The transcriptome of nonpolypoid and polypoid preinvasive lesions of the human large intestine
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Giancarlo Marra
PROVIDER: E-GEOD-21962 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The aim was to analyze the transcriptome of different types of preneoplastic colorectal lesions in comparison with that of the corresponding normal mucosa.
2010-05-27 | GSE21962 | GEO
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Project description:Background: Colorectal cancers are believed to arise predominantly from adenomas. Although these precancerous lesions have been subjected to extensive clinical, pathological, and molecular analyses, little is currently known about the global gene expression changes accompanying their formation. Results: To characterize the molecular processes underlying the transformation of normal colonic epithelium, we compared the transcriptomes of 32 prospectively collected adenomas with those of normal mucosa from the same individuals. Important differences emerged not only between the expression profiles of normal and adenomatous tissues, but also between those of small and large adenomas. A key feature of the transformation process was the remodeling of the Wnt pathway reflected in patent over- and underexpression of 78 known components of this signaling cascade. Conclusions: Our transcriptomic profiles of normal colonic mucosa and colorectal adenomas shed new light on the early stages of colorectal tumorigenesis. Experiment Overall Design: Pedunculated, sporadic colorectal polyps and corresponding normal mucosa were obtained during colonoscopies. The tissues were collected prospectively with informed patient consent and the approval of the local Human Research Ethics Committee.
2008-06-16 | E-GEOD-8671 | biostudies-arrayexpress
Project description:Approximately two decades ago, Vogelstein and Fearon proposed the adenoma-carcinoma sequence of sporadic CRC development and illustrated the accumulation of genetic alterations during the stepwise progression, thereby providing a guideline for clinical practice. Although the detection and excision of precancerous lesions could prevent colorectal cancer and reduce mortality, 6% of adenomas will ultimately develop into colorectal cancer. Thus, this genetic model for colorectal tumorigenesis may not completely reflect the complex essence of the disease and whether the mode of initiation of the events in the multistep progression affects the outcome of CRC is still unknown. In this study, mRNA and miRNA expression profiling was performed with human colorectal tissues, including normal mucosa, adenoma and adenocarcinoma. Then, an integrated approach was adopted to establish the regulatory interaction networks that were correlated with colorectal carcinogenesis. Finally, a 55-gene signature whose expression was down-regulated in precancerous lesions compared to normal tissue was identified as a potential early indicator of CRC survival. The results suggested that genes related to immunity and homeostasis played a critical role in protection against adenoma initiation and that the altered molecular events that influence colorectal cancer prognosis may be set in an early, precancerous stage. Four types of human colorectal tissues were selected by colonoscopic resection or colorectal surgery, including 12 normal mucosae, 21 low-grade adenomas (mild or moderate atypical hyperplasia), 30 high-grade adenomas (severe atypical hyperplasia or carcinoma in situ) and 25 adenocarcinomas. Gene expression profiling analysis of these samples was performed using Agilent 4x44K human whole genome gene expression microarray (G4112F).
2015-10-16 | E-GEOD-41657 | biostudies-arrayexpress
Project description:Approximately two decades ago, Vogelstein and Fearon proposed the adenoma-carcinoma sequence of sporadic CRC development and illustrated the accumulation of genetic alterations during the stepwise progression, thereby providing a guideline for clinical practice. Although the detection and excision of precancerous lesions could prevent colorectal cancer and reduce mortality, 6% of adenomas will ultimately develop into colorectal cancer. Thus, this genetic model for colorectal tumorigenesis may not completely reflect the complex essence of the disease and whether the mode of initiation of the events in the multistep progression affects the outcome of CRC is still unknown. In this study, mRNA and miRNA expression profiling was performed with human colorectal tissues, including normal mucosa, adenoma and adenocarcinoma. Then, an integrated approach was adopted to establish the regulatory interaction networks that were correlated with colorectal carcinogenesis. Finally, a 55-gene signature whose expression was down-regulated in precancerous lesions compared to normal tissue was identified as a potential early indicator of CRC survival. The results suggested that genes related to immunity and homeostasis played a critical role in protection against adenoma initiation and that the altered molecular events that influence colorectal cancer prognosis may be set in an early, precancerous stage. Four types of human colorectal tissues were selected by colonoscopic resection or colorectal surgery, including 15 normal mucosae, 39 low-grade adenomas (mild or moderate atypical hyperplasia), 20 high-grade adenomas (severe atypical hyperplasia or carcinoma in situ) and 33 adenocarcinomas. MicroRNA expression profiling analysis of these samples was performed on Agilent 8Ã16K Human miRNA Microarray V3 (G4470C).
