Systematic Analysis of Spleen Tyrosine Kinase Expression and its Clinical Outcomes in Various Cancers

Background: Spleen tyrosine kinase (SYK) is an important enzyme in the proliferation and differentiation of all hematopoietic tissues. Its role as a cancer driver is well documented in liquid tumors; however, cumulative evidence has suggested an opposite role in other tumor types.

Objectives: To systematically assess the expression of SYK, its prognostic value and epigenetic status in different cancers using bioinformatics tools.

Methods: In this bioinformatics study, Oncomine database and cBioPortal were used to study the SYK gene expression, Kaplan-Meier plotter to study its prognostic value and MethHC to assess the SYK gene methylation in various cancers.

Results: From 542 unique analyses of the SYK gene, it was found to be overexpressed in bladder, breast and colon cancers but downregulated in leukemia, lymphoma and myeloma. Compared with normal tissues, breast and brain tumors showed an overexpression of the SYK gene, whereas lymphoma and leukemia had lower expression. The Kaplan-Meier survival analysis revealed that SYK expression in pancreatic, gastric, liver and lung patients were correlated with better overall survival. Using cBioPortal, prostate cancer was found to have the highest SYK gene mutation frequency, and the mean expression was highest in diffuse large B-cell lymphoma, acute myeloid leukemia and thymoma. Using the MethHC database, SYK promoter hypermethylation was found to be significantly higher in breast, renal, liver, lung, pancreatic, prostatic, skin and stomach cancers compared with the normal tissue (P < 0.005).

Conclusion: The results of this study indicate the potential use of SYK as a diagnostic and therapeutic target for different type of cancers. However, further experimental data are required to validate these results before use of SYK in clinical settings.

Keywords: Cancer; expression; methylation; mutation; spleen tyrosine kinase; survival rate.