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

Author:

Dagley Laura F.12ORCID,Yousef Jumana12,Preaudet Adele12,Loving Andrea3,Webb Andrew I.12,Ernst Matthias45ORCID,Putoczki Tracy L.126ORCID

Affiliation:

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 gp130Y757F murine model of intestinal-type gastric cancer (IGC). We identified 30 proteins with significantly elevated expression in early gp130Y757F IGC and 12 proteins that were significantly elevated in late gp130Y757F 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 gp130Y757F 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.

Funder

CSL Ltd.

Ludwig Institute for cancer research

Sylvia and Charles Viertel Charitable Foundation Senior Medical Research Fellowship

Dyson Family

NHMRC Investigator Grant

Victorian State Government Operational Infrastructure Support Scheme

Publisher

MDPI AG

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