High expression of HSP90 is associated with poor prognosis in patients with colorectal cancer

Shuming Zhang; Shichao Guo; Zhangfu Li; Dan Li; Qimin Zhan

doi:10.7717/peerj.7946

High expression of HSP90 is associated with poor prognosis in patients with colorectal cancer

PeerJ. 2019 Oct 31:7:e7946. doi: 10.7717/peerj.7946. eCollection 2019.

Authors

Shuming Zhang¹, Shichao Guo¹, Zhangfu Li¹, Dan Li¹, Qimin Zhan^{1

2}

Affiliations

¹ State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Laboratory of Molecular Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, China.

Abstract

Background: Heat shock protein 90 (HSP90) is a highly conserved chaperone with an approximate molecular weight of 90-kDa. It plays a critical role in maintaining stability and homeostasis of oncoproteins, helping cancer cells living in the unsuitable environmental conditions. The current study aims to inquire the difference of HSP90 expression in tumor tissues and normal tissues, analyze the correlation between HSP90 expression and the prognoses of patients with colorectal cancer (CRC), and investigate its role in CRC preliminarily.

Methods: Online analysis of HSP90 mRNA levels in different cancers was firstly done in Gene Expression Profiling Interactive Analysis. Then HSP90 expression was determined by immunohistochemistry between 99 CRC tissues and 81 normal tissues. Chi-square test or Fisher's exact test was used to analyze the relationship between HSP90 and histopathologic characteristics. Kaplan-Meier analysis and Cox's proportional hazards model were also done for further analysis of the prognostic values of HSP90. Pearson's correlation coefficients between HSP90 expression values and other mRNA expression values were calculated based on The Cancer Genome Atlas dataset and bioinformatic analysis was done about these screened genes.

Results: Colorectal cancer tissues showed significantly higher expression of HSP90 than normal tissues (55.6% vs. 3.7%, P < 0.0001). Kaplan-Meier curves showed high HSP90 expression was associated with poor prognosis (P = 0.039) in CRC patients, and multivariate Cox proportional hazards regression model analysis also indicated that HSP90 expression (HR = 1.930, 95% CI [1.113-3.349], P = 0.019) linked to poor prognosis. Moreover, 85 genes were correlated with HSP90, which were involved in metabolic process and enriched in pathways of Proteasome and Base excision repair.

Conclusions: Our results suggested that HSP90 expression is inversely associated with survival outcomes and could be an independent prognostic factor for CRC patients. It mainly involved in metabolic process and exerted binding and catalytic activities.

Keywords: Base excision repair; Colorectal cancer; HSP90; Immunohistochemistry; Outcomes; Overall survival; Prognosis; Proteasome.

Associated data

figshare/10.6084/m9.figshare.9975689.v1

Grants and funding

This work was supported by the National 973 Program (2015CB553904), the National Natural Science Foundation of China (81490753, 81830086 and 81672455), the Beijing Nova Program (xx2018040) and the CAMS Initiative for Innovative Medicine (2017-I2M-3-004). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.