O090 TRANSCRIPTOMICS OF BREAST CANCER TUMOUR AND NORMAL ADJACENT TUMOUR TISSUE REVEAL DIFFERENTIAL IMMUNE-ADIPOSE-CANCER GENE EXPRESSION

Abstract

Abstract Introduction Surgical-related immunity dysfunction in normal adjacent tumour (NAT) tissue of breast cancer (BC) patients is associated with BC recurrence. Characterising inflammation and immunosuppression in NAT tissue at the time of surgical excision of the tumour, using transcriptomics, may reveal a tissue phenotype more vulnerable to surgical-related immunity dysfunction. Methods RNA-Seq read counts from matched BC patient tumour and NAT tissues from the cancer genome atlas (TCGA) (n=54) and from University College Cork (UCC) & Cork University Hospital (CUH) biobank (n=10) were used. Differential gene expression was analysed using EdgeR and pathway analysis by Gene Set Enrichment Analysis using Hallmark gene sets. Immune cell subsets were deconvoluted using CIBERSORTx using the LM22 signature matrix. Genes were significantly different with a False Discovery Rate (FDR)<0.1 and pathways enriched with an FDR<0.25. Results Adipogenesis and IL6 JAK STAT3 signalling pathways were enriched in NAT and not in tumour tissue (FDR<0.25). Adipogenesis genes ADIPOQ, FABP4, CD36, LPL and PPARG and IL6 were significantly upregulated in NAT relative to tumour (FDR<0.1). Patients stratified on NAT expression of these genes, with higher expression had worse overall survival (OS)(p<0.05). There was no difference in patient OS, stratified on tumour expression of ADIPOQ and IL6. M2 macrophages were significantly increased in NAT relative to tumour(p<0.05). Patients with more M2 macrophages in tumours had significantly worse OS(p<0.05). There was no difference in OS for NAT tissue with more M2 macrophages. Conclusion Surgical-related immunity dysfunction in NAT breast tissue, may worsen postoperative immune-adipose-residual breast cancer cell interactions, contributing to poorer patient outcome.