Intrinsic subtypes and prognostic implications in epithelial ovarian cancer
Abstract
Ovarian cancer is the seventh most common cancer in women globally, with approximately 240,000 new cases annually. Although a rare disease, it is the most lethal gynecologic malignancy. Unspecific symptoms result in late diagnosis and a generally poor prognosis. However, ovarian cancer is a heterogeneous disease comprising different disease entities, which is of importance in clinical decision-making as well as in research. This thesis describes explorative approaches to investigate the ovarian cancer heterogeneity in a hereditary ovarian cancer subset and in histopathological and molecular subtypes of ovarian cancer. In study I, a gene expression profile differentiating the rare subgroup of Lynch syndrome-associated ovarian cancer from a matched sporadic cohort was identified. The Lynch syndrome-related expression profile was associated with proliferation and cell death processes. An external dataset was used to refine the gene expression profile, but validation with immunohistochemical staining of key proteins did not reveal any differences between the hereditary and sporadic cases. A distinct cluster of hereditary serous and endometrioid cancers was seen, whereas clear cell carcinomas (OCCCs) clustered together, whether hereditary or sporadic. In study II, gene expression profiling of OCCCs revealed extensive inter-tumor heterogeneity. Targeted deep sequencing of 60 cancer-related genes in an OCCC cohort revealed frequent mutations of chromatin remodeling genes, including…
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Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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