Abstract C098: CYR61 expression in prostate cancer patients at City of Hope
Authors: Ortiz-Hernandez Greisha L. , Ding Yuan Chun , Neuhausen Susan L. 
Published: September 2024

Abstract
In the US, African-American (AA) and Hispanic/Latino (H/L) men have higher rates of advanced prostate cancer (PCa), increased PCa-specific mortality, and are more likely to undergo metastasis than non-Hispanic White (NHW) men attributed to a lack of access to early screening, and a higher prevalence of risk factors such as obesity, diet, and genetic differences. Consequently, effective treatment of advanced PCa and elimination of racial and ethnic disparities for this malignancy require the identification of mechanisms of disease progression. In PCa, the cysteine-rich angiogenic inducer 61 (CYR61) contributes to malignant cell growth through interactions with extracellular ligands, such as integrins avb3 and a6b4. In previous studies, we have found that CYR61 is upregulated in metastatic PCa cell lines and knockdown of this protein significantly reduced metastatic cell proliferation, viability, prostasphere formation, and activation of the PI3/AKT pathway, indicating a potential utilization of CYR61 inhibition in the therapy of metastatic PCa. Interestingly, we have observed that in metastatic PCa cell models, IGF1 induction increased CYR61 protein expression. However, the correlation between PCa aggressiveness and levels of CYR61 in tumor-derived tissues from patients is poorly studied. Our goal with this study is to identify possible correlations in CYR61 expression that may reflect health disparities in PCa outcomes. We used in silico analyses from whole exome paired tumor/normal DNA sequencing and tumor RNA sequencing data available on 542 PCa cases in the City of Hope POSEIDON database to determine whether gene expression of CYR61 and IGF1 was correlated with genetic ancestry, Gleason score, and tumor purity. In univariate analyses, we found that H/L PCa cases had significantly higher levels of expression of CYR61 than NHW PCa cases (p = 0.043) and that both H/L and AA PCa cases had higher IGF1 expression levels, although only significant in AA (p=0.031). We also found that PCa patients with Gleason scores of 8 and higher had significantly lower expression of IGF1 than those with Gleason scores of 7 or less (p=0.006). Both CYR61 and IGF1 expression levels were significantly lower in those with luminal B (p=0.00000000053, p=0.000009, respectively) and with basal subtypes (p=0.00035, p=0.000069, respectively compared to luminal A subtype. Tumor purity was estimated by RNA-seq based on 141 genes specific to stroma and 141 genes specific to immune cells. CYR61 expression was significantly correlated with stromal and immune infiltration. These results suggest that reduced CYR61 expression is associated with more aggressive PCa. Additional analyses are ongoing to understand the interplay of variables of race and ethnicity, age, Gleason score, and tumor purity and to investigate outcomes of biochemical recurrence and death from PCa.
Citation Format: Greisha L. Ortiz-Hernandez, Yuan Chun Ding, Susan L. Neuhausen. CYR61 expression in prostate cancer patients at City of Hope [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C098.