Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Study of Target-Guided Chemotherapy in Metastatic Colorectal Patients

ABSTRACT: Treatment options for patients with colorectal cancer (CRC) have increased in the last years. However, there are no validated prospective molecular markers in CRC to select which agents are better to treat any individual case. The conventional first-line treatment in CRC patients in clinical studies get a proportion of patients free of progression at 12 months ranging from 35-40% with a median of 9 months of free disease progression. The aim of this study is to demonstrate that the identification of therapeutic targets in real time and their prospectively use to customize the treatment get a proportion of colorectal metastatic patients patients free of progression disease at 12 months of 50%.

DISEASE(S): Colon Cancer,Disease Progression,Progression Free Survival

PROVIDER: 2114261 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

ACCESS DATA

Json Xml

Similar Datasets

Newly diagnosed multiple myeloma patients with poor response to standard therapy

Project description:In this study, we analyzed transcriptome sequencing data to compare NDMM patients who were poor responders to the standard treatment approach (progression free survival < 24 months) to patients who were standard responders (progression free survival > 24 months).

2024-07-17 | GSE267013 | GEO

RNA expression profiles of HER2-positive advanced gastric or gastroesophageal junction cancer and healthy gastric mucosa control FFPE samples

Project description:A subgroup of patients with HER2-positive metastatic gastric and gastroesophageal junction cancers shows long-term response under trastuzumab maintenance monotherapy. Obviously, HER2 status alone is not able to identify these patients. We performed this study to identify potential new prognostic biomarkers for this long-term responding patient group. Tumor samples of 18 patients with HER2-positive metastatic gastric and gastroesophageal junction cancer who underwent trastuzumab treatment were retrospectively collected from multiple centers. Patients were divided into long-term responding (n=6) or fast-progression group (n=12) according to progression-free survival (PFS≥12 months vs PFS<12 months).We performed microarray-based gene expression analysis to investigate differences in immune cell populations between the patient groups.

2023-06-05 | GSE220917 | GEO

A phase II study of sitravatinib combined with tislelizumab plus docetaxel for acquired resistance to PD-(L)1 in patients with advanced/metastatic non-small cell lung cancer

Project description:In this phase Ⅱ study, 13 patients with stage III/Ⅳ immune checkpoint inhibitors (ICIs) - acquired resistant non-small cell lung cancer (NSCLC) were treated with tislelizumab, sitravatinib, and docetaxel. The primary endpoint is a 6-month progression-free survival (PFS) rate. Although the target enrollment was not reached, the 6-month PFS rate among the enrolled patients was 58.9% (95% CI 0.234 - 0.825), with a median PFS of 7.589 months (95% CI 1.873 - 14.423) and a median OS of 17.150 months (95% CI 1.873 - not reached). The ORR was 58.3% (7 of 12 patients, 1 not evaluable), and the DCR was 100% (12 of 12 patients). Following treatment with sitravatinib, T-cell diversity (+0.435, p = 0.5) and the PSI of CD4⁺ T cells tend to increase (+21.948, p = 0.8438), whereas the PSI of CD8+ T cells declines (-174.16, p = 0.0938). High CD4⁺ T cells ΔPSI (>40) was associated with a strong trend of longer PFS (14.400 vs 7.6 months, p = 0.0499). In conclusion, sitravatinib combination therapy demonstrated promising clinical benefit and manageable safety in NSCLC patients with acquired resistance to ICIs.

2025-12-17 | GSE309446 | GEO

Epigenetic regulation of the homeobox gene MSX1 associates with platinum resistant disease in high grade serous epithelial ovarian cancer

Project description:Introduction: Although High Grade Serous Ovarian Cancer (HGSOC) is considered a chemo-responsive disease, a proportion of patients do not respond to platinum-based chemotherapy at presentation or have progression-free survival of <6 months. Validated biomarkers of lack of response would enable alternative treatment stratification for these patients and identify novel mechanisms of resistance. Methods: Differential DNA methylation was investigated in independent tumour sets using Illumina 27K HumanMethylation arrays and validated by bisulphite pyrosequencing. Gene expression was by Affymetrix arrays and qRT-PCR. The role of Msh homeobox 1 (MSX1) in drug sensitivity was investigated by gene reintroduction into ovarian cancer cell lines. Results: CpG sites at contiguous genomic locations within the MSX1 gene have significantly lower levels of methylation in HGSOC which recur by 6 months compared to after 12 months and/or with RECIST response (p<0.05, q<0.05). A decrease in methylation at these intragenic CpG sites was significantly correlated with decreased MSX1 gene expression. Low expression of MSX1 was associated with poor progression-free survival independent of known clinical prognostic features (p=0.014). Three mutant or wild-type TP53 expressing ovarian cancer cell lines, resistant to cisplatin, have reduced MSX1 expression compared to matched parental, platinum sensitive, lines. Re-expression of MSX1 in resistant lines led to cisplatin sensitisation, increased apoptosis, increased p21 and BAX expression. However, in two TP53-null cell lines, MSX1 failed to change cisplatin sensitivity. Conclusion: Hypomethylation of MSX1 is a biomarker of resistant HGSOC disease at presentation and identifies a novel mechanism of platinum drug resistance. Bisulphite converted DNA from the 86 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2

2015-11-26 | E-GEOD-75414 | biostudies-arrayexpress

Epigenetic regulation of the homeobox gene MSX1 associates with platinum resistant disease in high grade serous epithelial ovarian cancer

2015-11-26 | GSE75414 | GEO

Baseline gene expression profiling determines long-term benefit to programmed cell death protein 1 axis blockade

