Retrospective Cohort Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Feb 6, 2019; 7(3): 260-269
Published online Feb 6, 2019. doi: 10.12998/wjcc.v7.i3.260
Overexpression of HSP27 and HSP70 is associated with decreased survival among patients with esophageal adenocarcinoma
Henna K Söderström, Juha T Kauppi, Niku Oksala, Timo Paavonen, Leena Krogerus, Jari Räsänen, Tuomo Rantanen
Henna K Söderström, Juha T Kauppi, Jari Räsänen, Department of General Thoracic Surgery, Helsinki University Central Hospital, Helsinki 00029, Finland
Niku Oksala, Faculty of Medicine and Life Sciences, University of Tampere, Tampere 33014, Finland
Niku Oksala, Department of Vascular Surgery, Tampere University Hospital, Tampere 33520, Finland
Timo Paavonen, Department of Pathology, Fimlab Laboratories and Department of Medicine and Life Sciences, University of Tampere, Tampere 33520, Finland
Leena Krogerus, Department of Pathology, Helsinki University Central Hospital, 00029 Helsinki 00029, Finland
Tuomo Rantanen, Department of Surgery, Kuopio University Hospital, Kuopio 70029, Finland
Tuomo Rantanen, Department of Surgery, Institute of Clinical Medicine, University of Eastern Finland, Kuopio 70029, Finland
Author contributions: All the authors contributed to this paper.
Institutional review board statement: The study has been approved by the Ethics Committee at Helsinki University Central Hospital.
Informed consent statement: Because of retrospective study signed informed consent form is not needed. However, Helsinki University Hospital has given permission to conduct this study.
Conflict-of-interest statement: Authors have no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Tuomo Rantanen, MD, PhD, Professor, Department of Surgery, Kuopio University Hospital, Box 100, Kuopio 70029, Finland. tuomo.rantanen@kuh.fi
Telephone: +358-50-4028461 Fax: +358-17-173 599
Received: November 19, 2018
Peer-review started: November 19, 2018
First decision: December 5, 2018
Revised: December 21, 2018
Accepted: December 29, 2018
Article in press: December 30, 2018
Published online: February 6, 2019
Abstract
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 (P = 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 (P = 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, P = 0.001) and 2.2 (CI: 1.2–3.9, P = 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.

Keywords: Esophageal adenocarcinoma, Heat shock proteins, Heat shock protein 27, Heat shock protein 70, Overexpression, Survival

Core tip: Heat shock proteins (HSPs) are classified according to molecular weight into distinct protein families, and they are present in all human cells. Overexpression of 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. Because of the poor prognosis of esophageal adenocarcinoma (EAC), it would be valuable to find new biomarkers for the development of cancer treatments. We conducted the present study to analyze the expression of HSP27 and HSP70, and their association with survival, in patients with EAC.