PTK7 overexpression in colorectal tumors: Clinicopathological correlation and prognosis relevance

Abstract

Colorectal cancer (CRC) has one of the highest mortality rates in the worldwide and its incidence has been increasing in recent years. Protein tyrosine kinase-7 (PTK7) is an inactive member of receptor protein tyrosine kinase (RPTK)-like molecules, which is involved in tumorigenesis of a variety of cancers. Our study aimed to investigate expression of PTK7 in colorectal tumors (including benign adenomas and malignant carcinomas), and its potential function in tumorigenesis and prognosis. A total of 209 CRC patients and 28 colonic adenoma patients were included in this study. Reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time PCR were performed in 14 pairs of fresh frozen tissues to evaluate mRNA expression of PTK7. Expression of PTK7 protein in 209 CRC tissues with paired non-cancerous mucosa and 28 adenoma specimens were tested using immunohistochemistry. The expression difference and its correlation with clinicopathological features and overall survival were assessed by SPSS statistics (version 22). P<0.05 was considered significant. RT-PCR and quantitative real-time PCR showed a higher expression of PTK7 mRNA in CRC compared with non-tumorous mucosa (4.87±3.71 vs. 1.33±1.05; P<0.001). PTK7 expression was significantly higher in adenoma (75%) and CRC (68.3%) than in non-tumorous mucosa (P<0.001). PTK7 expression was correlated with tumor differentiation (P=0.027), lymph node metastasis (P=0.005), distant metastasis (P=0.001) and TNM stage (P=0.028) of CRC patients. Significant correlation between PTK7 overexpression and favorable overall survival of CRC patients was observed (P=0.005). Therefore, it may act as a candidate biomarker to predict the occurrence and prognosis of colorectal tumor.

Figure 1

Protein tyrosine kinase-7 (PTK7) mRNA expression in colorectal cancer (CRC) tissues and matched non-cancerous mucosa. (A) In 12/14 pairs of tissues, PTK7 mRNA expression was higher in CRC tissues than in matched non-cancerous mucosa. (B) According to 2^−ΔΔCt value, independent t-test was performed. The results further proved PTK7 mRNA expressed in high level in CRC tissues (4.87±3.71), while in low level in matched non-cancerous mucosa (1.33±1.05). 'T' indicates 'colorectal tumour tissues', 'N' indicates 'normal mucosa'; ^***indicates a significant difference (P<0.001).

Figure 2

Typical immunohistochemical staining of protein tyrosine kinase-7 (PTK7) in (A) benign adenoma (B) colorectal cancer tissue and (C) non-cancerous mucosa (magnification: left, ×100; right, ×200). A typical cytoplasmic staining of PTK7 is shown in the pictures.

Figure 3

Positive expression rate of protein tyrosine kinase-7 (PTK7) in tumor samples with diverse clinicopathological features. (A) PTK7 was expressed significantly higher (P=0.027) in well-differentiated tumors (90%), while the expression rate was reduced in moderately differentiated tumors (68.5%) and poorly differentiated tumors (54.5%). (B) Early-stage tumors (77.9%) had markedly higher (P=0.028) expression rate of PTK7 than advanced stage tumor (62.6%). (C) PTK7 expressed distinctly higher (P=0.005) in patients without lymph node metastasis (79.1%) than in patients with lymph node metastasis (60.3%). (D) Patients without distant metastasis (78.8%) had significantly higher (P=0.001) expression of PTK7 than those with distant metastasis (57%). (E) PTK7 expression rate ascended from small-sized tumors, medium-sized tumors to large-sized tumors (65.7, 70.40 and 72.7%, respectively), though the difference was not significant. (F) Tumors that invaded within muscularis proria (83.3%) had higher PTK7 expression than those penetrated through muscularis proria (65.7%). (G) Patients with vascular invasion (70.4%) had higher PTK7 expression than those without vascular invasion (63.3%).

Figure 4

Protein tyrosine kinase-7 (PTK7) expression in non-tumorous mucosa (48/228), adenoma (21/28) and CRC tissues (138/202).^**P<0.01; NS, not significant.

Figure 5

Kaplan-Meier survival analysis according to protein tyrosine kinase-7 (PTK7) expression in all patients showed that patients with positive expression of PTK7 had a better overall survival (87.11±3.67 months) than those with negative expression of PTK7 (40.11±3.48 months) (P=0.005).