Identification of Serum Biomarkers to Monitor Therapeutic Response in Intestinal-Type Gastric Cancer

Laura F Dagley; Jumana Yousef; Adele Preaudet; Andrea Loving; Andrew I Webb; Matthias Ernst; Tracy L Putoczki

doi:10.3390/ijms25063129

Identification of Serum Biomarkers to Monitor Therapeutic Response in Intestinal-Type Gastric Cancer

Int J Mol Sci. 2024 Mar 8;25(6):3129. doi: 10.3390/ijms25063129.

Authors

Laura F Dagley^{1

2}, Jumana Yousef^{1

2}, Adele Preaudet^{1

2}, Andrea Loving³, Andrew I Webb^{1

2}, Matthias Ernst^{4

5}, Tracy L Putoczki^{1

2

6}

Affiliations

¹ The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia.
² Department of Medical Biology, The University of Melbourne, Melbourne, VIC 3052, Australia.
³ Ludwig Institute of Cancer Research, Melbourne, VIC 3052, Australia.
⁴ The Olivia Newton John Cancer Research Institute, Melbourne, VIC 3084, Australia.
⁵ School of Cancer Medicine, La Trobe University, Melbourne, VIC 3084, Australia.
⁶ Department of Surgery, The University of Melbourne, Melbourne, VIC 3052, Australia.

Abstract

There are a limited number of clinically useful serum biomarkers to predict tumor onset or treatment response in gastric cancer (GC). For this reason, we explored the serum proteome of the gp130^Y757F murine model of intestinal-type gastric cancer (IGC). We identified 30 proteins with significantly elevated expression in early gp130^Y757F IGC and 12 proteins that were significantly elevated in late gp130^Y757F IGC compared to age- and gender-matched wild-type mice. Within these signatures, there was an overlap of 10 proteins commonly elevated in both early- and late-stage disease. These results highlight the potential to identify serum biomarkers of disease stage. Since IGC in the gp130^Y757F model can be reversed following therapeutic inhibition of Interleukin (IL)-11, we explored whether the protein signatures we identified could be used to monitor tumor regression. We compared two different therapeutic modalities and found 5 proteins to be uniquely differentially expressed between control animals and animals halfway through treatment, with 10 differentially expressed at the end of treatment. Our findings highlight the potential to identify reliable biomarkers to track IGC tumor regression in response to treatment.

Keywords: Interleukin-11; biomarker; intestinal-type gastric cancer; mouse model; proteomics.

MeSH terms

Animals
Biomarkers
Biomarkers, Tumor
Cytokine Receptor gp130 / metabolism
Mice
Signal Transduction* / physiology
Stomach Neoplasms* / pathology

Substances

Cytokine Receptor gp130
Biomarkers
Biomarkers, Tumor

Grants and funding

This project was funded in part by a collaborative research agreement between CSL Ltd. and the Ludwig Institute for cancer research (to ME, TLP). This work was supported in part by a Sylvia and Charles Viertel Charitable Foundation Senior Medical Research Fellowship (to TLP). Generous philanthropic support was provided by the Dyson Family (to TLP). ME was supported by an NHMRC Investigator Grant. Funding from the Victorian State Government Operational Infrastructure Support Scheme is acknowledged.