Spatially resolved transcriptomics of high-grade serous ovarian carcinoma

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, 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. Overall design: High-grade serous ovarian carcinoma biopsy samples from 12 female patients were collected under a protocol approved by the Institutional Review Board of The University of Texas MD Anderson Cancer Center, and all patients provided written informed consent. The fresh frozen tumor tissues were obtained from the MD Anderson Gynecologic Tumor Bank. Patients underwent a standardized therapeutic approach following chemotherapy and surgery protocols established in the Department of Gynecology Oncology & Reproductive Medicine at MD Anderson. We selected six patients with poor response to NACT with carboplatin and paclitaxel and six patients with excellent response to NACT. The definition of poor response was stable or progressive disease after three to four cycles according to radiologic evaluation and/or suboptimal interval cytoreduction after NACT according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Excellent responders were those with complete response or only microscopic disease left at the time of interval surgery and/or pathologic analysis after interval surgery. We did not include replicates.