The expression and prognostic value of protein tyrosine kinase 6 in early-stage cervical squamous cell cancer

Abstract

Background: Protein tyrosine kinase 6 (PTK6) is overexpressed in many epithelial tumors and predicts poor prognosis. However, PTK6 expression status and its role in cervical squamous cell cancer are unknown. This study aimed to investigate the expression level and clinical significance of PTK6 in early-stage cervical squamous cell cancer.

Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting analysis were performed to detect PTK6 mRNA and protein expression levels in 10 freshly frozen, early-stage cervical squamous cell cancer specimens and adjacent non-tumorous cervical tissues. The expression of PTK6 was detected using immunohistochemical staining in 150 formalin-fixed, paraffin-embedded, early-stage cervical squamous cell cancer sections and 10 normal cervical tissue sections.

Results: The mRNA and protein levels of PTK6 in cancer tissues were higher than those in adjacent non-tumorous cervical tissues. Immunohistochemical analysis showed that PTK6 was not expressed in normal cervical tissues but was overexpressed in the cytoplasm of cervical squamous cell cancer cells. The level of PTK6 expression was significantly associated with tumor grade (P = 0.020). The 5-year overall survival rate of patients with high PTK6 expression was lower than that of patients with low PTK6 expression (81.3% vs. 96.2%, P = 0.008). Multivariate Cox regression analysis showed that the expression level of PTK6 in cervical squamous cell cancer was an independent prognostic factor for patient survival (hazard ratio = 5.999, 95% confidence interval 1.622-22.191, P < 0.05).

Conclusions: PTK6 is overexpressed in cervical squamous cell cancer. Increased PTK6 expression is associated with reduced 5-year overall survival. PTK6 expression is an independent prognostic predictor for cervical cancer.

Keywords: Cervical squamous cell cancer; Immunohistochemistry; PTK6; Prognosis.

Fig. 1

Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting analysis of protein tyrosine kinase 6 (PTK6) expression in early-stage cervical squamous cell cancer tissues. a qRT-PCR analysis of PTK6 mRNA expression in early-stage cervical squamous cell cancer tissues. The mRNA level of PTK6 in cancer tissues (T) is higher than that in paired adjacent non-tumorous cervical tissues (N), and the range of fold increase (average T/N ratio) was 3.6–11.9. b Western blotting analysis of PTK6 protein expression in early-stage cervical squamous cell cancer tissues. The protein level of PTK6 in 10 cervical squamous cell cancer tissues (T) was higher than that in paired adjacent non-tumorous cervical tissues (N). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as the loading control

Fig. 2

Immunohistochemical analysis of PTK6 expression in normal cervical epithelial tissues and cervical squamous cell cancer tissues. a PTK6 protein is not expressed in normal cervical epithelia. b PTK6 protein is weakly stained in the cytoplasm of cervical squamous cell cancer; c PTK6 protein is moderately stained in the cytoplasm of cervical squamous cell cancer; d PTK6 protein is strongly stained in the cytoplasm of cervical squamous cell cancer

Fig. 3

Kaplan-Meier survival curves for early-stage cervical squamous cell cancer patients with low and high PTK6 expression. a high PTK6 expression levels were associated with a short OS in patients with early-stage cervical squamous cell cancer (P = 0.008); b the 5-year DFS rate was similar between these two groups (P = 0.834)