Project description:Treatment with immune checkpoint inhibitors has altered the course of malignant melanoma, with approximately half of the patients with advanced disease surviving for more than 5 years after diagnosis. Currently, there are no biomarker methods for predicting outcome from immunotherapy. Here, we obtained transcriptomic information from a total of 105 baseline tumor samples comprising two cohorts of patients with advanced melanoma treated with programed cell death protein 1 (PD-1)-based immunotherapies. Gene expression profiles were correlated with progression-free survival (PFS) within consecutive clinical benefit intervals (i.e., 6, 12, 18, and 24 months). Elastic net binomial regression models with cross validation were utilized to compare the predictive value of distinct genes across time. Lasso regression was used to generate a signature predicting long-term benefit (LTB), defined as patients who remain alive and free of disease progression at 24 months post treatment initiation. We show that baseline gene expression profiles were consistently able to predict long-term immunotherapy outcomes with high accuracy. The predictive value of different genes fluctuated across consecutive clinical benefit intervals, with a distinct set of genes defining benefit at 24 months compared to earlier outcomes. A 12-gene signature was able to predict LTB following anti-PD-1 therapy with an area under the curve (AUC) equal to 0.92 and 0.74 in the training and validation set, respectively. Evaluation of LTB, via a unique signature may complement objective response classification and characterize the logistics of sustained antitumor immune responses.

2022-10-21 | GSE215868 | GEO

DNA methylation signatures correlate with response to immune checkpoint inhibitors in metastatic melanoma

Project description:DNA methylation profiles were recently proposed to have predictive value in various solid tumors. Therefore, we analyzed DNA methylation profiles of patients with stage IV metastatic melanoma, receiving first-line immune checkpoint inhibitors (ICIs) and correlated those with radiological response (iRECIST). Overall, 81 tissue samples from 71 patients with metastatic melanoma (27 (38.0%) female, 44 (62.0%) male) were investigated; median progression free survival was 8.5 months (0 – 104.1 months) and median overall survival was 30.6 months (0 – 104.1 months), respectively. 29 (40.8%) patients achieved an objective response. DNA methylation analyses revealed signatures correlating with radiological response to ICIs. Based on the 500 mostly differentially methylated genes, three clusters were identified with the majority of responders being in cluster 1 (12/12) and cluster 2 (12/24), and non-responders in cluster 3 (39/45). Our findings indicate that tumor DNA methylation profiling may be used as a predictor for ICI-response in patients with metastatic melanoma.

2024-04-03 | GSE235122 | GEO

Nuclear DICKKOPF-1 as a biomarker of chemoresistance and poor clinical outcome in colorectal cancer

Project description:Sporadic colorectal cancer (CRC) insurgence and progression depend on the activation of Wnt/?-catenin signaling. Dickkopf (DKK)-1 is an extracellular inhibitor of Wnt/?-catenin signaling that also has undefined ?-catenin-independent actions. Here we report for the first time that a proportion of DKK-1 locates within the nucleus of healthy small intestine and colon mucosa, and of CRC cells at specific chromatin sites of active transcription. Moreover, we show that DKK-1 regulates several cancer-related genes including the cancer stem cell marker aldehyde dehydrogenase 1A1 (ALDH1A1) and Ral-binding protein 1-associated Eps domain-containing 2 (REPS2), which are involved in detoxification of chemotherapeutic agents. Nuclear DKK-1 expression is lost along CRC progression; however, it remains high in a subset (15%) of CRC patients (n = 699) and associates with decreased progression-free survival (PFS) after chemotherapy administration and overall survival (OS) [adjusted HR, 1.65; 95% confidence interval (CI), 1.23-2.21; P = 0.002)]. Overexpression of ALDH1A1 and REPS2 associates with nuclear DKK-1 expression in tumors and correlates with decreased OS (P = 0.001 and 0.014) and PFS. In summary, our findings demonstrate a novel location of DKK-1 within the cell nucleus and support a role of nuclear DKK-1 as a predictive biomarker of chemoresistance in colorectal cancer. Analysis of DKK-1 location and associated roles in human colon cancer cells and crypts of small and large bowel.

2015-05-13 | E-GEOD-31170 | biostudies-arrayexpress

Mucosal biopsies from groups Normal (NOR) and patients who underwent curative large bowel resection for colorectal cancer (M-CRC)

Project description:The challenge of preventing colorectal cancer (CRC) is the early identification of individuals whose apparently normal colorectal mucosa will develop cancer, because of inherited trait or environmental exposure. We sought to use genome-wide expression profiling of endoscopic biopsies to detect a signature of propensity for cancer. We performed oligonucleotide microarray analysis of normal appearing mucosa of the following cases: healthy individuals (NOR), disease-free carriers predisposed to HNPCC (hereditary non-polyposis CRC), disease-free patients who underwent curative large bowel resection for CRC 1 to 15 years earlier and patients with CRC (MCRC) (GSE23011). As test set we run on affymetrix arrays an independent set of mucosal biopsies of MCRC and NOR samples. This profiling is based on the analysis of 5 patients who underwent curative large bowel resection for CRC from 1 to 15 years before (MCRC samples), and 12 endoscopy-negative, asymptomatic individuals (NOR samples)

2013-11-30 | E-GEOD-23194 | biostudies-arrayexpress

Gene expression profile in relapsed or metastatic HNSCC patients treated with cetuximab and platinum therapy

Project description:First line chemotherapy with platinum and cetuximab is usually offered to RM-HNSCC pts. In the Extreme trial a median progression free survival (PFS) time of 5.6 months was reported. However, a small fraction of pts achieves a prolonged PFS (> than 12 months). Till now, no recognized predictive biological factor has been identified.

2016-08-01 | GSE65021 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data