Functionally distinct BMP1 isoforms show an opposite pattern of abundance in plasma from non-small cell lung cancer subjects and controls
Margaret K. R. Donovan, Yingxiang Huang, John E. Blume, Jian Wang, Daniel Hornburg, Shadi Ferdosi, Iman Mohtashemi, Sangtae Kim, Marwin Ko, Ryan W. Benz, Theodore L. Platt, Serafim Batzoglou, Luis A. Díaz, Omid C. Farokhzad, Asim Siddiqui
Abstract
Advancements in deep plasma proteomics are enabling high-resolution measurement of plasma proteoforms, which may reveal a rich source of novel biomarkers previously concealed by aggregated protein methods. Here, we analyze 188 plasma proteomes from non-small cell lung cancer subjects (NSCLC) and controls to identify NSCLC-associated protein isoforms by examining differentially abundant peptides as a proxy for isoform-specific exon usage. We find four proteins comprised of peptides with opposite patterns of abundance between cancer and control subjects. One of these proteins, BMP1, has known isoforms that can explain this differential pattern, for which the abundance of the NSCLC-associated isoform increases with stage of NSCLC progression. The presence of cancer and control-associated isoforms suggests differential regulation of BMP1 isoforms. The identified BMP1 isoforms have known functional differences, which may reveal insights into mechanisms impacting NSCLC disease progression.