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Cluster analyses of the TCGA and a TMA dataset using the coexpression of HSP27 and CRYAB improves alignment with clinical-pathological parameters of breast cancer and suggests different epichaperome influences for each sHSP

Quinlan, Philip R.; Figeuredo, Grazziela; Mongan, Nigel; Jordan, Lee B.; Bray, Susan E.; Sreseli, Roman; Ashfield, Alison; Mitsch, Jurgen; van den Ijssel, Paul; Thompson, Alastair M.; Quinlan, Roy A.

Cluster analyses of the TCGA and a TMA dataset using the coexpression of HSP27 and CRYAB improves alignment with clinical-pathological parameters of breast cancer and suggests different epichaperome influences for each sHSP Thumbnail


Authors

Philip R. Quinlan

NIGEL MONGAN nigel.mongan@nottingham.ac.uk
Professor of Oncology

Lee B. Jordan

Susan E. Bray

Roman Sreseli

Alison Ashfield

Jurgen Mitsch

Paul van den Ijssel

Alastair M. Thompson

Roy A. Quinlan



Abstract

Our cluster analysis of the Cancer Genome Atlas for co-expression of HSP27 and CRYAB in breast cancer patients identified three patient groups based on their expression level combination (high HSP27 + low CRYAB; low HSP27 + high CRYAB; similar HSP27 + CRYAB). Our analyses also suggest that there is a statistically significant inverse relationship between HSP27 and CRYAB and known clinicopathological markers in breast cancer. Screening an unbiased 248 breast cancer patient tissue microarray (TMA) for the protein expression of HSP27 and phosphorylated HSP27 (HSP27-82pS) with CRYAB also identified three patient groups based on HSP27 and CRYAB expression levels. TMA24 also had recorded clinical-pathological parameters, such as ER and PR receptor status, patient survival, and TP53 mutation status. High HSP27 protein levels were significant with ER and PR expression. HSP27-82pS associated with the best patient survival (Log Rank test). High CRYAB expression in combination with wild-type TP53 was significant for patient survival, but a different patient outcome was observed when mutant TP53 was combined with high CRYAB expression. Our data suggest that HSP27 and CRYAB have different epichaperome influences in breast cancer, but more importantly evidence the value of a cluster analysis that considers their coexpression. Our approach can deliver convergence for archival datasets as well as those from recent treatment and patient cohorts and can align HSP27 and CRYAB expression to important clinical-pathological features of breast cancer.

Journal Article Type Article
Acceptance Date Jan 30, 2022
Online Publication Date Mar 2, 2022
Publication Date Mar 2, 2022
Deposit Date Mar 3, 2022
Publicly Available Date Mar 4, 2022
Journal Cell Stress and Chaperones
Print ISSN 1355-8145
Electronic ISSN 1466-1268
Publisher Springer Science and Business Media LLC
Peer Reviewed Peer Reviewed
Volume 27
Issue 2
Pages 177-188
DOI https://doi.org/10.1007/s12192-022-01258-0
Keywords Cell Biology; Biochemistry
Public URL https://nottingham-repository.worktribe.com/output/7534743
Publisher URL https://link.springer.com/article/10.1007/s12192-022-01258-0

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