Exosome proteomic analyses identify inflammatory phenotype and novel biomarkers in African American prostate cancer patients
Abstract African American men face a stark prostate cancer (PCa)‐related health disparity, with the highest incidence and mortality rates compared to other races. Additional and innovative measures are warranted to reduce this health disparity. Here, we focused on the identification of a novel serum...
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| Format: | Article |
| Language: | English |
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Wiley
2019-03-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.1885 |
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| author | Gati K. Panigrahi Prakash P. Praharaj Hiroki Kittaka Asit R. Mridha Olen M. Black Rakesh Singh Roger Mercer Adrie van Bokhoven Kathleen C. Torkko Chapla Agarwal Rajesh Agarwal Zakaria Y. Abd Elmageed Hariom Yadav Santosh K. Mishra Gagan Deep |
| author_facet | Gati K. Panigrahi Prakash P. Praharaj Hiroki Kittaka Asit R. Mridha Olen M. Black Rakesh Singh Roger Mercer Adrie van Bokhoven Kathleen C. Torkko Chapla Agarwal Rajesh Agarwal Zakaria Y. Abd Elmageed Hariom Yadav Santosh K. Mishra Gagan Deep |
| author_sort | Gati K. Panigrahi |
| collection | DOAJ |
| description | Abstract African American men face a stark prostate cancer (PCa)‐related health disparity, with the highest incidence and mortality rates compared to other races. Additional and innovative measures are warranted to reduce this health disparity. Here, we focused on the identification of a novel serum exosome‐based “protein signature” for potential use in the early detection and better prognosis of PCa in African American men. Nanoparticle tracking analyses showed that compared to healthy individuals, exosome concentration (number/ml) was increased by ~3.2‐fold (P ˂ 0.05) in the sera of African American men with PCa. Mass spectrometry‐based proteomic analysis of serum exosomes identified seven unique and fifty‐five overlapping proteins (up‐ or downregulated) in African Americans with PCa compared to healthy African Americans. Furthermore, ingenuity pathway analyses identified the inflammatory acute‐phase response signaling as the top pathway associated with proteins loaded in exosomes from African American PCa patients. Interestingly, African American PCa E006AA‐hT cells secreted exosomes strongly induced a proinflammatory M2‐phenotype in macrophages and showed calcium response on sensory neurons, suggesting a neuroinflammatory response. Additionally, proteomic analyses showed that the protein Isoform 2 of Filamin A has higher loading (2.6‐fold) in exosomes from African Americans with PCa, but a lesser loading (0.6‐fold) was observed in exosomes from Caucasian men with PCa compared to race‐matched healthy individuals. Interestingly, TCGA and Taylor's dataset as well as IHC analyses of PCa tissue showed a lower Filamin A expression in tissues of PCa patients compared with normal subjects. Overall, these results support the usefulness of serum exosomes to noninvasively detect inflammatory phenotype and to discover novel biomarkers associated with PCa in African American men. |
| format | Article |
| id | doaj-art-9ee715367cbf46e3b1c3472eb37e4a08 |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2019-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-9ee715367cbf46e3b1c3472eb37e4a082025-01-31T08:47:43ZengWileyCancer Medicine2045-76342019-03-01831110112310.1002/cam4.1885Exosome proteomic analyses identify inflammatory phenotype and novel biomarkers in African American prostate cancer patientsGati K. Panigrahi0Prakash P. Praharaj1Hiroki Kittaka2Asit R. Mridha3Olen M. Black4Rakesh Singh5Roger Mercer6Adrie van Bokhoven7Kathleen C. Torkko8Chapla Agarwal9Rajesh Agarwal10Zakaria Y. Abd Elmageed11Hariom Yadav12Santosh K. Mishra13Gagan Deep14Cancer Biology Department Wake Forest Baptist Medical Center Winston‐Salem North CarolinaCancer Biology Department Wake Forest Baptist Medical Center Winston‐Salem North CarolinaDepartment of Molecular Biomedical Sciences, College of Veterinary Medicine NC State University Raleigh North CarolinaCancer Biology Department Wake Forest Baptist Medical Center Winston‐Salem North CarolinaCancer Biology Department Wake Forest Baptist Medical Center Winston‐Salem North CarolinaTranslational Science Laboratory, College of Medicine Florida State