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Integrative network-based approaches identified systems-level molecular signatures associated with gallbladder cancer pathogenesis from gallstone diseases

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Abstract

Gallbladder cancer (GBC) is one of the most fatal malignancies of the biliary tract system and is ranked sixth among the neoplasms of the gastrointestinal tract. Gallstone disease (GSD) is considered the major risk factor for GBC. However, the underlying molecular mechanism of GBC pathogenesis from different stages of GSD is not yet clearly understood. We analyzed transcriptomic datasets of GBC with reference to GSD of three different follow-up periods, i.e., GBC vs. GSD3 (1–3 years), GBC vs. GSD5 (5–10 years), and GBC vs. GSD10 (more than 10 years). We identified overlapping and specific molecular signatures in GBC compared with GSD at three different follow-up periods. Using integrative network biology approaches, such as protein–protein interaction network analysis, transcriptional regulatory network analysis, and miRNA–target gene network analysis, we have identified a few hub genes. The hub genes identified from GBC vs. GSD3, GBC vs. GSD5, and GBC vs. GSD10 were directly or indirectly associated with cancer progression and initiation from GSD. Functional enrichment analysis indicated significant correlation between GSD and GBC pathogenesis. The identified hub genes can be used for future targeted validation to develop potential diagnostic, prognostic, or therapeutic biomarkers in GBC.

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Dataset availability

The datasets used for this study are available at NCBI-GEO database (SRA Accession No: SRP226150).

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Acknowledgements

PB would like to acknowledge the Department of Biotechnology, India, for providing the Ramalingaswami Re-entry Fellowship grant.

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Authors and Affiliations

  1. Department of Molecular Biology and Biotechnology, Tezpur University, Sonitpur, 784 028, India

    Nabanita Roy, Barasha Rani Dihingia & Pankaj Barah

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  1. Nabanita Roy
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  2. Barasha Rani Dihingia
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  3. Pankaj Barah
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Correspondence to Pankaj Barah.

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Communicated by Susmita Roy.

Corresponding editor: Susmita Roy

This article is part of the Topical Collection: Emergent dynamics of biological networks.

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Roy, N., Dihingia, B.R. & Barah, P. Integrative network-based approaches identified systems-level molecular signatures associated with gallbladder cancer pathogenesis from gallstone diseases. J Biosci 47, 31 (2022). https://doi.org/10.1007/s12038-022-00267-6

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