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High expression of GRP78/BiP as a novel predictor of favorable outcomes in patients with advanced thymic carcinoma

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Abstract

Background

Glucose-regulated protein (GRP) 78/immunoglobulin heavy chain binding protein (BiP) is a member of the endoplasmic reticulum chaperone family, and its role in various types of human malignancies has recently been investigated. However, the clinicopathological characteristics of GRP78/BiP in advanced thymic carcinoma (ATC) remain unknown. We aimed to examine the relationship between GRP78/BiP expression and the clinical outcomes of ATC patients.

Methods

Thirty-four patients with ATC receiving combination chemotherapy at three institutions between April 1998 and April 2014 were enrolled in this study. We retrospectively collected patient characteristics such as therapeutic efficacy, pathological findings, and survival data from their medical records. We performed immunohistochemical analysis to evaluate the expression of GRP78/BiP in tumor specimens obtained from surgical resection or biopsy.

Results

This study included 21 men (68%) and 13 women (32%) with a median age of 62 years (range 36–75 years). GRP78/BiP overexpression was observed in 65% of the patients (22 of 34 patients). There was no correlation between GRP78/BiP expression and any patient characteristic. Patients with a high level of GRP78/BiP expression had significantly longer overall survival (OS) compared to those with a low level (46.2 vs. 16.8 months, p = 0.04). Multivariate analysis demonstrated that a high level of GRP78/BiP expression was an independent prognostic factor for prolonged OS.

Conclusions

Our findings indicate that the overexpression of GRP78/BiP is a novel predictor of favorable outcomes in patients with ATC who receive combination chemotherapy.

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Acknowledgements

The authors would like to thank Dr. Akira Mogi, Department of General Surgical Science, Dr. Kimihiro Shimizu, Department of Thoracic Visceral Organ Surgery, and Dr. Masataka Maeno, Department of Medicine and Biological Science, for data collection. We would like to show our appreciation for technical assistance with immunohistochemical analysis to the staff in the pathology departments of the Gunma University Hospital, Gunma Prefectural Cancer Center, and National Hospital Organization Shibukawa Medical Center. This work was supported in part by grant 26461154 (KK) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

Author information

Correspondence to Kyoichi Kaira.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were carried out in accordance with the ethical standards of the institutional and/or national research committee and in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

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Miura, Y., Kaira, K., Sakurai, R. et al. High expression of GRP78/BiP as a novel predictor of favorable outcomes in patients with advanced thymic carcinoma. Int J Clin Oncol 22, 872–879 (2017). https://doi.org/10.1007/s10147-017-1142-x

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Keywords

  • Thymic carcinoma
  • Glucose-regulated protein 78/immunoglobulin heavy chain binding protein
  • Endoplasmic reticulum stress
  • Prognostic factor
  • Biomarker