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Discovering biomarkers for hormone-dependent tumors: in silico study on signaling pathways implicated in cell cycle and cytoskeleton regulation

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Abstract

Malignancies dependent on hormone homeostasis include breast, ovary, cervical, prostate, testis and uterine tumors. Hormones are involved in signal transduction which orchestrate processes, such as apoptosis, proliferation, cell cycle or cytoskeleton organization. Currently, there is a need for novel biomarkers which would help to diagnose cancers efficiently. In this study, the genes implicated in signaling that is important in hormone-sensitive carcinogenesis were investigated regarding their prognostic significance. Data of seven cancer cohorts were collected from FireBrowse. 54 gene sets implicated in specific pathways were browsed through MSig database. Profiling was assessed via Monocle3, while gene ontology through PANTHER. For confirmation, correlation analysis was performed using WGCNA. Protein–protein networks were visualized via Cytoscape and impact of genes on survival, as well as cell cycle or cytoskeleton-related prognostic signatures, was tested. Several differences in expression profile were identified, some of them allowed to distinguish histology. Functional annotation revealed that various regulation of cell cycle, adhesion, migration, apoptosis and angiogenesis underlie these differences. Clinical traits, such as histological type or cancer staging, were found during evaluation of module-trait relationships. Of modules, the TopHubs (COL6A3, TNR, GTF2A1, NKX3-1) interacted directly with, e.g., PDGFB, ITGA10, SP1 or AKT3. Among TopHubs and interacting proteins, many showed an impact on hazard ratio and affected the cell cycle or cytoskeleton-related prognostic signatures, e.g., COL1A1 or PDGFB. In conclusion, this study laid the foundation for further hormone-sensitive carcinogenesis research through identification of genes which prove that crosstalk between cell cycle and cytoskeleton exists, opening avenues for future therapeutic strategies.

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Data availability

Publicly available datasets were analyzed in this study. This data can be found here: https://gdac.broadinstitute.org/ (accessed on 16 January 2021).

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Acknowledgments

The authors did not receive support from any organization for the submitted work.

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This research received no external funding. The authors have no relevant financial or non-financial interests to disclose.

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  1. Klaudia Waszczykowska and Karolina Prażanowska are Co-first authors.

  2. Żaneta Kałuzińska and Damian Kołat are Co-second authors.

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  1. Faculty of Biomedical Sciences, Medical University of Lodz, 90-752, Lodz, Poland

    Klaudia Waszczykowska & Karolina Prażanowska

  2. Department of Molecular Carcinogenesis, Medical University of Lodz, 90-752, Lodz, Poland

    Żaneta Kałuzińska, Damian Kołat & Elżbieta Płuciennik

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  1. Klaudia Waszczykowska
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Contributions

DK and ŻK conceptualized the article. KW, KP, ŻK and DK established the methodology. KW, KP, ŻK and DK was responsible for software. EP supervised the article. DK and ŻK visualized the results. KW and KP wrote the original draft. KW, KP, DK, ŻK and EP reviewed and edited the article. All authors read and approved the final manuscript.

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Correspondence to Żaneta Kałuzińska.

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Communicated by Shuhua Xu.

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Waszczykowska, K., Prażanowska, K., Kałuzińska, Ż. et al. Discovering biomarkers for hormone-dependent tumors: in silico study on signaling pathways implicated in cell cycle and cytoskeleton regulation. Mol Genet Genomics 297, 947–963 (2022). https://doi.org/10.1007/s00438-022-01900-7

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