AXL signalling helps identify mesenchymal subtype ovarian cancer patients
“When we utilize gene expression molecular subtypes to stratify ovarian cancer, we can identify AXL and its related signalling network [as] a crucial player specifically in the [mesenchymal] subtype ovarian cancer,” said Dr Ruby Yun-Ju Huang from the Department of Obstetrics & Gynaecology at National University Hospital in Singapore.
Huang and her team performed a kinome enrichment analysis among GEMS using the Ov1538 ovarian cancer dataset (publicly available gene expression data of 1,538 ovarian cancer datasets). The researchers were able to identify AXL, a receptor tyrosine kinase that has GAS6 ligand. AXL was demonstrated to be the highest ranking kinase with poor prognosis in mesenchymal subtype tumours and cell lines.
AXL signature (AXLsig) consists of the top 30 genes that correlate with AXL that was derived from the gene expression microarray analysis of the Ov1538 dataset. The AXLsig was further correlated with GEMS, epithelial-mesenchymal transition (EMT) score, and clinical outcome of Ov1538 dataset.
Using the Ov1538 dataset, the AXLsig was found to be significantly overexpressed in mesenchymal GEMS. High AXLsig was associated with a worse overall survival (OS) with a hazard ratio (HR) of 1.26 (p=0.0096) at median cut-off and 1.58 (p=0.003) at lowest and highest quadrants cut-off.
The AXLsig showed a positive correlation with the ovarian-specific EMT score (Rho=+0.4148; p=5.23e–65). “[With a] high AXL score in the tumour, the tumour tends to have high EMT state,” said Huang.
Multivariate analysis was also performed to adjust according to the stage, age and grade of the tumours, which were also considered significant (HR, 1.51; p=0.0012).
“The AXL signalling pathway is also very important during the progression of ovarian cancer patients,” said Huang. The inhibition of AXL signalling will have a profound impact on cell survival particularly in mesenchymal ovarian cancer cells.“Therefore… if we can stratify ovarian cancer patients based on either the molecular subtype or AXL signalling, we probably can pick-up those subpopulations that would best benefit from AXL inhibition,” said Huang.