Prognostic value of spleen tyrosine kinase in human solid tumors

OncoTargets and Therapy, Jun 2018

Prognostic value of spleen tyrosine kinase in human solid tumors Beibei Ni,1,2 Shi Li,1,2 Yang Liu,1,2 Yuqian Huang,1,2 Zesong Li1,2 1Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Shenzhen Key Laboratory of Genitourinary Tumor, First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, People’s Republic of China Background: Spleen tyrosine kinase (SYK) was reported to be dysregulated in solid tumors and played an important role in cancer progression. However, the clinical and prognostic values of SYK in solid tumors remain unclear. This meta-analysis investigated the association between SYK expression and clinical outcomes in the patients with solid tumors. Methods: A comprehensive literature search was conducted by screening the online electronic databases of PubMed, Embase, and the China National Knowledge Infrastructure. The hazard ratio (HR) with its corresponding 95% CI was used to explore the prognostic value of SYK. Results: We analyzed a total of 1,075 patients from 10 studies, which met the criteria for this meta-analysis. Our pooled results demonstrated that a low expression of SYK did not correlate significantly with shorter overall survival (OS; HR=0.64, 95% CI: 0.34–1.21, P=0.169) or poorer disease-free survival (HR=0.51, 95% CI: 0.13–2.02, P=0.338). However, in a subgroup analysis based on tumor type and test method, under-expression of SYK was positively associated with worse OS in the groups of breast cancer (BC; HR=0.51, 95% CI: 0.32–0.80, P=0.003), hepatocellular carcinoma (HCC; HR=0.44, 95% CI: 0.29–0.69, P<0.001), methylation (HR=0.39, 95% CI: 0.30–0.51, P<0.001), and quantitative reverse transcription polymerase chain reaction (HR=0.24, 95% CI: 0.09–0.65, P=0.005). Conclusion: This meta-analysis demonstrated that under-expression of SYK may serve as a predictive biomarker for poor prognosis in BC and HCC patients. In other solid tumors, the clinical usefulness should be confirmed by large-scale studies. Keywords: spleen tyrosine kinase, solid tumor, prognosis, meta-analysis

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Prognostic value of spleen tyrosine kinase in human solid tumors

OncoTargets and Therapy Prognostic value of spleen tyrosine kinase in human solid tumors 0 s henzhen Key laboratory of genitourinary Tumor, First a ffiliated h ospital of s henzhen University , s henzhen s econd People's hospital, shenzhen, guangdong, People's republic of china 1 g uangdong Key l aboratory of systems Biology and synthetic Biology for Urogenital Tumors, First affiliated hospital of shenzhen University, shenzhen second People's hospital , s henzhen, g uangdong, People's republic of china 2 Yuqian huang PowerdbyTCPDF(ww.tcpdf.org) Background: Spleen tyrosine kinase (SYK) was reported to be dysregulated in solid tumors and played an important role in cancer progression. However, the clinical and prognostic values of SYK in solid tumors remain unclear. This meta-analysis investigated the association between SYK expression and clinical outcomes in the patients with solid tumors. Methods: A comprehensive literature search was conducted by screening the online electronic databases of PubMed, Embase, and the China National Knowledge Infrastructure. The hazard ratio (HR) with its corresponding 95% CI was used to explore the prognostic value Results: We analyzed a total of 1,075 patients from 10 studies, which met the criteria for this meta-analysis. Our pooled results demonstrated that a low expression of SYK did not correlate significantly with shorter overall survival (OS; HR=0.64, 95% CI: 0.34-1.21, P=0.169) or poorer disease-free survival (HR=0.51, 95% CI: 0.13-2.02, P=0.338). However, in a subgroup analysis based on tumor type and test method, under-expression of SYK was positively associated with worse OS in the groups of breast cancer (BC; HR=0.51, 95% CI: 0.32-0.80, P=0.003), hepatocellular carcinoma (HCC; HR=0.44, 95% CI: 0.29-0.69, P,0.001), methylation (HR=0.39, 95% CI: 0.30-0.51, P,0.001), and quantitative reverse transcription polymerase chain reaction Conclusion: This meta-analysis demonstrated that under-expression of SYK may serve as a predictive biomarker for poor prognosis in BC and HCC patients. In other solid tumors, the clinical usefulness should be confirmed by large-scale studies. spleen tyrosine kinase; solid tumor; prognosis; meta-analysis - open access to scientific and medical research O r i g i n a l r e s e a r c h Introduction Cancer is one of the leading causes of morbidity and mortality worldwide.1 With the recent advances in precision medicine, the subclassification of cancer according to genotype, mutations, or biomarkers became the guidance in the selection of cancer treatments and the factor in prognosis.2 It is of great importance to investigate the potential biomarkers in cancers for both diagnostic and prognostic purposes. The spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase that is expressed in most hematopoietic cells and functions as a hematopoietic cell-specific signaling molecule.3,4 SYK was first found to be a potential tumor suppressor in breast carcinoma in 2000.5 Since then, a growing amount of researches on SYK has been performed in non-hematopoietic tumors.6–8 Several clinical observations have indicated that patients with a low SYK expression have a significantly poorer prognosis than those with a high SYK expression.9–12 Functional studies have shown that overexpression of SYK is associated with cancer proliferation and metastasis.13–15 Epigenetic silencing through hypermethylation of promoter CpG islands has been proposed to be involved in the loss of SYK expression in various cancers.16–19 Yang et al12 have reported that the expression level of SYK in tumor samples with unmethylated SYK gene was significantly higher than that in samples with methylated SYK gene. What is more, SYK methylation is correlated with poor overall survival (OS) in colorectal cancer (CRC). These data implicate SYK as a putative tumor suppressor in cancer. Contradictorily, recent studies have shown that SYK is upregulated in multiple types of tumors, including nasopharyngeal carcinoma (NPC),20 small-cell lung cancer,21 and squamous cell carcinoma of the head and neck cancer (SCCHN),22 suggesting that SYK may serve as a proto-oncogene. Taken together, we suspect that SYK played complicated roles in multiple cancer types. Nevertheless, the prognostic value of SYK in cancer has not yet been fully elucidated. No meta-analysis has been conducted to assess the association between SYK and 8 1 0 2 l u J 2 1 n o 1 2 1 . 9 5 . 2 3 . 3 1 2 y b / m o c . rvpee l.yno tpheerfsourrmveivdaal mofeptaa-taiennatlsyswisittho caasnsecsesrsthseopfraorg.nTohsetircefvoarleu,ewoef s s .dow lsue SYK in patients with various solid tumors. OS and disease/ww ano free survival (DFS) were the primary end points. / :s rs ttp pe h ro from F d e d a o l n w o d y p a r e h T d n a s t e g r a T o c n O Methods search strategies The present study performed a thorough search for available literatures in databases of PubMed, Embase, and the China National Knowledge Infrastructure (CNKI (...truncated)


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Beibei Ni, Shi Li, Yang Liu, Yuqian Huang, Zesong Li. Prognostic value of spleen tyrosine kinase in human solid tumors, OncoTargets and Therapy, 2018, pp. 3377-3384, DOI: 10.2147/OTT.S163136