Project description: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.
Project description:High-grade serous ovarian cancer is the most aggressive histological type of epithelial ovarian cancer, which is characterized by a high frequency of somatic TP53 mutations. To provide a better understanding of the molecular mechanisms involved in the pathogenesis of these cancers and to develop a risk classification system, we conducted profiling of the copy number alterations present in these tumors. Thirty patients who were diagnosed as high-grade serous ovarian cancer were recruited in this study. Affymetrix SNP array were performed according to the manufacturer's directions on DNA extracted from high-grade serous ovarian cancer tissues or peripheral blood samples. The Japanese Serous Ovarian Cancer Study Group