Project description:Identifying biomarkers predictive for early esophageal cancer detection is critical considering the dismal survival rates. We investigated the involvement of microRNAs (miRNAs), their utility as biomarkers, and their association with survival in esophageal cancer, including Barrett’s associated and sporadic adenocarcinoma (ADC), and squamous cell carcinoma (SCC). MiRNA expression was measured in cancerous and adjacent non-cancerous tissue pairs collected from 76 US and Japanese patients enrolled in 3 distinct cohorts. In ADC patients, miR-21, miR-194, miR-293, and miR-223 expression was elevated, while miR-375 and miR-203 expression was reduced in cancerous tissue compared to non-cancerous tissue. Increased levels of miR-192 and miR-194 were observed in Barrett’s associated compared to sporadic ADC cancerous tissue. In SCC patients, miR-21, miR-181b, miR-155, and miR-146b expression was elevated while miR-375 and miR-203 levels were reduced in cancerous tissue compared to non-cancerous tissue. Significantly, elevated mir-21 expression in non-cancerous tissue was strongly associated with worse prognosis, independent of nodal status and age. Sample classification using miRNA expression yielded accuracies as high as 86% for diagnosis and 78% for Barrett’s esophagus status. Our results highlight that miRNAs are deregulated in esophageal carcinogenesis and Barrett’s esophagus, and that their expression is associated with survival in cancer patients. Sample classification using miRNA expression demonstrates their potential utility as biomarkers for esophageal carcinoma diagnosis. MiRNA microarray expression was measured using miRNA microarray chips version 3 (Ohio State University) in 44 SCC cases and 32 ADC cases, of which 18 were also diagnosed with Barrett’s esophagus.
Project description:Identifying biomarkers predictive for early esophageal cancer detection is critical considering the dismal survival rates. We investigated the involvement of microRNAs (miRNAs), their utility as biomarkers, and their association with survival in esophageal cancer, including Barrett’s associated and sporadic adenocarcinoma (ADC), and squamous cell carcinoma (SCC). MiRNA expression was measured in cancerous and adjacent non-cancerous tissue pairs collected from 76 US and Japanese patients enrolled in 3 distinct cohorts. In ADC patients, miR-21, miR-194, miR-293, and miR-223 expression was elevated, while miR-375 and miR-203 expression was reduced in cancerous tissue compared to non-cancerous tissue. Increased levels of miR-192 and miR-194 were observed in Barrett’s associated compared to sporadic ADC cancerous tissue. In SCC patients, miR-21, miR-181b, miR-155, and miR-146b expression was elevated while miR-375 and miR-203 levels were reduced in cancerous tissue compared to non-cancerous tissue. Significantly, elevated mir-21 expression in non-cancerous tissue was strongly associated with worse prognosis, independent of nodal status and age. Sample classification using miRNA expression yielded accuracies as high as 86% for diagnosis and 78% for Barrett’s esophagus status. Our results highlight that miRNAs are deregulated in esophageal carcinogenesis and Barrett’s esophagus, and that their expression is associated with survival in cancer patients. Sample classification using miRNA expression demonstrates their potential utility as biomarkers for esophageal carcinoma diagnosis.
Project description:The aim of this study is to generate and validate biomarkers to stratify patients with Barrett’s esophagus in terms of risk for developing cancer. We studied gene expression profiling in 69 frozen specimens, consisting of esophageal squamous epithelium from 19 healthy subjects, 20 specimens from patients with Barrett’s esophagus and 21 cases of esophageal adenocarcinoma, 9 cased of esophageal squamous cell carcinoma by whole genome microarray analysis. Laser capture microdissection technique was applied to procure cells from defined regions of Barrett’s esophagus metaplasia and esophageal adenocarcinoma. Microarray results were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in an independent cohort consisting of 42 cases. Furthermore, immunohistochemistry was performed using antibodies to two selected target molecules on a third independent cohort of 36 specimens, consisting of 36 cases. A total of 1176 genes were associated significantly with esophageal adenocarcinoma. The expression pattern of a 4 gene signature with the highest discriminant score based on linear discriminant analysis (GeneSpring GX10.2), was identified and validated by qRT-PCR in independent cohort. Gene expression profiling of 20 specimens of Barrett's esophagus patients, 21 specimens of adenocarcinoma patients and 19 biopsies from patients with normal esophageal squamous epithelium, 9 specimens of squamous cell carcinoma were studied.
