Browsing by Author "Koskinen, Netta"
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Koskinen, Netta (2022)SerpinE2 is a serine protease inhibitor (serpin) family protein that inhibits several extracellular proteases, such as thrombin, urokinase-type plasminogen activator and trypsin. Proteases and their inhibitors are often involved in cancer. SerpinE2 transcripts are upregulated in several cancers and found to predict poor prognosis of cancer patients. However, such studies regarding protein levels of serpinE2 are scarce. In this study, serpinE2 protein was analysed in three urological cancers, with patient groups that address the greatest needs for clinical biomarkers. The major aim of this study was to examine the association of serpinE2 staining with patient survival and clinicopathological features in prostate, urinary bladder and kidney cancers, and to evaluate its usability as an immunohistochemical biomarker. Tissue microarray slides from cancer patient tissues were stained immunohistochemically for serpinE2. The staining intensity was scored with four-point scale from 0 (no staining) to 3 (very intensive staining). Prostate and kidney cancer patients had been treated surgically and some of the cancers had relapsed after the surgery. In bladder cancer, association of serpinE2 with treatment response to neoadjuvant chemotherapy was evaluated. SerpinE2 expression was also measured in two prostate cancer cell lines with quantitative PCR and Western blotting. The serpinE2 staining was observed both in cancer cells and epithelial structures of benign tissues. The results showed that cancer tissue serpinE2 is not associated with relapse, treatment response or survival in prostate and bladder cancer patients. However, serpinE2 staining was more pronounced in prostate cancer tissues compared with benign tissues adjacent to cancer, and, surprisingly, the staining in such benign tissues was stronger in tissues from patients who developed metastases after surgery as compared to those without detectable metastases during 10.3-year (median) follow-up (p = 0.017). In addition, higher serpinE2 staining intensity was observed in higher grade bladder cancers (p = 0.034). In kidney cancer, on the other hand, serpinE2 staining intensity was significantly lower in patients whose cancer relapsed (p = 0.048), and high intensity predicted favourable disease-specific survival (p = 0.013). To conclude, serpinE2 is worth of further investigation in urological cancers. In prostate cancer, the possible field effect of cancer on serpinE2 in adjacent benign tissues could be examined more closely. In kidney cancer, the impact of serpinE2 on patient survival was inverse compared to transcript data in the Cancer Genome Atlas/the Human Protein Atlas database, and most other cancers. Thus, further validation studies need to be performed, and if the results hold true, serpinE2 staining could be used as part of a prognostic model predicting kidney cancer-specific survival.
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