Line Victoria Moen1, Håkon Ramberg2, Sen Zhao3, Helene Hartvedt Grytli2, Anita Sveen3, Viktor Berge4, Rolf I Skotheim3, Kristin Austlid Taskén5, Bjørn Steen Skålhegg6. 1. Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. 2. Department of Tumor Biology, Institute of Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway. 3. Department of Molecular Oncology, Institute of Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway; Medical Faculty, Center for Cancer Biomedicine, University of Oslo University Hospital, Oslo, Norway. 4. Department of Urology, Oslo University Hospital, Oslo, Norway. 5. Department of Tumor Biology, Institute of Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 6. Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. Electronic address: b.s.skalhegg@medisin.uio.no.
Abstract
BACKGROUND: Today overtreatment of indolent prostate cancers and undertreatment of aggressive prostate cancer are a major concern for patients, their families, and the health care system. New biomarkers distinguishing indolent and aggressive prostate cancer are needed to improve precision medicine. In prostate cancer, protein kinase A (PKA) is known to activate the androgen receptor and published data indicate that PKA subunits can act as predictive markers for response to radiation and chemotherapy. We have previously shown that the catalytic subunit, Cβ2, of PKA is up-regulated in prostate cancer and we would in this study investigate the potential of Cβ2 to become a prognostic biomarker in prostate cancer. METHODS: Data were sampled from a total of 241 patients from 3 independent cohorts. We measured and compared Cβ2 messenger RNA (mRNA) levels in prostate tumor and nontumor samples (n = 22), and exon levels in a cohort of 50 tumor samples, as well as acquiring mRNA data from the publicly available database The cancer genome atlas (n = 169). RESULTS: Cβ2 mRNA was up-regulated in prostate cancer in all 3 cohorts, measured by 3 different methods. Furthermore, the relative Cβ2 mRNA expression levels were lower in prostate cancer samples with Gleason score 8 to 10 compared with samples with Gleason score<8 (P = 0.004). Finally, low expression of Cβ2 mRNA in prostate cancer biopsies correlated with poor survival (hazard ratio = 0.20; 95% CI: 0.048-0.86; P = 0.031), adjusted for risk group and age. CONCLUSIONS: We suggest that Cβ2 mRNA expression may be used as a biomarker together with established prognostic markers to more precisely predict aggressiveness in patients diagnosed with prostate cancer.
BACKGROUND: Today overtreatment of indolent prostate cancers and undertreatment of aggressive prostate cancer are a major concern for patients, their families, and the health care system. New biomarkers distinguishing indolent and aggressive prostate cancer are needed to improve precision medicine. In prostate cancer, protein kinase A (PKA) is known to activate the androgen receptor and published data indicate that PKA subunits can act as predictive markers for response to radiation and chemotherapy. We have previously shown that the catalytic subunit, Cβ2, of PKA is up-regulated in prostate cancer and we would in this study investigate the potential of Cβ2 to become a prognostic biomarker in prostate cancer. METHODS: Data were sampled from a total of 241 patients from 3 independent cohorts. We measured and compared Cβ2 messenger RNA (mRNA) levels in prostate tumor and nontumor samples (n = 22), and exon levels in a cohort of 50 tumor samples, as well as acquiring mRNA data from the publicly available database The cancer genome atlas (n = 169). RESULTS: Cβ2 mRNA was up-regulated in prostate cancer in all 3 cohorts, measured by 3 different methods. Furthermore, the relative Cβ2 mRNA expression levels were lower in prostate cancer samples with Gleason score 8 to 10 compared with samples with Gleason score<8 (P = 0.004). Finally, low expression of Cβ2 mRNA in prostate cancer biopsies correlated with poor survival (hazard ratio = 0.20; 95% CI: 0.048-0.86; P = 0.031), adjusted for risk group and age. CONCLUSIONS: We suggest that Cβ2 mRNA expression may be used as a biomarker together with established prognostic markers to more precisely predict aggressiveness in patients diagnosed with prostate cancer.