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

Identification: Zhang, Kaiyang


Description

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

Kaiyang Zhang1, Anniina Färkkilä1,2, Katja Kaipio2, Jun Dai3, Erdogan Erkan3, Rainer Lehtonen1, Kaisa Huhtinen2, Johanna Hynninen4, Seija Grénman4, Olli Carpén5, Sampsa Hautaniemi1, Anna Vähärautio3*

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.

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