Expression of Syk and MAP4 proteins in ovarian cancer

Zhang, Siwei; Deen, Suha; Storr, Sarah J.; Yao, Anqi; Martin, Stewart G.

Abstract

Purpose
We have previously reported on the prognostic importance of the calpain family of proteins in ovarian cancer, especially calpain-2. Spleen tyrosine kinase (Syk) phosphorylates a variety of cytoskeletal proteins with studies suggesting potential interactions between Syk and conventional calpains. Microtubule-associated protein 4 (MAP4) has been reported to be regulated by Syk.

Methods
The current study assessed Syk and MAP4 protein expression, by immunohistochemistry on a tissue microarray comprised of cores from primary ovarian carcinomas (n = 575), to evaluate associations with patient clinical outcomes and other clinicopathological factors and sought to determine whether there were any correlations between the expression of Syk, MAP4 and the calpain system.

Results
MAP4 expression was significantly associated with ovarian cancer histological subtype (P [less than] 0.001), stage (P = 0.001), grade (P [less than] 0.001) and residual tumour (P = 0.005). Despite this finding, we found no significant association existing between MAP4 expression and overall survival. Syk expression was also found significantly associated with histological subtype (P [less than] 0.001). Syk seems to play a contradictory role with respect to tumour progression: low cytoplasmic Syk expression was significantly associated with low stage (P = 0.013), and low nuclear Syk expression with chemo-resistance in patients treated with taxane-containing therapy (P = 0.006). Interestingly, despite the lack of association in the whole cohort, high nuclear Syk expression was significantly associated with better overall survival in certain subgroups (P = 0.001).

Conclusions
The current study indicates a lack of correlation between calpain-2 expression and Syk and MAP4. Syk, MAP4 and calpain-1 appeared to significantly correlate with each other in the whole cohort, with calpain-1 being more highly associated with MAP4 and Syk in mucinous carcinomas. Overall, the current results suggest that Syk, MAP4, and calpain-1 expression are correlated with each other and these proteins may be involved in early stages of tumour spread.

Citation

Zhang, S., Deen, S., Storr, S. J., Yao, A., & Martin, S. G. (2019). Expression of Syk and MAP4 proteins in ovarian cancer. Journal of Cancer Research and Clinical Oncology, 145(4), 909–919. https://doi.org/10.1007/s00432-019-02856-9

• Journal Article Type: Article
• Acceptance Date: Feb 1, 2019
• Online Publication Date: Feb 8, 2019
• Publication Date: 2019-04
• Deposit Date: Feb 14, 2019
• Publicly Available Date: Feb 14, 2019
• Journal: Journal of Cancer Research and Clinical Oncology
• Print ISSN: 0171-5216
• Electronic ISSN: 1432-1335
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 145
• Issue: 4
• Pages: 909–919
• DOI: https://doi.org/10.1007/s00432-019-02856-9
• Keywords: MAP4; Syk; Calpain; Calpastatin; Ovarian cancer; Chemotherapy
• Public URL: https://nottingham-repository.worktribe.com/output/1547339
• Publisher URL: https://link.springer.com/article/10.1007%2Fs00432-019-02856-9
• Additional Information: The authors declare no conflict of interest.; Permission to use the archived tissue was obtained from Derbyshire Ethics Committee (07/H0401/156).
• Contract Date: Feb 14, 2019