University Tallahassee FloridaTranslational Science Laboratory, College of Medicine Florida State University Tallahassee FloridaDepartment of Pathology University of Colorado Anschutz Medical Campus Aurora ColoradoDepartment of Pathology University of Colorado Anschutz Medical Campus Aurora ColoradoSchool of Pharmacy University of Colorado Anschutz Medical Campus Aurora ColoradoSchool of Pharmacy University of Colorado Anschutz Medical Campus Aurora ColoradoDepartment of Pharmaceutical Sciences Texas A&M Rangel College of Pharmacy College Station TexasDepartment of Internal Medicine‐Molecular Medicine and Department of Microbiology and Immunology Wake Forest Baptist Medical Center Winston-Salem North CarolinaDepartment of Molecular Biomedical Sciences, College of Veterinary Medicine NC State University Raleigh North CarolinaCancer Biology Department Wake Forest Baptist Medical Center Winston‐Salem North CarolinaAbstract African American men face a stark prostate cancer (PCa)‐related health disparity, with the highest incidence and mortality rates compared to other races. Additional and innovative measures are warranted to reduce this health disparity. Here, we focused on the identification of a novel serum exosome‐based “protein signature” for potential use in the early detection and better prognosis of PCa in African American men. Nanoparticle tracking analyses showed that compared to healthy individuals, exosome concentration (number/ml) was increased by ~3.2‐fold (P ˂ 0.05) in the sera of African American men with PCa. Mass spectrometry‐based proteomic analysis of serum exosomes identified seven unique and fifty‐five overlapping proteins (up‐ or downregulated) in African Americans with PCa compared to healthy African Americans. Furthermore, ingenuity pathway analyses identified the inflammatory acute‐phase response signaling as the top pathway associated with proteins loaded in exosomes from African American PCa patients. Interestingly, African American PCa E006AA‐hT cells secreted exosomes strongly induced a proinflammatory M2‐phenotype in macrophages and showed calcium response on sensory neurons, suggesting a neuroinflammatory response. Additionally, proteomic analyses showed that the protein Isoform 2 of Filamin A has higher loading (2.6‐fold) in exosomes from African Americans with PCa, but a lesser loading (0.6‐fold) was observed in exosomes from Caucasian men with PCa compared to race‐matched healthy individuals. Interestingly, TCGA and Taylor's dataset as well as IHC analyses of PCa tissue showed a lower Filamin A expression in tissues of PCa patients compared with normal subjects. Overall, these results support the usefulness of serum exosomes to noninvasively detect inflammatory phenotype and to discover novel biomarkers associated with PCa in African American men.https://doi.org/10.1002/cam4.1885biomarkerexosomeshealth disparityinflammationprostate cancer |
| spellingShingle | Gati K. Panigrahi Prakash P. Praharaj Hiroki Kittaka Asit R. Mridha Olen M. Black Rakesh Singh Roger Mercer Adrie van Bokhoven Kathleen C. Torkko Chapla Agarwal Rajesh Agarwal Zakaria Y. Abd Elmageed Hariom Yadav Santosh K. Mishra Gagan Deep Exosome proteomic analyses identify inflammatory phenotype and novel biomarkers in African American prostate cancer patients Cancer Medicine biomarker exosomes health disparity inflammation prostate cancer |
| title | Exosome proteomic analyses identify inflammatory phenotype and novel biomarkers in African American prostate cancer patients |
| title_full | Exosome proteomic analyses identify inflammatory phenotype and novel biomarkers in African American prostate cancer patients |
| title_fullStr | Exosome proteomic analyses identify inflammatory phenotype and novel biomarkers in African American prostate cancer patients |
| title_full_unstemmed | Exosome proteomic analyses identify inflammatory phenotype and novel biomarkers in African American prostate cancer patients |
| title_short | Exosome proteomic analyses identify inflammatory phenotype and novel biomarkers in African American prostate cancer patients |
| title_sort | exosome proteomic analyses identify inflammatory phenotype and novel biomarkers in african american prostate cancer patients |
| topic | biomarker exosomes health disparity inflammation prostate cancer |
| url | https://doi.org/10.1002/cam4.1885 |
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