iScience (Jan 2023)
Identifying biomarkers of differential chemotherapy response in TNBC patient-derived xenografts with a CTD/WGCNA approach
- Varduhi Petrosyan,
- Lacey E. Dobrolecki,
- Lillian Thistlethwaite,
- Alaina N. Lewis,
- Christina Sallas,
- Ramakrishnan R. Srinivasan,
- Jonathan T. Lei,
- Vladimir Kovacevic,
- Predrag Obradovic,
- Matthew J. Ellis,
- C. Kent Osborne,
- Mothaffar F. Rimawi,
- Anne Pavlick,
- Maryam Nemati Shafaee,
- Heidi Dowst,
- Antrix Jain,
- Alexander B. Saltzman,
- Anna Malovannaya,
- Elisabetta Marangoni,
- Alana L. Welm,
- Bryan E. Welm,
- Shunqiang Li,
- Gerburg M. Wulf,
- Olmo Sonzogni,
- Chen Huang,
- Suhas Vasaikar,
- Susan G. Hilsenbeck,
- Bing Zhang,
- Aleksandar Milosavljevic,
- Michael T. Lewis
Affiliations
- Varduhi Petrosyan
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
- Lacey E. Dobrolecki
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA
- Lillian Thistlethwaite
- Quantitative and Computational Biosciences Program, Baylor College of Medicine, Houston, TX 77030, USA
- Alaina N. Lewis
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA
- Christina Sallas
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA
- Ramakrishnan R. Srinivasan
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA
- Jonathan T. Lei
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA
- Vladimir Kovacevic
- School of Electrical Engineering, University of Belgrade, Belgrade, Serbia
- Predrag Obradovic
- School of Electrical Engineering, University of Belgrade, Belgrade, Serbia
- Matthew J. Ellis
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
- C. Kent Osborne
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
- Mothaffar F. Rimawi
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
- Anne Pavlick
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA
- Maryam Nemati Shafaee
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA
- Heidi Dowst
- Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
- Antrix Jain
- Mass Spectrometry Proteomics Core, Baylor College of Medicine, Houston, TX 77030, USA
- Alexander B. Saltzman
- Mass Spectrometry Proteomics Core, Baylor College of Medicine, Houston, TX 77030, USA
- Anna Malovannaya
- Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Mass Spectrometry Proteomics Core, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA
- Elisabetta Marangoni
- Curie Institute, Paris, France
- Alana L. Welm
- Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA
- Bryan E. Welm
- Department of Surgery, University of Utah, Salt Lake City, UT 84112, USA; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA
- Shunqiang Li
- Division of Oncology, Washington University, St. Louis, MO 63130, USA
- Gerburg M. Wulf
- Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
- Olmo Sonzogni
- Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
- Chen Huang
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA
- Suhas Vasaikar
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA
- Susan G. Hilsenbeck
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
- Bing Zhang
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Quantitative and Computational Biosciences Program, Baylor College of Medicine, Houston, TX 77030, USA
- Aleksandar Milosavljevic
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Quantitative and Computational Biosciences Program, Baylor College of Medicine, Houston, TX 77030, USA
- Michael T. Lewis
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA; Department of Radiology, Baylor College of Medicine, Houston, TX, USA; Corresponding author
- Journal volume & issue
-
Vol. 26,
no. 1
p. 105799
Abstract
Summary: Although systemic chemotherapy remains the standard of care for TNBC, even combination chemotherapy is often ineffective. The identification of biomarkers for differential chemotherapy response would allow for the selection of responsive patients, thus maximizing efficacy and minimizing toxicities. Here, we leverage TNBC PDXs to identify biomarkers of response. To demonstrate their ability to function as a preclinical cohort, PDXs were characterized using DNA sequencing, transcriptomics, and proteomics to show consistency with clinical samples. We then developed a network-based approach (CTD/WGCNA) to identify biomarkers of response to carboplatin (MSI1, TMSB15A, ARHGDIB, GGT1, SV2A, SEC14L2, SERPINI1, ADAMTS20, DGKQ) and docetaxel (c, MAGED4, CERS1, ST8SIA2, KIF24, PARPBP). CTD/WGCNA multigene biomarkers are predictive in PDX datasets (RNAseq and Affymetrix) for both taxane- (docetaxel or paclitaxel) and platinum-based (carboplatin or cisplatin) response, thereby demonstrating cross-expression platform and cross-drug class robustness. These biomarkers were also predictive in clinical datasets, thus demonstrating translational potential.