2015-10-16 | E-GEOD-41655 | biostudies-arrayexpress
Project description:Approximately two decades ago, Vogelstein and Fearon proposed the adenoma-carcinoma sequence of sporadic CRC development and illustrated the accumulation of genetic alterations during the stepwise progression, thereby providing a guideline for clinical practice. Although the detection and excision of precancerous lesions could prevent colorectal cancer and reduce mortality, 6% of adenomas will ultimately develop into colorectal cancer. Thus, this genetic model for colorectal tumorigenesis may not completely reflect the complex essence of the disease and whether the mode of initiation of the events in the multistep progression affects the outcome of CRC is still unknown. In this study, mRNA and miRNA expression profiling was performed with human colorectal tissues, including normal mucosa, adenoma and adenocarcinoma. Then, an integrated approach was adopted to establish the regulatory interaction networks that were correlated with colorectal carcinogenesis. Finally, a 55-gene signature whose expression was down-regulated in precancerous lesions compared to normal tissue was identified as a potential early indicator of CRC survival. The results suggested that genes related to immunity and homeostasis played a critical role in protection against adenoma initiation and that the altered molecular events that influence colorectal cancer prognosis may be set in an early, precancerous stage.
2015-10-16 | GSE41657 | GEO
Project description:Approximately two decades ago, Vogelstein and Fearon proposed the adenoma-carcinoma sequence of sporadic CRC development and illustrated the accumulation of genetic alterations during the stepwise progression, thereby providing a guideline for clinical practice. Although the detection and excision of precancerous lesions could prevent colorectal cancer and reduce mortality, 6% of adenomas will ultimately develop into colorectal cancer. Thus, this genetic model for colorectal tumorigenesis may not completely reflect the complex essence of the disease and whether the mode of initiation of the events in the multistep progression affects the outcome of CRC is still unknown. In this study, mRNA and miRNA expression profiling was performed with human colorectal tissues, including normal mucosa, adenoma and adenocarcinoma. Then, an integrated approach was adopted to establish the regulatory interaction networks that were correlated with colorectal carcinogenesis. Finally, a 55-gene signature whose expression was down-regulated in precancerous lesions compared to normal tissue was identified as a potential early indicator of CRC survival. The results suggested that genes related to immunity and homeostasis played a critical role in protection against adenoma initiation and that the altered molecular events that influence colorectal cancer prognosis may be set in an early, precancerous stage.
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Project description:Oral squamous cell carcinomas are neoplasms that are mostly preceded by precancerous lesions such as leukoplakia and erythroplakia. It is important for the clinician to know about the predilection and possibility of these precancerous conditions transforming to cancer. This will inturn help to efficiently treat and manage patients. It is therefore important to understand the molecular events that explain the biology of predilection and transformation of precancerous lesions such as erythroplakia and leukoplakia to cancer. Our study aims to identify potential biomarker proteins in precancerous lesions of leukoplakia and erythroplakia that can flag its transformation to oral cancer. Four biological replicate clinical phenotypes of healthy control, leukoplakia, erythroplakia, and oral carcinoma were recruited based on clinical screening and histopathological evaluation of buccal mucosa tissue. Differentially expressed proteins were delineated using Label-free quantitative proteomics experiment done on Orbitrap fusion Tribrid mass spectrometer in three technical replicate sets of samples. Raw files were processed using Maxquant version 2.0.1.0. and down stream analysis was done by Perseus version 1.6.15.0. Validation included functional annotation based on biological process and KEGG pathways using ClueGO plug-in of cytoscape. Hierarchical clustering, and principal component analysis were performed using ClustVis tool. Across control, leukoplakia, and cancer, l- lactate dehydrogenase A chain, plectin, and WD repeat-containing protein 1 were upregulated, whereas thioredoxin 1 and spectrin alpha chain non-erythrocytic 1 were downregulated. Across control, erythroplakia, and cancer, l- lactate dehydrogenase A chain was upregulated whereas aldehyde dehydrogenase 2, peroxiredoxin 1, Heat shock 70 kDa protein 1B, and spectrin alpha chain non-erythrocytic 1 were downregulated. We found proteins involved in leukoplakia were associated with alteration in cytoskeletal reorganization and glycolysis, while in erythroplakia they were associated with alteration in response to oxidative stress and glycolysis across phenotypes. Hierarchical clustering sub-grouped half of precancerous samples under the main branch of control and the remaining half under carcinoma. Similarly, principal component analysis identified segregated clusters of control, precancerous lesions, and cancer but erythroplakia phenotypes particularly overlapped more with cancer cluster. Label-free proteomics offers a good platform for identification of protein biomarkers that can flag premalignant conditions that could become malignant. Qualitative and quantitative protein signatures across control, precancer and cancer phenotypes explain the possible functional outcomes that dictate malignant transformation to oral carcinoma. The observations place the previously observed clinical findings of erythroplakia having more predilection for cancer, in the right perspective.
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