Spatially resolved transcriptomics of high-grade serous ovarian carcinoma
Elaine Stur,
Sara Corvigno,
Mingchu Xu,
Ken Chen,
Yukun Tan,
Sanghoon Lee,
Jinsong Liu,
Emily Ricco,
Daniel Kraushaar,
Patricia Castro,
Jianhua Zhang,
Anil K. Sood
Affiliations
Elaine Stur
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77054, USA
Sara Corvigno
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77054, USA
Mingchu Xu
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
Ken Chen
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
Yukun Tan
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
Sanghoon Lee
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
Jinsong Liu
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
Emily Ricco
Genomic and RNA Profiling Core, Baylor College of Medicine, Houston, TX 77030, USA
Daniel Kraushaar
Genomic and RNA Profiling Core, Baylor College of Medicine, Houston, TX 77030, USA
Patricia Castro
Pathology and Histology Core, Baylor College of Medicine, Houston, TX 77030, USA
Jianhua Zhang
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
Anil K. Sood
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77054, USA; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77054, USA; Corresponding author
Summary: Bulk and single-cell RNA sequencing do not provide full characterization of tissue spatial diversity in cancer samples, and currently available in situ techniques (multiplex immunohistochemistry and imaging mass cytometry) allow for only limited analysis of a small number of targets. The current study represents the first comprehensive approach to spatial transcriptomics of high-grade serous ovarian carcinoma using intact tumor tissue. We selected a small cohort of patients with highly annotated high-grade serous ovarian carcinoma, categorized them by response to neoadjuvant chemotherapy (poor or excellent), and analyzed pre-treatment tumor tissue specimens. Our study uncovered extensive differences in tumor composition between the poor responders and excellent responders to chemotherapy, related to cell cluster organization and localization. This in-depth characterization of high-grade serous ovarian carcinoma tumor tissue from poor and excellent responders showed that spatial interactions between cell clusters may influence chemo-responsiveness more than cluster composition alone.
