915 Molecular characterization of AXL in solid tumor malignancies using real-world data

Background The receptor tyrosine kinase AXL is aberrantly expressed in many cancer types and associated with epithelial-to-mesenchymal transition (EMT), poor prognosis, therapy resistance. To better understand the expression of this gene across specific disease subtypes, correlated pathways, how certain therapies potentially modulate expression, we investigated real-world clinical molecular data five solid tumor before after chemotherapy or immune checkpoint inhibitor (CPI) therapy. Methods Whole transcriptome exome sequencing were derived from patient specimens obtained either prior to treatment following CPI therapies. RNA reads mapped using STAR was normalized transcripts per million. DNA Novoalign variants called Freebayes Pindel. Clinical curated multiple sources, QC’d deidentified according standard protocols. Five diseases included: non-small cell lung (NSCLC, n=1181), ovarian (OV, n=300), urothelial carcinoma (UC, n=140), pancreatic ductal adenocarcinoma (PDAC, n=942), skin cutaneous melanoma (SKCM, n=157). PD-L1 positivity defined as ≥1% cells immunohistochemical staining at any intensity. Results mRNA levels highest PDAC followed by NSCLC, SKCM, UC OV. Within OV, higher tumors pre-treated relative untreated. For other types, had comparable untreated tumors. Copy number amplifications rare all (<3%) did not associate expression. Distinct subtypes several cancers displayed relatively high levels, including mesenchymal subtype OV stromal rich PDAC. also an EMT signature (rho=0.67). Further, (p<0.01), but where only a few positive.Oncogenic KRAS mutations NSCLC (p<0.001) lower (p=0.01). Loss KDM6A, known induce tumorigenesis PDAC, (p<0.01). Loss-of-function ARID1A, previously implicated sensitizing, (p<0.001). Conclusions Analyses datasets showed that upregulated settings well populations subtypes. Findings here should be validated independent datasets.