Prognostic value of protein tyrosine kinase 6 overexpression in cancers: a meta-analysis.

Hyeong Su Kim,Jae-Jun Lee,Jung Han Kim,Soo Young Jeong,Sung Taek Park

doi:10.31083/j.fbl2702060

Abstract

Protein tyrosine kinase 6 (PTK6) plays an important role in cell proliferation and differentiation. However, the functions of PTK6 appear highly context-dependent and differ depending on the cell type, as well as its intracellular localization. High PTK6 expression in tumor has been associated with poor pathological features and prognosis in some studies, but other studies have reported opposite results. Therefore, we performed this meta-analysis to derive more precise estimations of the association of PTK6 expression with prognosis and clinicopathological features in cancer patients. We conducted a literature search in PubMed, Ovid MEDLINE, and MEDLINE databases to cover all articles published until June 2021. All 1475 patients from the eight studies were included in the meta-analysis. Because of heterogeneity in PTK6 expression in non-tumor tissues, the included studies were divided into two subgroups according to PTK expression in non-tumor tissues: the low expression subgroup (LESG) or high expression subgroup (HESG). Patients with high PTK expression showed significantly worse overall survival (OS) in LESG (Hazard Ratio (HR) = 2.53 [95% Confidence Interval (CI), 1.68-3.83], p < 0.0001), but significantly better OS in HESG (HR = 0.56 [95% CI, 0.40-0.78], p = 0.0006). PTK6 expression also showed different associations with clinicopathological features, such as advanced T classification, stage, and differentiation according to PTK6 expression in non-tumor tissues. PTK6 expression in tumor was a prognostic factor in patients with various cancers, but the direction of prognosis differs, depending on the degree of PTK6 expression in non-tumor tissues.

Highlights

Protein tyrosine kinase 6 (PTK6), a member of a distinct family of non-receptor tyrosine kinases closely related to Src kinases, plays an important role in cell proliferation and differentiation by transferring signals from cell surface receptors to intracellular targets [1,2].The PTK6 protein consists of a tyrosine kinase domain, along with SH2(Src-homology) and SH3 domains, of which SH3 seems more important for the regulation of catalytic activity [3]
We conducted a literature search in PubMed, Ovid MEDLINE, and MEDLINE databases to cover all articles published until June 2021, with the following search terms in their titles, abstracts or keyword lists: ‘PTK6 or Protein tyrosine kinase 6 or Brk or Breast tumor kinase’ and ‘cancer or carcinoma or malignancy or tumor or neoplasm’
Studies that discussed the following points were included in this meta-analysis: (i) evaluation of PTK6 expression by immunohistochemical (IHC) staining; (ii) relationships between PTK6 expression level and clinicopathological features of the patients or sufficient published data to estimate the hazard ratio (HR) for survival; and (iii) articles written in English

Summary

Introduction

Protein tyrosine kinase 6 (PTK6), a member of a distinct family of non-receptor tyrosine kinases closely related to Src kinases, plays an important role in cell proliferation and differentiation by transferring signals from cell surface receptors to intracellular targets [1,2].The PTK6 protein consists of a tyrosine kinase domain, along with SH2(Src-homology) and SH3 domains, of which SH3 seems more important for the regulation of catalytic activity [3]. Protein tyrosine kinase 6 (PTK6) plays an important role in cell proliferation and differentiation. High PTK6 expression in tumor has been associated with poor pathological features and prognosis in some studies, but other studies have reported opposite results. We performed this meta-analysis to derive more precise estimations of the association of PTK6 expression with prognosis and clinicopathological features in cancer patients. Results: Patients with high PTK expression showed significantly worse overall survival (OS) in LESG (Hazard Ratio (HR) = 2.53 [95% Confidence Interval (CI), 1.68–3.83], p < 0.0001), but significantly better OS in HESG (HR = 0.56 [95% CI, 0.40–0.78], p = 0.0006). PTK6 expression showed different associations with clinicopathological features, such as advanced T classification, stage, and differentiation according to PTK6 expression in non-tumor tissues. Conclusions: PTK6 expression in tumor was a prognostic factor in patients with various cancers, but the direction of prognosis differs, depending on the degree of PTK6 expression in non-tumor tissues

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Discussion

Conclusion