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未磷酸化和磷酸化热休克蛋白 27 作为胰腺导管腺癌预后生物标志物的意义。

Significance of unphosphorylated and phosphorylated heat shock protein 27 as a prognostic biomarker in pancreatic ductal adenocarcinoma.

机构信息

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asklepios Hospital Barmbek, Hamburg, Germany.

Asklepios Campus Hamburg, Semmelweis University Budapest, Hamburg, Germany.

出版信息

J Cancer Res Clin Oncol. 2020 May;146(5):1125-1137. doi: 10.1007/s00432-020-03175-0. Epub 2020 Mar 21.

Abstract

PURPOSE

Few studies reported about the potential of unphosphorylated heat shock protein 27 (HSP27) and phosphorylated heat shock protein 27 (pHSP27) as a predictor for survival and gemcitabine resistance in pancreatic ductal adenocarcinoma (PDAC). In this study, we analysed the expression patterns of pHSP27 and HSP27 in a patient population after surgery and correlated the immunohistochemical results with clinicopathological data and long-term outcome of the patients.

METHODS

HSP27 and pHSP27 (Ser-15, Ser-78 and Ser-82) protein expression were analysed by immunohistochemistry using the immunoreactive score (IRS) from paraffin-embedded tissue of 106 patients with PDAC who underwent surgery. Immunohistochemical results were correlated with clinicopathological data, disease-free (DFS) and overall survival (OS).

RESULTS

HSP27 expression was significantly lower in patients with a shorter OS (p = 0.006) and DFS (p < 0.0001). A higher HSP27 expression was associated with a better response to gemcitabine in the resected, non-metastasised patients group (p = 0.001). Furthermore, HSP27 was downregulated in patients suffering from metastases at time of surgery (p < 0.001) and in undifferentiated tumours (p = 0.007). In contrast, pHSP27-Ser15, -Ser78 and -Ser82 were not associated with any survival data of the study population.

CONCLUSION

HSP27 seems to be a strong indicator for the prediction of OS and DFS. Moreover, HSP27 could play a role in the formation and migration of liver metastases of PDAC.

摘要

目的

很少有研究报道未磷酸化热休克蛋白 27(HSP27)和磷酸化热休克蛋白 27(pHSP27)作为胰腺导管腺癌(PDAC)患者生存和吉西他滨耐药的预测因子的潜力。在这项研究中,我们分析了手术后患者人群中 pHSP27 和 HSP27 的表达模式,并将免疫组织化学结果与临床病理数据和患者的长期结果相关联。

方法

使用免疫反应评分(IRS)分析了 106 例接受手术的 PDAC 患者石蜡包埋组织中的 HSP27 和 pHSP27(Ser-15、Ser-78 和 Ser-82)蛋白表达。免疫组织化学结果与临床病理数据、无病生存期(DFS)和总生存期(OS)相关联。

结果

HSP27 表达与较短的 OS(p=0.006)和 DFS(p<0.0001)相关。在接受吉西他滨治疗的切除、无转移患者组中,较高的 HSP27 表达与更好的反应相关(p=0.001)。此外,在手术时患有转移的患者(p<0.001)和未分化肿瘤的患者(p=0.007)中 HSP27 下调。相比之下,pHSP27-Ser15、-Ser78 和 -Ser82 与研究人群的任何生存数据均无关联。

结论

HSP27 似乎是预测 OS 和 DFS 的有力指标。此外,HSP27 可能在 PDAC 肝转移的形成和迁移中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8480/11804573/13fc35c5b7de/432_2020_3175_Fig1_HTML.jpg

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