑制剂的研究十分活跃。由于食管腺癌（EAC）预后较差，寻找新的癌症治疗生物标志物具有重要价值。
目的
评估HSP27和HSP70在EAC中的表达及其对生存的影响。
方法
对1990年至2007年期间在两家大学医院确诊为EAC的93例患者的所有可用样本进行HSP27和HSP70表达的免疫组织化学分析和评估。分析纳入了15例巴雷特化生病例和来自同一患者群体的5例对照病例。对HSP表达进行定量评估并分为高表达或低表达。采用Kaplan-Meier分析和Cox回归模型，对年龄、性别以及肿瘤部位、分期和分级进行调整，以评估其对生存的影响。
结果
肿瘤分期和手术治疗是主要的预后因素。癌症病例中HSP27高表达是一个强烈的阴性预测因素，高表达病例的平均生存期为23个月，而低表达病例为49个月（P = 0.018）。HSP70的结果类似，HSP70高表达病例的生存期较差，为17个月，而低表达病例为40个月（P = 0.006）。进行了Cox回归生存分析，对可能的混杂因素进行了调整，HSP27和HSP70的高表达仍然是独立的阴性预后因素。HSPs与生存的相关性不受癌症治疗的影响。当对所有因素进行调整后，HSP27和HSP70的比值比分别为3.3（CI：(1.6 - 6.6)，P = 0.001）和2.2（CI：(1.2 - 3.9)，P = 0.02）。
结论
据我们所知，HSP27和HSP70过表达与EAC患者的不良生存相关，这是首次报道。
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