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Transcriptomic analysis of ovarian tumor pairs from primary and metastatic lesions

ABSTRACT: Ovarian cancer is one of the most lethal gynaecological malignancies among female population. The high mortality rate of this disease is due to its poor prognosis and most patients present at an advanced stage accompanied with metastasis. The frequent tumor recurrence rate associated with metastasis and chemoresistance are the major obstacles in clinical management of the disease. Different from other solid tumors, ovarian cancer perfers transcoelomic metastasis amd mounting evidence has suggested ovarian cancer patients who have peritoneal metastasis are usually poor prognosis and highly chemoresistant recurrence. In this study, we examined the differential gene expression profile between the primary tumors and their paired metastastic lesions with a view to discover novel target therapies in combating ovarian cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE178913 | GEO | 2021/06/26

REPOSITORIES: GEO

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Project description:Epithelial ovarian cancer is a very heterogeneous disease and remains the most lethal gynaecological malignancy in the Western world. Rational therapeutic approaches need to account for interpatient and intratumoral heterogeneity in treatment design. Detailed characterization of in vitro models representing the different histological and molecular subtypes is therefore imperative. Strikingly, from ~100 available ovarian cancer cell lines the origin and which subtype they represent is largely unknown. We have extensively and uniformly characterized 39 ovarian cancer cell lines (with mRNA/microRNA expression, exon sequencing, dose response curves for clinically relevant therapeutics) and obtained all available information on the clinical features and tissue of origin of the original ovarian cancer to refine the putative histological subtypes. From 39 ovarian cell lines, 14 were assigned as high-grade serous, four serous-type, one low-grade serous and 20 non-serous type. Three morphological subtypes (21 Epithelial, 7 Round, 12 Spindle) were identified that showed distinct biological and molecular characteristics, including overexpression of cell movement and migration-associated genes for the Spindle subtype. Clinical validation showed a clear association of the spindle-like tumors with metastasis, advanced stage, suboptimal debulking and poor prognosis. In addition, the morphological subtypes associated with the molecular C1-6 subtypes identified by Tothill et al. [1], Spindle clustered with C1-stromal subtype, Round with C5-mesenchymal and Epithelial with C4 subtype. We provide a uniformly generated data resource for 39 ovarian cancer cell lines, the ovarian cancer cell line panel (OCCP). This should be the basis for selecting models to develop subtype specific treatment approaches, which is very much needed to prolong the survival of ovarian cancer patients. Gene expression was measured for 32 ovarian cancer cell lines using the GeneChip Human Exon 1.0 ST Array (Affymetrix). Morphological subtypes were assigned based on cell morphology, size, growth pattern and proliferation rate during culturing of the cell lines.

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Transcriptomic analysis of ovarian tumor pairs from primary and metastatic lesions

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