Description

Analysis of single-cell RNAseq expression signatures in platinum-based chemotherapy responses of high-grade serous ovarian cancer

Kaiyang Zhang¹, Anniina Färkkilä^1,2, Katja Kaipio², Jun Dai³, Erdogan Erkan³, Rainer Lehtonen¹, Kaisa Huhtinen², Johanna Hynninen⁴, Seija Grénman⁴, Olli Carpén⁵, Sampsa Hautaniemi¹, Anna Vähärautio^3*

¹Research Programs Unit, Faculty of Medicine, Univ. of Helsinki, Finland; ²Department of Pathology, Univ. of Turku, Finland; ³Medicum, Faculty of Medicine, Univ. of Helsinki, Finland;

⁴Department of Obstetrics and Gynecology, Univ. of Turku and Turku Univ. Hospital, Finland;

⁵Helsinki Biobank, Univ. of Helsinki and Helsinki Univ. Hospital, Finland

^*Corresponding author

High-grade serous ovarian carcinoma (HGSOC) is the most common and lethal subtype of ovarian cancer. The first-line therapy consists of surgery and platinum-based chemotherapy. Regardless of favorable initial responses, most patients relapse and become resistant to chemotherapy leading to poor overall survival. To investigate intratumoral heterogeneity that primes chemoresistance, we utilize single-cell RNA-seq and in-house computational framework to analyze the expression data of single-cell transcriptomes obtained from HGSOC samples before and after chemotherapy. Our preliminary analysis from eight tumor specimens, comprising 367 single cells, identified 3 major cell populations that are characterized by tumoral (WFDC2, PAX8, EPCAM), immune (CD83, FCGR2A, FCER1G, PTPRC) and stromal (DCN, COL1A1, COL1A2, COL3A1) gene expression patterns. Clustering of the tumor cells revealed a subpopulation that expressed high levels of Epithelial-Mesenchymal Transition (EMT) - related genes LCN2, KLK6, S100A14, LAMC2, with majority of cells derived from a chemotherapy treated patient, suggesting putative involvement of EMT in tumor-cell chemotherapy responses. Our comprehensive analysis of single-cell RNA-seq data from a prospective HGSOC cohort reveals both inter- and intratumoral heterogeneity in samples before and after chemotherapy, and provides putative candidate targets for overcoming chemoresistance in HGSOC.