Abstract C012: The expression of E-cadherin, B-catenin, N-cadherin, and phospho-Rb S249 as clinical informative biomarkers for the discrimination between indolent and aggressive forms of prostate cancer

Abstract

Abstract Prostate cancer (PCa) is the second most frequent malignancy in men worldwide1. However, a patient outcome depends on the type of tumor, which can be indolent or aggressive. The indolent PCa is characterized by slow tumor growth and favorable prognosis, whereas the aggressive form is rapidly spread and has high mortality3. However, after a positive biopsy, many of the patients undergo surgery or radiation because the doctor cannot be sure how quickly cancer might grow and spread6. This problem of discriminating between indolent and aggressive PCa has resulted in a significant problem of overtreating those patients with the indolent form of the disease. Thus, biomarkers that aid in the decision-making process and criteria regarding active surveillance in very low-, low-, and favorable intermediate-risk PCa face a large unmet need7. We aim to minimize the overtreatment of patients with indolent disease that will not require significant treatment and qualify for active surveillance as a long-term goal. For this purpose, we evaluated the clinical relevance of identified biomarkers that could be used in the clinic for the risk classification of indolent and aggressive PCa. We hypothesize that the combination of phospho-Rb S249, N-cadherin, E-cadherin, and β-catenin expression on PCa adenocarcinoma will serve as a clinical tool for the classification of aggressive tumors that induces metastasis or as indolent tumors that may qualify for active surveillance. As part of our methodology, we have conducted immunohistochemistry (N=182) against the expression of these biomarkers on PCa tumor microarrays (TMA’s). To assess if the expression of these biomarkers could correlate with any of the patient’s clinical parameters (stage, grade, tumor size, lymph nodes metastasis, metastasis to distant sites, Gleason score, and Gleason grade), we conducted correlation coefficient analyses. In addition, we created a linear regression model to determine if the combined proteins could precisely predict the patients' staging, grade, or Gleason score. Results have shown that the combination of phospho-Rb S249, N-cadherin, E-cadherin, and β-catenin had a precision of correctly predicting the staging of the patients by a 53.83%, and adding the TNM increases the accuracy to an 83.21% (N=413). Additionally, we identified that E-cadherin and β-catenin negatively correlated with the tumor size, grade, stage, Gleason grade, and Gleason score of the patients. N-cadherin and phospho-Rb S249 positively correlate with the tumor size, stage, and Gleason grade, and phospho-Rb S249 positively correlates with tumor size and stage. These results suggest that the expression of phospho-Rb S249, N-cadherin, E-cadherin, and β-catenin could potentially create a Prostate Proteomic Score (PPS) for the risk classification of indolent and aggressive PCa tumors. These findings will enhance the clinical decision of which patients should be treated or undergo active surveillance. Citation Format: Sheila Marie Valle-Cortes, Pedro Santiago, Gilberto Ruiz-Deya, Carlos Diaz-Osterman, Jaileene Perez-Morales. The expression of E-cadherin, B-catenin, N-cadherin, and phospho-Rb S249 as clinical informative biomarkers for the discrimination between indolent and aggressive forms of prostate cancer [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C012.