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.
Project description:The investigators hypothesize that abnormalities in thromboelastography (TEG) parameters in patients with liver, pancreas, biliary, esophageal, colorectal, and lung adenocarcinoma can serve as biomarkers for oncologic disease burden, cancer recurrence and overall survival as well as thrombotic and hemorrhagic post-operative complications. The investigators further hypothesize that there is histologic pathology correlates to pre-operative TEG abnormalities, and that it identifies patients with virulent tumor biology.
Project description:Pancreatic cancer is the 3rd most prevalent cause of cancer related deaths in United states alone, with over 55000 patients being diagnosed in 2019 alone and nearly as many succumbing to it. Late detection, lack of effective therapy and poor understanding of pancreatic cancer systemically contributes to its poor survival statistics. Obesity and high caloric intake linked co-morbidities like type 2 diabetes (T2D) have been attributed as being risk factors for a number of cancers including pancreatic cancer. Studies on gut microbiome has shown that lifestyle factors as well as diet has a huge effect on the microbial flora of the gut. Further, modulation of gut microbiome has been seen to contribute to effects of intensive insulin therapy in mice on high fat diet. In another study, abnormal gut microbiota was reported to contribute to development of diabetes in Db/Db mice. Recent studies indicate that microbiome and microbial dysbiosis plays a role in not only the onset of disease but also in its outcome. In colorectal cancer, Fusobacterium has been reported to promote therapy resistance. Certain intra-tumoral bacteria have also been shown to elicit chemo-resistance by metabolizing anti-cancerous agents. In pancreatic cancer, studies on altered gut microbiome have been relatively recent. Microbial dysbiosis has been observed to be associated with pancreatic tumor progression. Modulation of microbiome has been shown to affect response to anti-PD1 therapy in this disease as well. However, most of the studies in pancreatic cancer and microbiome have remained focused om immune modulation. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to Gemcitabine/Paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group.
Project description:Esophageal cancer, a highly lethal tumor, contributes to 5% of all cancer deaths, with its primary subtypes being esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). While most studies focus on ESCC, this study investigates EAC using single-cell RNA sequencing (scRNA-seq) to analyze CD45+ immune cells from tumors and matched non-tumor tissues in therapy-naïve patients. By examining the transcriptional profiles of these immune cells and the entire transcriptome in a cohort of 23 patients, the study identifies distinct transcriptional signatures. These signatures were used to stratify a large cohort of TCGA EAC patients, revealing strong associations with prognosis and clinical outcomes. The findings suggest that these transcriptional profiles can improve prognosis accuracy post-surgery and potentially guide effective therapies, including immunotherapy, for EAC patients.
Project description:Esophageal cancer, a highly lethal tumor, contributes to 5% of all cancer deaths, with its primary subtypes being esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). While most studies focus on ESCC, this study investigates EAC using single-cell RNA sequencing (scRNA-seq) to analyze CD45+ immune cells from tumors and matched non-tumor tissues in therapy-naïve patients. By examining the transcriptional profiles of these immune cells and the entire transcriptome in a cohort of 23 patients, the study identifies distinct transcriptional signatures. These signatures were used to stratify a large cohort of TCGA EAC patients, revealing strong associations with prognosis and clinical outcomes. The findings suggest that these transcriptional profiles can improve prognosis accuracy post-surgery and potentially guide effective therapies, including immunotherapy, for EAC patients.
Project description:We have investigated expressed microRNA in cryo-preserved esophageal cancer tissues using advanced microRNA microarray techniques. Our microarray analyses reveal a unique microRNA expression signature composed of 40 genes which can distinguish normal from malignant esophageal tissue. Some microRNAs could be correlated with the different clinico-pathological classifications. For example, high hsa-miR-103, -107, -23b expression correlated with poor overall disease-free survival of esophageal cancer patients. These results indicate that microRNA expression profiles are important diagnostic and prognostic markers of esophageal cancer, which might be analyzed simply using economical approaches such as RT-PCR. Keywords: microRNA, esophageal squamous cell carcinoma
Project description:This SuperSeries is composed of the following subset Series: GSE32700: Overall aiEMT in non-cancerous samples of esophageal cancer patients GSE32701: Individual aiEMT in surgical samples of esophageal cancer patients Refer to individual Series
Project description:Rates of esophageal adenocarcinoma are rising globally, with risk factors including a range of genetic and environmental factors, including obesity, tobacco smoking, TP53 mutations, and Barrett’s esophagus, a proinflammatory condition which often occurs prior to developing adenocarcinoma. Interestingly, these factors also modulate the gastrointestinal microbiome. To better understand the linkage between the microbiome, inflammation, and development of esophageal adenocarcinoma, we integrated 16S and RNA sequencing data. We found several microbial taxa enriched in tumor samples which were correlated with predicted immune cell infiltration from RNA-seq data, including a decrease in megakaryocyte-erythroid progenitor cells with a concomitant increase in platelets. These data suggest dysbiosis of the intratumoral microbiome promotes development and production of platelets, which reveal alterations in the immune microenvironment of esophageal adenocarcinoma and suggest novel therapeutic targets.
2024-02-07 | GSE234304 | GEO
Project description:Oral and Esophageal Microbiota in Patients with Esophageal Cancer