Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy

Oesophageal adenocarcinoma (OAC) is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigated whole genome, and where possible transcriptomic and methylation data from 115 OAC patients mostly from the DOCTOR phase II clinical trial (ANZCTR-ACTRN12609000665235). We identified genomic features associated with poorer overall survival, such as the APOBEC mutational and RS3-like rearrangement signatures. We also showed that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. Transcriptomic analysis categorised patients into four immune clusters correlated with survival. The immune suppressed cluster was associated with worse survival, enriched with myeloid-derived cells, and an epithelial-mesenchymal transition signature. The immune hot cluster was associated with better survival, enriched with lymphocytes, myeloid-derived cells, and an immune signature including CCL5, CD8A, and NKG7. The immune clusters highlight patients who may respond to immunotherapy and thus may guide future clinical trials. This study used 34 public 450K methylation arrays (GSE72874) and 38 new EPIC arrays in this submission. Normalized data of all 72 samples provided plus raw idat for the new 38 EPIC arrays.