Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy
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ABSTRACT:
PROVIDER: PRJNA826110 | ENA |
REPOSITORIES: ENA
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Project description: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.
2023-04-24 | GSE200707 | GEO
Project description:Oesophageal adenocarcinoma is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigate whole genome, transcriptomic and methylation data from 115 oesophageal adenocarcinoma patients mostly from the DOCTOR phase II clinical trial (Australian New Zealand Clinical Trials Registry-ACTRN12609000665235), with exploratory analysis pre-specified in the study protocol of the trial. We report genomic features associated with poorer overall survival, such as the APOBEC mutational and RS3-like rearrangement signatures. We also show that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. Transcriptomic analysis categorises patients into four immune clusters correlated with survival. The immune suppressed cluster is associated with worse survival, enriched with myeloid-derived cells, and an epithelial-mesenchymal transition signature. The immune hot cluster is 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.
| S-EPMC10232490 | biostudies-literature
Project description:WGS data for manuscript titled: Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy
| EGAD00001008646 | EGA
Project description:RNA-Seq data for manuscript titled: Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy
| EGAD00001008656 | EGA
Project description:To use gene expression profiles to predict response to neoadjuvant chemoradiotherapy in oesophageal cancer patients.
2008-02-08 | E-MEXP-426 | biostudies-arrayexpress
Project description:Neoadjuvant chemoradiation therapy (CRT) is a widely used preoperative treatment strategy for locally advanced rectal cancer (LARC). However, a few studies have evaluated the molecular changes caused by neoadjuvant CRT in these cancer tissues. Here, we aimed to investigate changes in immunotherapy-related immunogenic effects in response to preoperative CRT in LARC. We analyzed 60 pairs of human LARC tissues before and after irradiation from three independent LARC cohorts, including a LARC patient RNA sequencing (RNA-seq) dataset from our cohort and GSE15781 and GSE94104 datasets. Gene ontology analysis showed that preoperative CRT significantly enriched the immune response in LARC tissues. Moreover, gene set enrichment analysis revealed six significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways associated with downregulated genes, including mismatch repair (MMR) genes, in LARC tissues after CRT in all three cohorts. Radiation also induced apoptosis and downregulated various MMR system-related genes in three colorectal cancer cells. One patient with LARC showed a change in microsatellite instability (MSI) status after CRT, as demonstrated by the loss of MMR protein and PCR for MSI. Moreover, CRT significantly increased tumor mutational burden in LARC tissues. CIBERSORT analysis revealed that the proportions of M2 macrophages and CD8 T cells were significantly increased after CRT in both the RNA-seq dataset and GSE94104. Notably, preoperative CRT increased various immune biomarker scores, such as the interferon-γ signature, the cytolytic activity and the immune signature. Taken together, our findings demonstrated that neoadjuvant CRT modulated the immune-related characteristics of LARC, suggesting that neoadjuvant CRT may enhance the responsiveness of LARC to immunotherapy.
2023-05-31 | GSE233517 | GEO
Project description:Integrative multi-omic approaches have been increasingly applied to discovery and functional studies of complex human diseases. Short-term preoperative antibiotics have been adopted to reduce site infections in colorectal cancer (CRC) resections. We hypothesize that the antibiotics will impact analysis of multi-omic datasets generated from resection samples to investigate biological CRC risk factors. To assess the impact of preoperative antibiotics on integrated microbiome and human transcriptomic data generated from archived frozen CRC resection samples. Genomic DNA (gDNA) and RNA were extracted from 51 pairs of frozen sporadic CRC tumor and adjacent non-tumor mucosal samples from 50 CRC patients archived at a single medical center. 16S rRNA gene sequencing (V3V4 region, paired end (PE), 300 bp) and confirmatory quantitative polymerase chain reaction (qPCR) assays were conducted on gDNA. RNA sequencing IPE, 125bp) was performed on parallel tumor and non-tumor RNA samples with RNA Integrity Numbers (RIN) scores ≥ 6.
2021-04-21 | GSE165255 | GEO
Project description:Background: Neoadjuvant radiotherapy (neo-RT) is widely used in locally advanced rectal cancer (LARC) as a component of radical treatment. Despite the advantages of neo-RT, which typically improves outcomes in LARC patients, the lack of reliable biomarkers that predict response and monitor the efficacy of therapy, can result in the application of unnecessary aggressive therapy affecting patients’ quality of life. Hence, the search for molecular biomarkers for assessing the radio responsiveness of this cancer represents a relevant issue. Methods: Here, we combined proteomic and metabolomic approaches to identify molecular signatures, which could discriminate LARC tumors with good and poor responses to neo-RT. Results: The integration of data on differentially accumulated proteins and metabolites made it possible to identify disrupted metabolic pathways and signaling processes connected with response to irradiation, including ketone bodies synthesis and degradation, purine metabolism, energy metabolism, degradation of fatty acid, amino acid metabolism, and focal adhesion. Moreover, we proposed multi-component panels of proteins and metabolites which could serve as a solid base to develop biomarkers for monitoring and predicting the efficacy of preoperative RT in rectal cancer patients. Conclusions: We proved that an integrated multi-omic approach presents a valid look at the analysis of the global response to cancer treatment from the perspective of metabolomic reprogramming.
2024-05-22 | PXD048647 | Pride
Project description:We evaluated and correlated gene expression profiles of pre-treatment endoscopic biopsies in a pre-defined patient population of resectable oesophageal adenocarcinoma who had received neoadjuvant platinum and fluoropyrimidine based chemotherapy with clinical outcome, the primary end-point being overall survival. At the time of pre-treatment staging EUS, tumour biopsies were collected (approximately 1.5 mm3). and immediately snap frozen and stored in liquid nitrogen. Total RNA was extracted from the biopsies and amplified using a T7 bacteriophage RNA polymerase based linear amplification protocol, then expression profiling was carried out. The expression levels of 47 genes selected by biological function, fold change and degree of significance were further validated using quantitative reverse transcription-PCR Keywords: Tumour vs normal comparison
2008-08-15 | GSE11595 | GEO
Project description:Differential gene expression analysis of oesophageal cells stimulated with a low pH environment. Study designed to identify pathways involved in progression of gastro-oesophageal reflux disease through Barrett's oesophagus to adenocarcinoma. Identified many subsets of genes with involvement in pathogenesis. Keywords = GORD Keywords = Barrett's Oesophagus Keywords = Oesopageal Adenocarcinoma. Keywords: time-course
2005-10-04 | GSE2144 | GEO