Abstract B11: Proteomic analysis of serum-derived exosomes: Identification of novel protein signature associated with African-American prostate cancer

Abstract

Abstract African-American men face a stark prostate cancer (PCA)-related health disparity in the United States, with the highest incidence and mortality rate compared to all other races. African-American men are more frequently diagnosed with high Gleason grade PCA at a younger age and with a poorer prognosis. In the past three decades, there has been little improvement in reducing this health disparity, demanding additional and innovative measures. Here, we focused on the identification of novel serum exosome-based ‘protein signature' for potential use in the early detection and better prognosis of PCA in African-American men. Analysis of clinical serum samples showed that compared to healthy individuals, exosome concentration was increased by ~3.2 fold (p=0.047) in the sera of African-American men with PCA (Gleason score 7). Mass spectrometry based proteomic analysis of serum exosomal proteins showed 55 common proteins in African-American men with PCA (PAA) and normal African-American men without PCA (NAA). Interestingly, 7 unique proteins [Isoform 2 of Coiled-coil and C2 domain-containing protein 1A, Keratin type I cytoskeletal 10, UPF0728 protein C10orf53, DnaJ homolog subfamily C member 13, Prothrombin, Apolipoprotein(a) and Coiled-coil domain-containing protein 172] were present only in PAA, and not in NAA. The top upregulated proteins in PAA, as compared to NAA, included Keratin type II cytoskeletal 2 epidermal (64 fold), Serum amyloid P-component (39 fold), Keratin type II cytoskeletal 1 (13 fold), Keratin type I cytoskeletal 9 (12 fold), Isoform 2 of Filamin-A (2.6 fold), Isoform 3 of Vitamin D-binding protein (2.4 fold), Ig kappa chain V-II region Cum (2.4 fold) and Isoform 2 of Eukaryotic translation initiation factor 2-alpha kinase 4 (1.8 fold). The top downregulated proteins in PAA included Apolipoprotein A-I (0.04 fold), Complement component C8 alpha chain (0.07 fold), Plasminogen (0.08 fold), Complement component C7 (0.1 fold), and Isoform 2 of Inter-alpha-trypsin inhibitor heavy chain H4 (0.2 fold). Importantly, Ingenuity pathway analysis (IPA) showed that the proteins detected by proteomic analysis in PAA exosomes belonged to the acute-phase response signaling pathway proteins, which have been reported for their potential use as diagnostic biomarkers for PCA. Next, we compared proteins loaded in PAA serum exosomes with Gleason score-matched Caucasian PCA (PCC) serum exosomes. PAA and PCC exosomes shared 57 common proteins, while PAA serum exosomes showed six unique proteins (Isoform 2 of Coiled-coil and C2 domain-containing protein 1A, UPF0728 protein C10orf53, Ig kappa chain V-I region EU, Ig kappa chain V-II region Cum, DnaJ homolog subfamily C member 13, Coiled-coil domain-containing protein 172). Furthermore, top upregulated proteins in PAA, as compared to PCC, included Isoform 2 of Eukaryotic translation initiation factor 2-alpha kinase 4 (34 fold), Keratin type I cytoskeletal 10 (10 fold), SCO-spondin (5.3 fold), Serum amyloid P-component (4 folds) and Apolipoprotein(a) (3.9 fold). The top down regulated proteins in PAA, as compared to PCC, included Ig lambda chain V-I region WAH (0.02 fold), alpha-1B-glycoprotein (0.03 fold), Apolipoprotein A-I (0.03 fold), Complement component C8 alpha chain (0.06 fold) and Isoform 2 of Haptoglobin (0.09 fold). Overall, we have identified several unique and differentially expressed proteins in the serum exosomes of African-American men with PCA. These results also support further development and application of serum exosome-based proteomic signature for early detection and better prognosis of PCA in African- American men. Citation Format: Gagan Deep, Gatikrushna Panigrahi, Rakesh Singh, Kathleen Torkko, Adrie Bokhoven. Proteomic analysis of serum-derived exosomes: Identification of novel protein signature associated with African-American prostate cancer. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B11.