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Expression of Syk and MAP4 proteins in ovarian cancer

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

Expression of Syk and MAP4 proteins in ovarian cancer Thumbnail


Siwei Zhang

Suha Deen

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Assistant Professor

Anqi Yao

Professor of Cancer and Radiation Biology


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.

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.

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).

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.

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
Keywords MAP4; Syk; Calpain; Calpastatin; Ovarian cancer; Chemotherapy
Public URL
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Additional Information The authors declare no conflict of interest.; Permission to use the archived tissue was obtained from Derbyshire Ethics Committee (07/H0401/156).