Project description:The human miRNA profiles of esophageal squamous cell carcinoma are rarely reported. Surgically removed human ESCC tissues and matched normal esophageal epithelial tissues (5cm away from tumor) were collected to make an Agilent microarray. Three paired of human ESCC tissues and normal controls were collected. All patients have no radiotherapy or chemotherapy before surgery. None of these three patients have distant metastasis.
Project description:Esophageal squamous cell carcinoma (SCC) is frequently diagnosed at advanced stage and associated with poor prognosis. This study aimed to identify differentially expressed genes for further evaluated as biomarkers for predicting survival of the patients. Five paired of cancerous and normal tissues from esophageal SCC patients were subjected to cDNA microarray analysis and one of these differentially expressed genes, NEK6, was further verified in esophageal SCC tissues. The data showed 444 up-regulated genes and 918 down-regulated genes in tumor tissues (2 folds as a cut-off value). qRT-PCR data showed that 20 of 30 (66.7%) increased levels of NEK6 mRNA in cancerous tissues compared to that of distant normal tissues, while immunohistochemical data showed that 49/94 (52.13%) of the archived esophageal SCC tissues expressed higher levels of NEK6 than that of normal tissues. NEK6 expression was associated with depth of tumor invasion (P=0.005), lymph node metastasis (P=0.018), and advanced clinical tumor stages (P=0.004) of these 94 patients. Kaplan Meier curve showed that the overall survival of NEK6-positive patients was much lower than those of NEK6-negative patients (P<0.001). The median survival of NEK6-positive patients was 23 months, whereas the median survival of NEK6-negative patients was 64 months. The cumulative 5-year survival rate of NEK6-positive patients was 14.3% (7/49), whereas the rate of NEK6-negative patients was 64.4% (29/45). Multivariate analysis showed that N classification (P=0.002) and NEK6 expression (P<0.001) were independent predictors for esophageal SCC patients. These data demonstrated that NEK6 expression may serve as an independent prognostic indicator for patients with esophageal SCC. Gene expression in five paired of cancerous and normal tissues from esophageal SCC patients were measured using Human Genome 4x44K v2 Microarray.
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.
Project description:To understand the difference of protein expression between paired esophageal squamous cell carcinoma (ESCC) and adjacent normal tissues, we collected 10 paired ESCC and normal tissues from surgical resected specimems for high-throughput proteomic experiments. From comparative analysis, the dysregulated signaling pathways in ESCC could be uncovered.
Project description:The Lung3 data set consists of 89 NSCLC patients that were treated at MAASTRO Clinic, The Netherlands. For these patients pretreatment CT scans, tumour delineations and gene expression profiles were available. We used this data set to associate imaging features with gene-expression profiles. 89 samples from NSCLC patients. Samples were obtained by biopsies from cancerous tissue. Tumors were classified as Adenocarcinoma, Papillary, NOS; Squamous Cell Carcinoma, NOS; Non-Small Cell; Papillary Type; or Solid Type.
Project description:To screen microRNAs (miRNAs) that are deregulated in head and neck squamous cell carcinoma (HNSCC), we comparatively analyzed the miRNA profiles by using 10 HNSCC patient samples and paired adjacent non-cancerous counterparts. Microarray analysis revealed that 24 miRNAs were downregulated and 19 miRNAs were elevated in HNSCC samples when compared with adjacent non-cancerous tissue. These miRNAs included upregulated miR-21-5p, miR-21-3p, and downregulated miR-99a-5p, which have been reported to regulate malignant progression of HNSCC in previous studies.
Project description:Esophageal adenocarcinoma arises from Barrett’s esophagus, a precancerous metaplastic replacement of squamous by columnar epithelium in response to chronic inflammation. Multi-omics profiling, integrating single-cell transcriptomics, extracellular matrix proteomics, tissue-mechanics and spatial proteomics of 64 samples from 12 patients’ paths of progression from squamous epithelium through metaplasia, dysplasia to adenocarcinoma, revealed shared and patient-specific progression characteristics. The classic metaplastic replacement of epithelial cells was paralleled by metaplastic changes in stromal cells, ECM and tissue stiffness. Strikingly, this change in tissue state at metaplasia was already accompanied by appearance of fibroblasts with characteristics of carcinoma-associated fibroblasts and of an NK cell-associated immunosuppressive microenvironment. Thus, Barrett’s esophagus progresses as a coordinated multi-component system, supporting treatment paradigms that go beyond targeting cancerous cells to incorporating stromal reprogramming.