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The single cell transcriptional landscape of esophageal adenocarcinoma and its modulation by neoadjuvant chemotherapy

ABSTRACT: The single cell transcriptional landscape of esophageal adenocarcinoma and its modulation by neoadjuvant chemotherapy

PROVIDER: PRJNA917632 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22957200.fastq.gz	Fastqsanger.gz
	SRR22957201.fastq.gz	Fastqsanger.gz
	SRR22957202.fastq.gz	Fastqsanger.gz
	SRR22957203.fastq.gz	Fastqsanger.gz
	SRR22957204.fastq.gz	Fastqsanger.gz

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The single cell transcriptional landscape of esophageal adenocarcinoma and its modulation by neoadjuvant chemotherapy

Project description:Immune checkpoint blockade has recently proven effective in a subset of patients with esophageal adenocarcinoma (EAC) but little is known regarding the EAC immune microenvironment. We determined the single cell transcriptional profile of EAC in patients who were treatment naive or had received neoadjuvant chemotherapy. Analysis of 52,387 cells revealed 10 major cell subsets of tumor, immune and stromal cells. Prior to chemotherapy tumors were characterised by infiltration with effector T cells showing markers of exhaustion together with large T regulatory cell infiltrates. Plasmacytoid dendritic cells were markedly expanded whilst two dominant cancer-associated fibroblast populations were observed. Pathological remission following chemotherapy was associated with broad reversal of immune abnormalities together with an increase in endothelial and myofibroblast populations although a chemoresistant epithelial stem cell population was apparent. These findings reveal features that underlie and limit the response to current immunotherapy and reveal a range of novel opportunities for targeted therapy.

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Project description:Background and Purpose: The current standard of care for locally advanced esophageal and gastroesophageal junctional cancer is neoadjuvant chemoradiation (NCRT) followed by surgery. The genomic and proteomic pathways responsible for response to neoadjuvant chemoradiation are sparsely described, and thus response to treatment cannot be reliably predicted. In this study, we performed an in-depth proteomic analysis of esophageal and gastroesophageal tumors, to describe differences in pathway activation between patients with good and poor prognosis following neoadjuvant chemoradiation. Materials and Methods: This study included locally advanced esophageal and gastroesophageal cancer patients treated with NCRT. The study cohort was dichotomized into two groups of patients- good prognosis (GP) and bad prognosis (BP) according to the post-operative disease-free interval. We performed a mass spectrometry analysis of proteins extracted from the malignant regions of surgical specimens and analyzed data from electronic medical records. Clinical data was correlated with differences in protein expression between GP and BP using validated gene expression pathways. Results: The study included thirty-five patients with adenocarcinoma. GP and BP had statistically significant differences in protein expression patterns. GP exhibited differential enrichment of pathways related to cellular respiration, oxidative phosphorylation and proteins of the RAS oncogene family. Conclusion: In this study we identify enrichment of pathways related to oxidative phosphorylation and RAS oncogene pathway in esophageal cancer patients with a favorable response to NCRT. Larger transcriptomic studies are warranted to portray potential surrogate signature of biomarkers based upon these potential pathways.

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Barrett's esophageal tissues and esophageal adenocarcinoma specimens

Project description:This SuperSeries is composed of the following subset Series: GSE37200: Gene expression profiling of Barrett’s esophageal tissues and esophageal adenocarcinoma specimens GSE37201: Gene expression profiling of esophageal adenocarcinoma Refer to individual Series

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