Abstract 5378: A comparative analysis on the expression of PSA protein in serum and PSA mRNA in circulating tumor cells in prostate cancer
Authors: Cho Hyungseok , Han Ki-Ho , Chung Jae-Seung 
Published: September 2020

Introduction Unlike other cancers, prostate cancer has a distinguished biomarker for diagnosis and prognosis which is known as prostate specific antigen (PSA) protein in serum. In the early stage of prostate cancer, PSA protein in serum is highly expressed from primary tumor sites and thereby, the expression of PSA protein can be used in prognosis of prostate cancer during whole progression. However, due to low specificity of serum PSA protein, it raised concerns in over-diagnosis. Due to the advantages of noninvasive, real-time and pain-free for patients, circulating tumor cells (CTCs) is being researched as complementary alternative biomarkers for clinical and molecular analysis of cancer. Some studies reported that the levels of PSA protein and PSA mRNA in prostate cancer tissue are proportional to each other. Other studies showed that the expression level of PSA mRNA in peripheral blood and biochemical recurrence of PSA protein in serum are significant relationship. However, the relevance between PSA protein in serum and PSA mRNA in CTCs has not been clearly researched. In this study, we first report the relevance of the expression levels of PSA protein in serum and PSA mRNA in CTCs.

Experimental method and analysis Prostate cancer patients were recruited from healthy donor (HD, n=5), local with non-metastatic stage (n=25), metastatic hormone sensitive prostate cancer (mHSPC, n=9) and metastatic castration-resistance prostate cancer (mCRPC, n=28). CTCs were isolated by high efficiency and purity using microfluidic technology based on lateral magnetophoresis, developed in our laboratory. Total mRNA was extracted from isolated CTC and the expression level of PSA mRNA in CTCs was measured by droplet digital PCR (ddPCR). Then, the expression levels of PSA protein (ng/ml) in serum and PSA mRNA (copies/µl) in CTCs were compared by statistical analysis.

Results and discussion The expression of PSA mRNA in CTCs was observed in 40% of localized cancer, 55.56% of mHSPC, 89.29% of mCRPC patients and 0% of HD group. It indicates that the detection rate of PSA mRNA increases with stage of prostate cancer. The expression level of PSA mRNA in CTCs also increased from localized to metastatic stages. Interestingly, it increased very rapidly in mHSPC and mCRPC stages. In 7 of the blood samples of localized stage, the expression levels of PSA mRNA in CTCs were detected and they were not related to serum PSA protein. In mHSPC and mCRPC stage, the expression levels of PSA mRNA in CTCs were respectively detected in 5 and 25 samples, implicating that their expression levels are significantly related to the level of PSA protein in serum.

Conclusions This result shows that the expression level of PSA mRNA in CTCs could be used as a new marker along with serum PSA protein in metastatic stages of prostate cancer, and that high-quality CTCs can be used as complementary alternative biomarkers for precision medicine in prostate cancer.

Citation Format: Hyungseok Cho, Ki-Ho Han, Jae-Seung Chung. A comparative analysis on the expression of PSA protein in serum and PSA mRNA in circulating tumor cells in prostate cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5378.