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abstract
Background
It
is unclear whether the transcriptional subtypes of high grade serous
ovarian cancer (HGSOC) apply to high grade clear cell (HGCCOC) or high
grade endometrioid ovarian cancer (HGEOC). We aim to delineate
transcriptional profiles of HGCCOCs and HGEOCs.
Methods
We
used Agilent microarrays to determine gene expression profiles of 276
well annotated ovarian cancers (OCs) including 37 HGCCOCs and 66 HGEOCs.
We excluded low grade OCs as these are known to be distinct molecular
entities. We applied the prespecified TCGA and CLOVAR gene signatures
using consensus non-negative matrix factorization (NMF).
Results
We
confirm the presence of four TCGA transcriptional subtypes and their
significant prognostic relevance (p < 0.001) across all three
histological subtypes (HGSOC, HGCCOC and HGEOCs). However, we also
demonstrate that 22/37 (59%) HGCCOCs and 30/67 (45%) HGEOCs form 2
additional separate clusters with distinct gene signatures. Importantly,
of the HGCCOC and HGEOCs that clustered separately 62% and 65% were
early stage (FIGO I/II), respectively. These finding were confirmed
using the reduced CLOVAR gene set for classification where most early
stage HGCCOCs and HGEOCs formed a distinct cluster of their own. When
restricting the analysis to the four TCGA signatures (ssGSEA or NMF with
CLOVAR genes) most early stage HGCCOCs and HGEOC were assigned to the
differentiated subtype.
Conclusions
Using
transcriptional profiling the current study suggests that HGCCOCs and
HGEOCs of advanced stage group together with HGSOCs. However, HGCCOCs
and HGEOCs of early disease stages may have distinct transcriptional
signatures similar to those seen in their low grade counterparts.
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