Receptor tyrosine kinase recepteur d'origine nantais as predictive marker for aggressive prostate cancer in African Americans

Abstract

Published evidence shows a correlation between several molecular markers and prostate cancer (PCa) progression including in African Americans (AAs) who are disproportionately affected. Our early detection efforts led to the identification of elevated levels of antiapoptotic protein, c‐FLIP and its upstream regulatory factors such as androgen receptor (AR), recepteur d'origine nantais (RON), a receptor tyrosine kinase in human prostate tumors. The primary objective of this study was to explore whether these markers play a role in racial disparities using immunohistochemistry in prostatectomy samples from a cohort of AA, Hispanic Whites (HWs), and non‐Hispanic Whites (NHWs). Bivariable and multivariable logistic regression analyses were used to identify a statistical association between molecular markers, possible correlation with risk factors including race, obesity, prostate‐specific antigen (PSA) and disease aggressiveness. Further, changes in the levels and expression of these molecular markers were also evaluated using human PCa cell lines. We found significantly elevated levels of RON ( P = 0.0082), AR ( P = 0.0001), c‐FLIP ( P = 0.0071) in AAs compared with HWs or NHWs. Furthermore, a higher proportion of HW and NHWs had a high Gleason score (>6) but not PSA as compared to AAs ( P = 0.032). In summary, our findings suggest that PSA was important in predicting aggressive disease for the cohort overall; however, high levels of RON may play a role in predisposing AA men to develop aggressive disease. Future research is needed using large datasets to confirm these findings and to explore whether all or any of these markers could aid in race‐specific stratification of patients for treatment.

Evidence for 2-Methoxyestradiol-Mediated Inhibition of Receptor Tyrosine Kinase RON in the Management of Prostate Cancer

“…Further, these findings suggest that RON activity can be measured non-invasively and plasma levels of MSP can potentially be developed as a marker of aggressive cancer. Recently, we have reported elevated protein levels of RON in African American (AA) patients compared to Hispanic Whites (HW) and non-Hispanic Whites (NHW) combined [ 28 ]. Based on above observations, we measured levels of MSP in plasma samples from AAs and HWs and NHWs.…”

“…We hypothesize that MSP may allow tumors to grow in a non-androgen dependent pathway. Furthermore, serum from AA patients showed significantly elevated levels of MSP compared to PCa is the most commonly diagnosed cancer (30%) in AAs and contributes to 15% of cancer related deaths [ 1 , 28 , 56 , 57 , 58 ]. While 1 of 7 black men develop and 1 of 25 die from PCa, these statistics are distinctly different from white men of European descent with PCa diagnosis (1 in 9 for incidence and in 1 of 45 for death).…”

Targeting RON receptor tyrosine kinase for treatment of advanced solid cancers: antibody–drug conjugates as lead drug candidates for clinical trials

“…9 Since then, increased RON expression has been documented in various types of cancer including those from colorectal, lung, breast, pancreatic, and others. [6][7][8][9][10][11][12][13] A systematic analysis using tumor tissue microarrays demonstrates that RON overexpression at the rate of 30% and above occurs in tumors including colorectal, breast, and pancreatic cancers. 6 Recently, increased RON expression has also been documented in bladder and prostate cancers.…”

Гормональные Маркеры Рака Предстательной Железы И Лечение Больных

“…Mìžnarodnij endokrinologìčnij žurnal, ISSN 2224-0721 (print), ISSN 2307-1427 (online) Оригінальні дослідження /Original Researches/ ся вивченою недостатньо [11]. Потребує подальшого з'ясування характер динаміки маркерів при РПЗ на тлі гормональної антиандрогенної терапії [12,13].…”