Proteomic Profiling of Serum-Derived Exosomes from Ethnically Diverse Prostate Cancer Patients

Turay, David; Khan, Sharmin; Osterman, Carlos J. Díaz; Curtis, Matthew P.; Khaira, Balreet; Neidigh, Jonathan W.; Mirshahidi, Saied; Casiano, Carlos A.; Wall, Nathan R.

doi:10.3109/07357907.2015.1081921

Cited by 59 publications

(60 citation statements)

References 45 publications

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“…Although in the literature, there is already one study regarding exosomal proteomic analysis in ethnically diverse PCa patients, our study is different due to the following reasons: We have (a) characterized the exosomes from serum, (b) isolated exosomes by classical ultracentrifugation method, (c) quantified the exosomes by NTA, and (d) provided relative quantification of exosomal proteins (in terms of fold change). More importantly, in the present study, we have matched PCa with healthy individual for each race.…”

Section: Discussionmentioning

confidence: 99%

Exosome proteomic analyses identify inflammatory phenotype and novel biomarkers in African American prostate cancer patients

et al. 2019

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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.

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Section: Discussionmentioning

confidence: 99%

Exosome proteomic analyses identify inflammatory phenotype and novel biomarkers in African American prostate cancer patients

et al. 2019

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“…In recent years, there have been a multitude of studies investigating EVs as an alternative source of prostate‐derived proteins for the diagnosis and monitoring of PC, with a number of candidate biomarkers reported. One such study investigating blood EV profiles in PC patients strove to characterize differences in EV proteomes among ethnically diverse individuals . Plasma samples from men of African American, Caucasian, and Hispanic descent diagnosed with PC (as well as healthy controls) were subject to EV isolation using the ExoQuick isolation kit, with EV proteins then separated by 2D gel electrophoresis followed by in‐gel trypsin digestion and analysis via LC–MS/MS.…”

Section: Plasmamentioning

confidence: 99%

Tumor‐Derived Extracellular Vesicles as a Novel Source of Protein Biomarkers for Cancer Diagnosis and Monitoring

Ruhen

Meehan

2019

Proteomics

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“Liquid biopsies” have received attention as a complementary tool for traditional tissue biopsies that may enhance the spectrum of analysis for tumor‐derived factors. One such factor gaining prominence in the liquid biopsy field is extracellular vesicles (EVs), membrane‐bound nanovesicles which are secreted by cells into biofluids such as blood, urine, and saliva. EVs are released in both physiological and pathological conditions and can transport a variety of molecules, including proteins, metabolites, RNA, microRNAs, and DNA, to distant sites throughout the body. As such, they are emerging as a promising source of tumor biomarkers for the noninvasive diagnosis, prognosis, and monitoring of cancer patients. In particular, the wealth of tumor‐related information that can be gleaned from the EV proteomic cargo has become apparent through mass spectrometric analysis, which has provided new benchmarks for clinically focused biomarker research. In this review, the current achievements in the use of MS for identifying potential EV‐derived protein biomarkers of cancer are explored, and the techniques and challenges involved in this pursuit are summarized.

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“…In our research, we found increased serum exosome levels in patients with prostate and breast cancers as compared to disease free controls [53–55]. TEXs are prevalent in patient serum from multiple cancer types and protect labile biomarkers from degradation [42, 45, 48, 53–55]. …”

Section: Exosomesmentioning

confidence: 84%

Peritoneal carcinomatosis: limits of diagnosis and the case for liquid biopsy

et al. 2017

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Peritoneal Carcinomatosis (PC) is a late stage manifestation of several gastrointestinal malignancies including appendiceal, colorectal, and gastric cancer. In PC, tumors metastasize to and deposit on the peritoneal surface and often leave patients with only palliative treatment options. For colorectal PC, median survival is approximately five months, and palliative systemic therapy is able to extend this to approximately 12 months. However, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) with a curative intent is possible in some patients with limited tumor burden. In well-selected patients undergoing complete cytoreduction, median survival has been reported as high as 63 month. Identifying patients earlier who are either at risk for, or who have recently developed PC may provide them with additional treatment options such as CRS/HIPEC. PC is diagnosed late by imaging findings or often times during an invasive procedures such as laparoscopy or laparotomy. In order to improve the outcomes of PC patients, a minimally invasive, accurate, and specific PC screening method needs to be developed. By utilizing circulating PC biomarkers in the serum of patients, a “liquid biopsy,” may be able to be generated to allow a tailored treatment plan and early intervention. Exosomes, stable patient-derived nanovesicles present in blood, urine, and many other bodily fluids, show promise as a tool for the evaluation of labile biomarkers. If liquid biopsies can be perfected in PC, manifestations of this cancer may be more effectively treated, thus offering improved survival.

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Proteomic Profiling of Serum-Derived Exosomes from Ethnically Diverse Prostate Cancer Patients

Cited by 59 publications

References 45 publications

Exosome proteomic analyses identify inflammatory phenotype and novel biomarkers in African American prostate cancer patients

Exosome proteomic analyses identify inflammatory phenotype and novel biomarkers in African American prostate cancer patients

Tumor‐Derived Extracellular Vesicles as a Novel Source of Protein Biomarkers for Cancer Diagnosis and Monitoring

Peritoneal carcinomatosis: limits of diagnosis and the case for liquid biopsy

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