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

Roble G. Bedolla, Dimpy P Shah, Shih Bo Huang, Robert L. Reddick, Rita Ghosh, Addanki P Kumar

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalMolecular Carcinogenesis
DOIs
StatePublished - Jan 1 2019

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Receptor Protein-Tyrosine Kinases
African Americans
Prostatic Neoplasms
Prostate-Specific Antigen
Hispanic Americans
Androgen Receptors
Neoplasm Grading
Prostatectomy
Protein-Tyrosine Kinases
RON protein
Prostate
Obesity
Logistic Models
Immunohistochemistry
Regression Analysis
Cell Line
Neoplasms
Proteins

Keywords

  • androgen receptor
  • c-FLIP
  • prostate cancer
  • prostate cancer disparity
  • receptor tyrosine kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

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title = "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.",
keywords = "androgen receptor, c-FLIP, prostate cancer, prostate cancer disparity, receptor tyrosine kinase",
author = "Bedolla, {Roble G.} and Shah, {Dimpy P} and Huang, {Shih Bo} and Reddick, {Robert L.} and Rita Ghosh and Kumar, {Addanki P}",
year = "2019",
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T1 - Receptor tyrosine kinase recepteur d'origine nantais as predictive marker for aggressive prostate cancer in African Americans

AU - Bedolla, Roble G.

AU - Shah, Dimpy P

AU - Huang, Shih Bo

AU - Reddick, Robert L.

AU - Ghosh, Rita

AU - Kumar, Addanki P

PY - 2019/1/1

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N2 - 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.

AB - 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.

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