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MST1R (RON) expression is a novel prognostic biomarker for metastatic progression in breast cancer patients

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Abstract

Purpose

This study evaluates the prognostic significance of MST1R (RON) expression in breast cancer with respect to disease progression, long-term survival, subtype, and association with conventional prognostic factors.

Methods

The approach includes interrogation of survival and tumor staging with paired MST1R RNA expression from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Protein expression evaluation was performed using immunohistochemistry (IHC) staining of MST1R on breast cancer tissue samples from the Cancer Diagnosis Program Breast Cancer Progression tissue microarray and locally obtained breast tumor tissue samples analyzed with paired survival, metastasis, and subtype.

Results

Data from TCGA (n = 774) show poorer relapse-free survival (RFS) in patients with high MST1R expression (P = 0.32) and no difference in MST1R expression based on tumor stage (P = 0.77) or nodal status (P = 0.94). Patients in the GEO-derived Kaplan–Meier Plotter microarray dataset demonstrate the association of MST1R and poorer overall survival (n = 1402, P = 0.018) and RFS in patients receiving chemotherapy (n = 798, P = 0.041). Patients with high MST1R expression display worse overall survival (P = 0.01) and receiver operator characteristic (ROC) analysis demonstrate the predictive capacity of increased MST1R with early death (P = 0.0017) in IHC-stained samples. Paired IHC-stained breast tumor samples from the primary versus metastatic site show MST1R expression is associated with metastatic progression (P = 0.032), and ROC analysis supports the predictive capacity of MST1R in metastatic progression (P = 0.031). No associations of MST1R with estrogen receptor (ER), progesterone receptor (PR), both ER and PR, HER2 positivity, or triple-negativity were found (P = 0.386, P = 0.766, P = 0.746, P = 0.457, P = 0.947, respectively).

Conclusions

MST1R expression has prognostic value in breast cancer with respect to survival and metastatic progression. MST1R expression is not associated with tumor stage, nodal status, or subtype.

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Acknowledgements

We would like to thank Phillip Dexheimer and Mario Pujato, PhD, for help with PAM50 gene clustering and subtype assignment. This study was funded by VA Merit Award 1IO1BX000803 (SEW), F31CA228373 (BGH), T32CA117846 (SEW and CAW), Marlene Harris Ride Cincinnati Awards (VT and SEW), and a Career Development Award from the Biomedical Laboratory Research and Development Service of the US Department of Veterans Affairs (IK2 BX004360)

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Authors and Affiliations

  1. Department of Cancer Biology, College of Medicine, University of Cincinnati, Cincinnati, OH, 45267, USA

    Brian G. Hunt, Jennifer R. Bourn & Susan E. Waltz

  2. Department of Radiation Oncology, College of Medicine, University of Cincinnati, Cincinnati, OH, 45267, USA

    Christina A. Wicker & Vinita Takiar

  3. Department of Internal Medicine, Hematology and Oncology Division, College of Medicine, University of Cincinnati, Cincinnati, OH, 45267, USA

    Elyse E. Lower

  4. Research Service, Cincinnati Veteran’s Affairs Medical Center, Cincinnati, OH, 45220, USA

    Vinita Takiar & Susan E. Waltz

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  1. Brian G. Hunt
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Correspondence to Susan E. Waltz.

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We declare that there are no potential conflicts of interest.

Ethical approval

Retrospective and archived sample studies presented herein comply with ethical standards implemented by the University of Cincinnati according to the specific requirements for human subjects testing in the United States.

Research involving Human Participants and/or Animals

Human participants: Samples obtained from human subjects were anonymized and de-identified prior to our acquisitionAnimals were not used in this study.

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As is common practice at the University of Cincinnati and the Cooperative Human Tissue Network, Institutional Review Board (IRB) review took place and IRB protocol deemed unnecessary due to the anonymized and de-identified nature prior to acquisition of samples.

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Hunt, B.G., Wicker, C.A., Bourn, J.R. et al. MST1R (RON) expression is a novel prognostic biomarker for metastatic progression in breast cancer patients. Breast Cancer Res Treat 181, 529–540 (2020). https://doi.org/10.1007/s10549-020-05653-y

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  • DOI: https://doi.org/10.1007/s10549-020-05653-y

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