Harnessing the tissue and plasma lncRNA-peptidome to discover peptide-based cancer biomarkers

• Published in: Scientific reports 2019-08, Vol.9 (1), p.12322-17, Article 12322
• Main Authors: Chakraborty, Sajib, Andrieux, Geoffroy, Hasan, A. M. Mahmudul, Ahmed, Musaddeque, Hosen, Md. Ismail, Rahman, Tania, Hossain, M. Anwar, Boerries, Melanie
• Format: Article
• Language: English
• Subjects: 631/114/1314; 631/114/2784; 631/67/2195; 82/80; Adenocarcinoma; Adenocarcinoma - blood; Adenocarcinoma - genetics; Biomarkers; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Cancer; Cell Line; Colon; Colonic Neoplasms - blood; Colonic Neoplasms - genetics; Computer applications; Epithelium; Humanities and Social Sciences; Humans; Male; multidisciplinary; Neoplasms - blood; Neoplasms - genetics; Organ Specificity; Peptides; Peptides - blood; Plasma; Polypeptides; Prognosis; Prostate cancer; Prostatic Neoplasms - blood; Prostatic Neoplasms - genetics; Proteogenomics; Proteome - metabolism; Proteomes; RNA, Long Noncoding - blood; Science; Science (multidisciplinary); Tissues; Tumor cell lines
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-48774-1

Proteome-centric studies, although have identified numerous lncRNA-encoded polypeptides, lack differential expression analysis of lncRNA-peptidome across primary tissues, cell lines and cancer states. We established a computational-proteogenomic workflow involving re-processing of publicly available LC-MS/MS data, which facilitated the identification of tissue-specific and universally expressed (UExp) lncRNA-polypeptides across 14 primary human tissues and 11 cell lines. The utility of lncRNA-peptidome as cancer-biomarkers was investigated by re-processing LC-MS/MS data from 92 colon-adenocarcinoma (COAD) and 30 normal colon-epithelium tissues. Intriguingly, a significant upregulation of five lncRNA UExp-polypeptides in COAD tissues was observed. Furthermore, clustering of the UExp-polypeptides led to the classification of COAD patients that coincided with the clinical stratification, underlining the prognostic potential of the UExp-polypeptides. Lastly, we identified differential abundance of the UExp-polypeptides in the plasma of prostate-cancer patients highlighting their potential as plasma-biomarker. The analysis of lncRNA-peptidome may pave the way to identify effective tissue/plasma biomarkers for different cancer types.