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

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.

Transcriptomics indicate nuclear division and cell adhesion not recapitulated in MCF7 and MCF10A compared to luminal A breast tumours

“…While CRYAB was overexpressed and associated with poorer prognosis in the basal BC subtype and metastasis 107 – 109 , CRYAB was shown to be strongly downregulated in all BC subtypes 110 . Interestingly, separate clusters of BC samples were identified to be varying in CRYAB expression, where CRYAB tended to be less expressed in ER-positive BC but more expressed in ER-negative BC 111 , suggesting a subtype-specific gene expression pattern in CRYAB . While the tumour-suppressive roles of CRYAB in LumA BC are less well-established, CRYAB has been shown to reduce progression in nasopharyngeal cancers by associating with membrane-bound β-catenin, preventing the release of β-catenin into the cytoplasm, thereby suppressing the oncogenic abilities of β-catenin by preventing it from interacting with complexes to facilitate transcription of genes involved in tumour progression 112 .…”