Prognostic epigenetic 12-genes signature in human metastatic colorectal carcinomas
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PROVIDER: PRJNA625692 | ENA |
REPOSITORIES: ENA
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Project description:Epigenetic remodeling is responsible for tumor progression and drug resistance in human colorectal carcinoma (CRC). This study addressed the hypothesis that DNA methylation profiling may identify metastatic CRC (mCRC) subtypes with defined clinical characters. Global differential methylation profile was comparatively analyzed between 24 first-line primary-resistant and 12 drug-sensitive mCRCs, two subgroups with significantly different outcome. Gene expression and methylation data from the TCGA mCRCs cohort were used to identify, among differentially methylated genes, a prognostic signature of functionally methylated genes. Twelve functionally methylated genes yielded a hierarchical clustering of patients in two well-defined subgroups with hypermethylated tumors characterized by a significantly worst relapse-free and overall survival compared to hypomethylated cancers. Interestingly, the poor prognosis cluster was enriched of CIMP-high and MSI-like cases. Furthermore, methylation events were enriched in genes located on arms q of chromosomes 13 and 20, this suggesting that epigenetic remodeling may involve selective genomic regions. Finally, the expression of the 12-genes signature and MSI-enriching genes was confirmed in two independent oxaliplatin- and irinotecan-resistant CRC cell lines. These data provide the proof of concept that the hypermethylation of specific sets of genes may provide prognostic informations being able to identify a subgroup of mCRCs with poor prognosis
2021-04-15 | GSE148766 | GEO
Project description:[original title] Metastatic Canine Mammary Carcinomas can be Identified by a Gene Expression Profile that partly Overlaps with Human Breast Cancer Profiles. Introduction: Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Methods: Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Results: Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Conclusions: Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a translational model for human breast tumors in order to identify prognostic molecular signatures and potential therapeutic targets.
2010-12-01 | GSE20718 | GEO
Project description:[original title] Metastatic Canine Mammary Carcinomas can be Identified by a Gene Expression Profile that partly Overlaps with Human Breast Cancer Profiles. Introduction: Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Methods: Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Results: Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Conclusions: Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a translational model for human breast tumors in order to identify prognostic molecular signatures and potential therapeutic targets. Thirteen simple mammary carcinomas with invasive growth and lymph node metastases at the time of tumor resection and 14 simple carcinomas without lymph node metastases were included in the study. None of the patients had radiographically detectable pulmonary metastases at the time of tumor resection. Distant metastases as the cause of death were determined postoperatively by radiographic detection of metastases or necropsy. Selection criteria for carcinomas without lymph node metastases included an invasive growth, a negative lymph node status, a histological grade III and a minimal tumor diameter above the average of the lymph node positive tumors (> 2.42 cm). All animals with non-metastatic carcinomas had a survival rate of over 24 months except animal no. 22 (2627) which developed radiographic detectable lung metastases 8 months after surgery. Tumor and lymph node histologies were evaluated independently by two board-certified pathologists, following the criteria of the WHO classification of canine mammary tumors and the Nottingham grading system. All 27 tumors were simple carcinomas and characterized by an invasive, mostly solid growth pattern, marked cellular pleomorphism, anisokaryosis and 3 or more mitotic figures per high power field.
2010-12-01 | E-GEOD-20718 | biostudies-arrayexpress
Project description:Prognostic Molecular Biomarkers for Metastatic Progression in Stage I and II Clear Cell Renal Cell Carcinomas
| PRJNA648973 | ENA
Project description:Prognostic Molecular Signatures and Biomarkers for Metastatic Progression in Stage I and II Clear Cell Renal Cell Carcinomas
| PRJNA648969 | ENA
Project description:The aim of this study is to identify prognostic gene expression signatures associated with two molecularly distinct subtypes of colorectal cancer. Samples were taken from colorectal cancers in surgically resected specimens in 96 colorectal cancer patients. The expression profiles were determined using Affymetrix Human Genome U133Plus 2.0 arrays. This is a test set for validation of prognostic gene expression signature that was developed from GSE14333. All data were normalized by using the RMA method (affy package in R/Bioconductor).
2011-06-20 | GSE29971 | GEO
Project description:Prognosis of metastatic BRAF V600E mutant colorectal cancer (CRC) is poor, and the prognostic implications of immune contextures in the tumor microenvironment (TME) for CRC remain elusive. Complement activation in the TME was significantly associated with poor OS and was correlated with TAM M2 in patients with de novo metastatic BRAF V600E mutant CRC.
2022-11-08 | GSE211576 | GEO
Project description:Prognostic Molecular Signatures for Metastatic Potential in Clinically Low-Risk Stage I and II Clear Cell Renal Cell Carcinomas
| PRJNA601152 | ENA
Project description:The identification of molecular characteristics that define metastatic disease is a primary research focus across numerous types of malignancies. Understanding the mechanisms that drive metastatic foci, which diverge significantly from the biology of primary tumors, and identifying new biomarkers specifically associated with metastatic disease, is of critical importance in oncology. Consequently, the characterization of the stroma associated with metastatic foci has been largely unexplored and remains an area requiring significant investigation. We identified a detailed transcriptional profile of the stromal compartment within primary tumors and corresponding metastatic foci using spatially resolved approaches. The identified stromal Met signature may serve as a prognostic biomarker and provide insights into the molecular mechanisms underlying the metastatic potential of the tumor microenvironment.
2024-08-04 | GSE273439 | GEO
Project description:Background: Robust prognostic stratification of patients with oropharyngeal squamous cell carcinoma (OPSCC) is important for developing individualized treatment plans. This study was conducted to develop and validate a clinically feasible prognostic classifier based on transcriptome-wide gene expression profiles. Methods: Tumor tissues were collected from 208 OPSCC patients treated at Washington University in St. Louis and 115 OPSCC patients treated at Vanderbilt University, used for model training and validation, respectively. OPSCC patients (n = 70) from the TCGA cohort were also included for independent validation. Based on RNA-seq profiling data, Cox proportional hazards regression analysis was performed to identify genes associated with disease outcomes. Then, Lasso-penalized multivariate survival models were constructed to identify biomarker genes for developing a prognostic gene signature. Findings: A 60-gene signature was identified by RNA-seq profiling analysis. Computed risk score of the gene signature was significantly predictive of 5-year overall survival of the training cohort (Hazard ratio (HR) 28.32, P = 4.3E-41). Subgroup analysis stratified by HPV status revealed that the signature was prognostic in HPV-positive OPSCC patients (HR 30.55, P = 7.0E-37) and was independent of clinical features. Importantly, the gene signature was validated in two independent patient cohorts, including the TCGA cohort (HR 3.94, P = 0.0018) and the Vanderbilt cohort (HR 8.50, P = 5.7E-09) for overall survival. Conclusions: The prognostic gene signature is a robust tool for risk stratification of OPSCC patients. The signature remains prognostic among HPV-positive OPSCC patients.
2021-04-13 | GSE171898 | GEO