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Mining proteomics data to extract post-translational modifications associated with gastric cancer

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Abstract

Gastric cancers are highly heterogeneous, deep-seated tumours associated with late diagnosis and poor prognosis. Post-translational modifications (PTMs) of proteins are known to be well-associated with oncogenesis and metastasis in most cancers. Several enzymes which drive PTMs have also been used as theranostics in cancers of the breast, ovary, prostate and bladder. However, there is limited data on PTMs in gastric cancers. Considering that experimental protocols for simultaneous analysis of multiple PTMs are being explored, a data-driven approach involving reanalysis of mass spectrometry-derived data is useful in cataloguing altered PTMs. We subjected publicly available mass spectrometry data on gastric cancer to an iterative searching strategy for fetching PTMs including phosphorylation, acetylation, citrullination, methylation and crotonylation. These PTMs were catalogued and further analyzed for their functional enrichment through motif analysis. This value-added approach delivered identification of 21,710 unique modification sites on 16,364 modified peptides. Interestingly, we observed 278 peptides corresponding to 184 proteins to be differentially abundant. Using bioinformatics approaches, we observed that majority of these altered PTMs/proteins belonged to cytoskeletal and extracellular matrix proteins, which are known to be perturbed in gastric cancer. The dataset derived by this mutiPTM investigation can provide leads to further investigate the potential role of altered PTMs in gastric cancer management.

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Data availability

The analysis data have been deposited to the ProteomeXchange Consortium (http://www.proteomecentral.proteomexchange.org) via the PRIDE partner repository with the dataset identifier PXD021887.

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Acknowledgements

We thank the Government of Karnataka for funding Yenepoya (Deemed to be University) under Biotechnology Skill Enhancement Programme (BiSEP). PR is a recipient of Senior Research Fellowship from the India Council of Medical Research (ICMR), Government of India. SKB is a recipient of the BINC Junior Research Fellowship from the Department of Biotechnology (DBT), Government of India. VM is a recipient of the Women Scientist A Fellowship from the Department of Science and Technology (DST), Government of India. RR is a recipient of the Young Scientist Award (YSS/2014/000607) from the Science and Engineering Research Board, Department of Science and Technology (DST), Government of India.

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Author notes

  1. Poornima Ramesh and Santosh Kumar Behera have Contributed equally to this work.

Authors and Affiliations

  1. Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to Be University), Mangalore, 575018, India

    Poornima Ramesh, Santosh Kumar Behera, Chinmaya Narayana Kotimoole, Varshasnata Mohanty, Rajesh Raju & T. S. Keshava Prasad

  2. Department of Surgical Oncology, Yenepoya Medical College, Yenepoya (Deemed to Be University), Mangalore, 575018, India

    Jalaluddin Akbar Kandel Codi

Authors
  1. Poornima Ramesh
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  2. Santosh Kumar Behera
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  3. Chinmaya Narayana Kotimoole
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  4. Varshasnata Mohanty
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  5. Rajesh Raju
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  6. T. S. Keshava Prasad
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Contributions

TSKP and JAKC conceived the study and designed the research workflow. PR, SKB and CNK conducted analysis. VM and RR contributed to the method, data analysis and manuscript writing. PR and SKB analyzed the data and wrote the manuscript. All the authors have read and approved the manuscript.

Corresponding authors

Correspondence to T. S. Keshava Prasad or Jalaluddin Akbar Kandel Codi.

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Ramesh, P., Behera, S.K., Kotimoole, C.N. et al. Mining proteomics data to extract post-translational modifications associated with gastric cancer. Amino Acids 55, 993–1001 (2023). https://doi.org/10.1007/s00726-023-03287-0

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