Proteomic variations of esophageal squamous cell carcinoma revealed by combining RNA-seq proteogenomics and G-PTM search strategy

• Main Authors: Pooja Ramesh, Vidhyavathy Nagarajan, Vartika Khanchandani, Vasanth Kumar Desai, Vidya Niranjan
• Format: Article
• Language: English
• Published: Elsevier 2020-08-01
• Series: Heliyon
• Subjects: Bioinformatics; Cancer research; Genetics; Oncology; Proteogenomics; Esophageal squamous cell carcinoma
• Online Access: http://www.sciencedirect.com/science/article/pii/S240584402031656X

Background: Cancer that arises from epithelial cells of the esophagus is called esophagus squamous cell carcinoma (ESCC) and is mostly observed in developing nations. Evaluation of cancer genomes and its regulation into proteins plays a predominant role in understanding the cancer progressions. Mass-spectrometry-based proteomics is a consequential tool to estimate proteomic variation and posttranslational modifications (PTMs) from standard protein databases. Post-translational modifications play a crucial role in protein folding and PTMs can be accounted for as a biological signal to interpret the structural changes and transition order of proteins. Functional validation of cancer-related mutations can explain the effects of mutations on genes and the identification of Oncogenes and tumor suppressor genes. Therefore, we present a study on protein variations to interpret the structural changes and transition order of proteins in ESCC carcinogenesis. Methodology: We are using a bottom-up proteomics approach with Galaxy-P framework and RNA sequence data analysis to generate the sample-specific databases containing details of RNA splicing and variant peptides. Once the database generated with information on variable modification, only the curated PTMs at specific positions are considered to perform spectral matching. Proteogenomics mapping was performed to identify protein variations in ESCC. Results: RNA-sequence proteogenomics with G-PTM (Global Post-Translational Modification) searching strategy has revealed proteomic events including several peptides that contain single amino acid variations, novel splice junction peptides and posttranslationally modified peptides. Proteogenomic mapping exhibited the splice junction peptides mapped predominantly for Malic enzyme exon type (ME-3) and MCM7 protein-coding genes that promote cancer progression, found to be exhibited in ESCC samples. Approximately 25 ± types of PTM modifications were recorded, and Protein Phosphorylation was largely noted. Conclusion: ESCC cancer prognosis at the molecular level enables a better understanding of cancer carcinogenesis and protein modifications can be used as potential biomarkers.