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. 2019 Apr;145(4):909-919.
doi: 10.1007/s00432-019-02856-9. Epub 2019 Feb 8.

Expression of Syk and MAP4 proteins in ovarian cancer

Siwei Zhang  1 , Suha Deen  2 , Sarah J Storr  1 , Anqi Yao  1 , Stewart G Martin  3
Affiliations

Expression of Syk and MAP4 proteins in ovarian cancer

Siwei Zhang et al. J Cancer Res Clin Oncol. 2019 Apr.

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 < 0.001), stage (P = 0.001), grade (P < 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 < 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.

Keywords: Calpain; Calpastatin; Chemotherapy; MAP4; Ovarian cancer; Syk.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Representative photomicrographs of Syk and MAP4 expression in ovarian carcinoma cells. Expression levels, including low (left), medium (middle) and high (right) staining, of Syk and MAP4 at × 10 magnification with × 20 magnification inset panel. Negative controls omitted primary antibody. Scale bar represents 100 µm
Fig. 2
Fig. 2
Kaplan–Meier survival curves show the impact of Syk-c, Syk-n and MAP4 expression on overall survival and progression-free survival. There were no differences in survival between patients with tumours expressing high MAP4 or Syk and those with tumours expressing low MAP4 or Syk. Significance was determined using the log-rank test. The tables shown below the Kaplan–Meier survival curves listed the number of patients at risk at the specific months. High expression—black line, low expression—grey line
Fig. 3
Fig. 3
Kaplan–Meier survival curves show the impact of Syk expression on overall survival in different subgroups. Survival analysis shows that high Syk-n expression significantly associated with better (P = 0.010) overall survival for ovarian cancer patients resistant to platinum-based chemotherapy (a), patients with tumour confined to the ovaries (b) and patients with no residual carcinoma (c). Significance was determined using the log-rank test. The tables shown below the Kaplan–Meier survival curves listed the number of patients at risk at the specific months. High expression—black line, low expression—grey line
See this image and copyright information in PMC

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