Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA222227 | ENA |
REPOSITORIES: ENA
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Project description:Adenomatous polyposis coli (APC) is an important tumor suppressor and most directly related to the regulation of WNT/β-catenin signaling pathway. APC mutation has been identified as an early event in more than 80% of sporadic colorectal cancers (CRCs). However, obvious prognostic differences are observed in CRC patients with APC mutations. Although previous genomics has investigated the roles of concomitant gene mutations in determining the phenotypic heterogeneity of APC-mutant tumors, valuable prognostic determinants for APC-mutant CRC patients are still lacking. By using combined proteome and phosphoproteome, we classified the APC-mutant colon cancer patients and revealed the genomic, proteomic and phosphoproteomic heterogeneity in APC-mutant tumors. Of importance, we identified RAI14 as a key prognostic determinant for APC-mutant colon cancer patients, but not for APC-wildtype colon cancer patients. The heterogeneity and prognostic biomarkers in APC-mutant tumors were further confirmed in Clinical Proteomic Tumor Analysis Consortium (CPTAC) colon cancer cohort. In addition, we found that knockdown of RAI14 in cell lines led to reduced cell migration and changes in some epithelial-mesenchymal transition (EMT)-related markers. Mechanistically, knockdown of RAI14 was able to remodel the phosphoproteome associated with cell adhesion, which might promote F-action degradation and alter the expression of certain EMT markers. Collectively, this work describes the phenotypic heterogeneity of APC-mutant tumors and identifies the prognostic determinants for APC-mutant colon cancer patients. The prognostic utility of RAI14 in APC-mutant colon cancer will provide early warning and increase the chance of successful treatment.
2022-11-10 | PXD038081 |
Project description:The tumor microenvironment strongly influences cancer development, progression and metastasis. The role of carcinoma-associated fibroblasts (CAFs) in these processes and their clinical impact has not been studied systematically in non-small cell lung carcinoma (NSCLC). We established primary cultures of CAFs and matched normal fibroblasts (NFs) from 15 resected NSCLC. We demonstrate that CAFs have greater ability than NFs to enhance the tumorigenicity of lung cancer cell lines. Microarray gene expression analysis of the 15 matched CAF and NF cell lines identified 46 differentially expressed genes, encoding for proteins that are significantly enriched for extracellular proteins regulated by the TGF-beta signaling pathway. We have identified a subset of 11 genes that formed a prognostic gene expression signature, which was validated in multiple independent NSCLC microarray datasets. Functional annotation using protein-protein interaction analyses of these and published cancer stroma-associated gene expression changes revealed prominent involvement of the focal adhesion and MAPK signalling pathways. Fourteen (30%) of the 46 genes also were differentially expressed in laser-capture micro-dissected corresponding primary tumor stroma compared to the matched normal lung. Six of these 14 genes could be induced by TGF-beta1 in NF. The results establish the prognostic impact of CAF-associated gene expression changes in NSCLC patients. This SuperSeries is composed of the following subset Series: GSE22862: Prognostic Gene Expression Signature of Carcinoma Associated Fibroblasts in Non-Small Cell Lung Cancer [expression profiling_CAFs] GSE22863: Prognostic Gene Expression Signature of Carcinoma Associated Fibroblasts in Non-Small Cell Lung Cancer [expression profiling_NSCLC stroma] GSE27284: Prognostic Gene Expression Signature of Carcinoma Associated Fibroblasts in Non-Small Cell Lung Cancer [methylation profiling] GSE27289: Prognostic Gene Expression Signature of Carcinoma Associated Fibroblasts in Non-Small Cell Lung Cancer [genome variation profiling]
2011-04-08 | E-GEOD-22874 | biostudies-arrayexpress
Project description:Single-cell RNA-sequencing analyses were performed on unfractionated live cell mixtures or sorted fibroblasts from pancreatic tumors of KPC;YFP mice, so as to investigate the functional heterogeneity of cancer-associated fibroblasts in early-stage and late-stage tumors.
2022-03-19 | GSE198815 | GEO
Project description:This is a phase 2, randomized study where the aim of the study is to investigate the tolerance of adjuvant chemotherapy, measured by functional decline, after surgery for colon cancer stage III in elderly patients. Secondary aims are disease-free survival, toxicity, late functional outcome, quality of life, to establish a geriatric assessment for selection of patients, and to examine the prognostic value of gene signature tests / biomarkers for stage III colon cancer.
| 2230974 | ecrin-mdr-crc
Project description:Cancer stem cells (CSCs) are profoundly associated with refractory nature of cancer. A quiescent population of CSCs is responsible for tumorigenesis and chemoresistance in leukemia, whereas neither the presence nor clinical importance of the quiescent CSCs is clearly established in solid tumors. In colon cancer, LGR5 is regarded as a functional marker of CSCs, but heterogeneity among LGR5+ cells was not clearly defined. Here we stratified LGR5+ cells by single-cell gene expression analyses and revealed that a tumorigenic population of mouse LGR5+ cells resides in a quiescent state. We identified 23 signature genes that were uniquely expressed in the quiescent CSCs of mouse tumors, and found that 7 of them were also specifically expressed in a quiescent population of LGR5+ cells in human colon xenograft tumors. Among them, PROX1 was expressed in invasive fronts of colon tumors. PROX1 was induced by TCF1 (TCF7), and the TCF1-mediated PROX1 expression was responsible for not only the maintenance of quiescence but also chemoresistance of colon cancer organoids. Knockout of PROX1 in patient-derived xenograft tumors resulted in inhibition of tumor recurrence after chemotherapeutic treatment. Our data underscore the therapeutic importance of a quiescent CSC population in colon cancer.
