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Estrogen related receptor alpha drives mitochondrial biogenesis and resistance to neoadjuvant chemoradiation in esophageal cancer

ABSTRACT: Following exposure to chemoradiation, EAC cells increase their mitochondrial content and associated metabolic processes, which drives treatment resistance. Inhibition of this response using clinically applicable inhibitors of ESRRA in combination with (chemo)radiation shows promising anti-tumor activities and could be further developed for clinical use.

ORGANISM(S): Homo sapiens

PROVIDER: GSE184654 | GEO | 2022/10/17

REPOSITORIES: GEO

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Peripheral circulating mRNA profiling in predicting the pathological response to neoadjuvant chemoradiation for esophageal squamous cell carcinoma

Project description:Analysis of peripheral circulating mRNA expression levels in patients undergoing neoadjuvant chemoradiation for esophageal squamous cell carcinoma. The hypothesis test was that chemoradiation alters the circulating mRNA expression profiles and the profiling is predictive of pathological response. Results provide information on the response of circulating mRNAs to chemoradiation and identify novel biomarkers or targets in esophageal squamous cell carcinoma. Total RNA obtained from peripheral whole blood before and after neoadjuvant chemoradiation in patients with esophageal squamous cell carcinoma. 21 patients with 42 samples were analyzed. The expression profiles from pathological complete responders were compared to non-complete responders.

2014-01-01 | E-GEOD-43519 | biostudies-arrayexpress

Peripheral circulating mRNA profiling in predicting the pathological response to neoadjuvant chemoradiation for esophageal squamous cell carcinoma

2014-01-01 | GSE43519 | GEO

Identification of novel molecular subgroups in esophageal adenocarcinoma to predict response to neo-adjuvant therapies

Project description:Esophageal adenocarcinoma (EAC) is a highly aggressive cancer and its response to chemo-, and radiotherapy is unpredictable. EAC are highly heterogeneous at the molecular level. The aim of this study was to perform gene expression analysis of EAC to identify distinct molecular subgroups and to investigate expression signatures in relation to treatment response.

2023-01-08 | GSE207526 | GEO

The pluripotency factor NANOG contributes to mesenchymal plasticity and is predictive for outcome in esophageal adenocarcinoma

Project description:Despite the advent of neoadjuvant chemoradiotherapy (CRT), overall survival rates of esophagealadenocarcinoma(EAC) remain low. A readily induced mesenchymal transition of EAC cells contributes to resistance to CRT. In this study, we aimed to chart the heterogeneity in cell state transition after CRT and to identify its underpinnings. RNA-sequencing was performed on 100 pre-treatment biopsies. After RNA-sequencing, Ridge regression analysis was applied to correlate gene expression to ranked plasticity, and models were developed to predict mesenchymal transitions in patients. Plasticity score predictions of the three highest significant predictive models were projected on the pre-treatment biopsies and related to clinical outcome data. A motif enrichment analysis of the genes associated with all three models revealed NANOG as the key associated transcription factor. In accordance, expression of NANOG in pre-treatment biopsies was highly associated with poor response to neoadjuvant chemoradiation, the occurrence of recurrences, and median overall survival difference in EAC patients (>48 months).

2024-05-15 | GSE254942 | GEO

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.

2023-02-28 | GSE222078 | GEO

Proteomic Analysis to Identify Markers for Response to Neoadjuvant Treatment in Esophageal and Gastroesophageal Cancer

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.

2022-05-20 | PXD025192 | Pride

Transcription profiling of untreated and cisplatin-based chemoradiation treated human squamous cell carcinomas to improve prediction of outcome after chemoradiation

Project description:Gene expression profiling to predict outcome after chemoradiation in head and neck cancer Purpose. The goal of the present study was to improve prediction of outcome after chemoradiation in advanced head and neck cancer using gene expression analysis. Materials and Methods. We collected 92 biopsies from untreated head and neck cancer patients subsequently given cisplatin-based chemoradiation (RADPLAT) for advanced squamous cell carcinomas (HNSCC). After RNA extraction and labeling we performed dye swap experiments using 35k oligo-microarrays. Supervised analyses were performed to create classifiers to predict local control, locoregional control and disease recurrence. Published gene sets with prognostic value in other studies were also tested. Results. Using supervised classification on the whole series, gene sets separating good and poor outcome could be found for all end-points. However, when splitting tumors into training and validation groups, no robust classifiers could be found. Also previously published signatures with prognostic value have been tested. Conclusion. Gene sets can be found with predictive potential for locoregional control after combined radiation and chemotherapy in HNSCC. How treatment-specific these gene sets are needs further study.

2008-02-19 | E-NCMF-8 | biostudies-arrayexpress

Non responders to neoadjuvant chemoradiation for esophageal cancer: why better prediction is necessary.

Project description: Not available

| S-EPMC5538978 | biostudies-other

Proteome profiles of primary pancreatic ductal adenocarcinomas undergoing adjuvant chemoradiation link ALDH1A1 to early local recurrence and chemoradiation resistance

Project description:Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis with very frequent post-surgical local recurrence. The combination of adjuvant chemotherapy with radiotherapy is under consideration to achieve a prolonged disease-free survival (DFS). To date, few studies have determined protein profiles that are associated with responsiveness to adjuvant chemoradiation. Here, we analyzed the proteomes of primary, surgically resected PDAC tumors subjected to adjuvant chemoradiation and achieving short DFS (median DFS of 6 months, n = 6) or a prolonged DFS (median DFS of 28 months, n = 6) using liquid chromatography tandem mass spectrometry.

2018-09-11 | PXD009254 | Pride

Neoadjuvant chemoradiation alters biomarkers of anticancer immunotherapy responses in locally advanced rectal cancer

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

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