Abstract
Ovarian cancer, one of the most common gynecological malignancies, has an aggressive phenotype. It is necessary to develop novel and more effective treatment strategies against advanced disease. Protein tyrosine kinases (PTKs) play an important role in the signal transduction pathways involved in tumorigenesis, and represent potential targets for anticancer therapies. In this study, we performed cDNA subtraction following polymerase chain reaction (PCR) using degenerate oligonucleotide primers to identify specifically overexpressed PTKs in ovarian cancer. Three PTKs, janus kinase 1, insulin-like growth factor 1 receptor, and discoidin domain receptor 1 (DDR1), were identified and only DDR1 was overexpressed in all ovarian cancer tissues examined for the validation by quantitative real-time PCR. The DDR1 protein was expressed in 63% (42/67) of serous ovarian cancer tissue, whereas it was undetectable in normal ovarian surface epithelium. DDR1 was expressed significantly more frequently in high-grade (79%) and advanced stage (77%) tumors compared to low-grade (50%) and early stage (43%) tumors. The expression of the DDR1 protein significantly correlated with poor disease-free survival. Although its functional role and clinical utility remain to be examined in future studies, our results suggest that the expression of DDR1 may serve as both a potential biomarker and a molecular target for advanced ovarian cancer.
Highlights
Ovarian cancer, one of the most common gynecological malignancies, is an aggressive cancer associated with high morbidity and mortality, especially in the case of advanced disease.ovarian cancer is rarely diagnosed in its early, most curable stages, and the tumors are already disseminated abdominally in 75% of patients at the time of diagnosis
140 clones were revealed to be identical to janus kinase 1 (JAK1), 30 to the insulin-like growth factor 1 receptor (IGF1-R), and eight to the discoidin domain receptor 1 (DDR1)
The DDR1 gene was overexpressed in all eight individuals, whereas the expression levels of JAK1 and IGF1-R were not increased in half of the ovarian cancer tissue samples (Figure 1)
Summary
One of the most common gynecological malignancies, is an aggressive cancer associated with high morbidity and mortality, especially in the case of advanced disease.ovarian cancer is rarely diagnosed in its early, most curable stages, and the tumors are already disseminated abdominally in 75% of patients at the time of diagnosis. The tumor grade, histological type, and presence of residual disease after initial surgery are important clinicopathological factors related to patient outcome [1]. Protein tyrosine kinases (PTKs) play an important role in the signal transduction pathways that control cell proliferation and differentiation, and are involved in tumorigenesis. The PTKs may provide an important predictive marker for therapeutic response and patient outcome [6,7]. It is important to identify predictive PTKs to identify targeted subpopulations of patients who will respond to both the existing tyrosine kinase inhibitors (TKIs) and to new agents developed against new targets, and to obtain a better understanding of the underlying mechanisms of resistance to the existing agents so that new compounds can be developed to overcome this resistance
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