Abstract 436: Prediction of aggressive disease in metastatic castration-resistant prostate cancer: The role of very small nuclear circulating tumor cells

Abstract

Abstract Background: Circulating tumor cells (CTCs) have arisen as a contemporary noninvasive prognostic biomarker for prostate cancer (PC). Previously, a subgroup of PC CTCs, with particularly small nuclei (<8.54 μm), were found to be correlated with poor prognosis and the emergence of visceral metastases (VM). This subgroup was named very-small nuclear CTCs (vsnCTCs). We proposed vsnCTCs as a biomarker of aggressive disease in metastatic castration-resistant PC (mCRPC). Previous Studies also showed that the disruption of emerin, a linker of nucleoskeleton and cytoskeleton complex proteins, increases the cancer cells' capacity of migration and invasion. We hypothesize that emerin mislocalization is potentially associated with vsnCTC formation and may be a critical step for metastasis. Methods: 35 blood samples were obtained from PC patients who failed first-line androgen deprivation therapy (ADT) and starting 2nd line treatment with abiraterone, enzalutamide, or taxane-based chemotherapy. Using our NanoVelcro CTC assay, we captured, subclassified, and enumerated the CTCs from patient samples with high-resolution imaging. Survival analyses were performed to exam the correlation between vsnCTC presence and patients’ prognosis. Concurrently, emerin staining was performed and the distribution and expression levels of emerin were analyzed in selected vsnCTC samples. Results: The presence of one or more vsnCTCs strongly correlated with inferior overall survival (OS), progression free survival (PFS), and time to VM (TTVM). We also observed lower emerin content in vsnCTCs compared to WBC, and more prominent emerin mislocalization in vsnCTCs compared to CTCs with larger nuclei. Conclusion: Our study strongly demonstrated the importance of morphologic characterization of CTCs and suggested that vsnCTC is a blood-borne biomarker for prediction of aggressive disease. Additionally, emerin mislocalization in vsnCTCs could be a potential biological pathway behind this morphologic phenomenon. Citation Format: Pin-Jung Chen, Yu Jen Jan, Pai-Chi Teng, Jie-Fu Chen, Shirley Cheng, Nu Yao, Mariana Reis-Sobreiro, Amber Lozano, Amy Gomez, Hsian-Rong Tseng, Michael Freeman, Edwin Posadas. Prediction of aggressive disease in metastatic castration-resistant prostate cancer: The role of very small nuclear circulating tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 436.