2019-11-30 | GSE141157 | GEO
Project description:Functional heterogeneity of cancer-associated fibroblasts in pancreatic cancer
| PRJNA816929 | ENA
Project description:Cancer associated fibroblasts (CAFs) are well known to strongly influence tumor development, progression, and metastasis. Their characteristics and prognostic gene signature in non-small cell lung cancer (NSCLC) patients have been recognized. Heterogeneity of CAFs has long been observed, however, the functional heterogeneity of CAFs between patients and their genetic basis are far less known. Here, we report the distinction of two CAF subtypes obtained from primary cultures of CAFs and matched normal fibroblasts (NFs) from 28 resected NSCLC. These 28 pathological NSCLC (82 % adenocarcinoma) were categorized into two types according to the histological properties of the peritumoral stroma: High desmoplasia (HD; n=14), and low desmoplasia (LD; n=14), and the prognostic significance evaluated. This classification seems to align with functional CAFs, as those with HD have higher rate of gel contraction, higher rate of tumor growth and poor prognosis. To demonstrate a gene expression profile specific to CAF activity we used Illumina DASAL Microarray gene expression analysis on extracted RNA from 24 CAF cell lines (12 CAFs-HD and 12 CAFs-LD) that were embedded in collagen gel for 24 hours. From the CAF cohort, the most significant genes that are correlated with the desmoplasia are identified to be enriched in the clinical cohort of 181 NSCLC patients. Overall, our studies showed that in NSCLC, desmoplasia is significantly associated with poor prognosis and is able to significantly subgroup CAF between NSCLC patients.
2019-04-17 | GSE116679 | GEO
Project description:Clinical heterogeneity of gastric cancer reflected in unequal outcome of treatment is poorly defined in molecular level, and molecular subtypes and their associated biomarkers have not been established to improve prognostification and treatment of gastric cancer. Using microarray technologies, we analyzed gene expression profiling data from patients with advanced gastric cancer and uncovered potential prognostic subtypes and identify gene expression signature associated with prognosis. Using microarray technologies, we analyzed gene expression profiling data from patients with advanced gastric cancer and uncovered potential prognostic subtypes and identify gene expression signature associated with prognosis.
2012-04-29 | E-GEOD-28541 | biostudies-arrayexpress
Project description:Enhancer aberrations are beginning to emerge as a key feature of colorectal cancers, however, we have limited understanding of epigenomic patterns that distinguish tumors and underlying heterogeneity between tumors. Here, using epigenomic profiling of colorectal tumors, adenomas and normal colon tissues, we identify unique pattern of regulatory elements in colorectal cancer, which could reliably distinguish tumors from normal colon specimens. We define shared and unique enhancer elements during colorectal cancer progression using normal adjacent colon, adenomas and adenocarcinomas. We validate the functional nature of tumor-specific enhancers for important oncogenes such as ASCL2 and Fzd10. NMF clustering identified 4 epigenetic (EPIC) subtypes in colorectal cancer, which mimics consensus molecular subtypes (CMS)1, with an advantage of introducing a novel epigenetically-identifiable subtype with poor prognosis and survival. Based on this correlation, we defined and validated a combination therapeutic strategy of enhancer-blocking BETi with pathway specific inhibitor for 3 CMS subtypes. In conclusion, by comprehensive characterization of chromatin state patterns in colorectal tumors, we define epigenomic patterns during tumor evolution, heterogeneity of enhancers among patients and a combination therapy strategy for CMS-subgroups.
2021-05-22 | GSE136630 | GEO
Project description:Enhancer aberrations are beginning to emerge as a key feature of colorectal cancers, however, we have limited understanding of epigenomic patterns that distinguish tumors and underlying heterogeneity between tumors. Here, using epigenomic profiling of colorectal tumors, adenomas and normal colon tissues, we identify unique pattern of regulatory elements in colorectal cancer, which could reliably distinguish tumors from normal colon specimens. We define shared and unique enhancer elements during colorectal cancer progression using normal adjacent colon, adenomas and adenocarcinomas. We validate the functional nature of tumor-specific enhancers for important oncogenes such as ASCL2 and Fzd10. NMF clustering identified 4 epigenetic (EPIC) subtypes in colorectal cancer, which mimics consensus molecular subtypes (CMS)1, with an advantage of introducing a novel epigenetically-identifiable subtype with poor prognosis and survival. Based on this correlation, we defined and validated a combination therapeutic strategy of enhancer-blocking BETi with pathway specific inhibitor for 3 CMS subtypes. In conclusion, by comprehensive characterization of chromatin state patterns in colorectal tumors, we define epigenomic patterns during tumor evolution, heterogeneity of enhancers among patients and a combination therapy strategy for CMS-subgroups.
2021-05-22 | GSE136629 | GEO