Gene expression data of locally advanced rectal cancer patients by KRAS status
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE170999 | GEO | 2021/03/29
REPOSITORIES: GEO
Similar Datasets
Project description:Gene expression data of locally advanced rectal cancer patients by KRAS status
| PRJNA718067 | ENA
Project description:Locally advanced rectal cancer characterized by multiplex kinase activity profiling
2010-08-05 | E-TABM-913 | biostudies-arrayexpress
Project description:Mutations of the KRAS oncogene are predictive for resistance to treatment with antibodies against the epithelial growth factor receptor in patients with colorectal cancer. Overcoming this therapeutic dilemma could potentially be achieved by the introduction of drugs that inhibit signaling pathways that are activated by KRAS mutations. To comprehensively identify such signaling pathways we profiled pretreatment biopsies from 65 patients with locally advanced rectal cancer – 30 of which carried mutated KRAS - using global gene expression microarrays. By comparing all tumor tissues exclusively to matched normal mucosa, we could improve assay sensitivity, and identified a total of 22,297 features that were differentially expressed (adjusted p-value p<0.05) between normal mucosa and cancer, including several novel potential rectal cancer genes. We then used this comprehensive description of the rectal cancer transcriptome as the baseline for identifying KRAS-dependent alterations. The presence of activating KRAS mutations resulted in significant upregulation of 13 genes (adjusted p-value < 0.05), among them DUSP4, a MAP-kinase phosphatase, and SMYD3, a histone methyltransferase. Inhibition of the expression of both genes has been achieved therapeutically with the MEK1-inhibitor PD98059 and the antibacterial compound Novobiocin, respectively, suggesting a potential approach to overcome resistance to treatment with antibodies against the epithelial growth factor receptor in patients with KRAS-mutant rectal carcinomas. Paired samples of tumor and mucosa from a total of 65 patients, i.e. 130 arrays
2011-03-11 | E-GEOD-20842 | biostudies-arrayexpress
Project description:Mutations of the KRAS oncogene are predictive for resistance to treatment with antibodies against the epithelial growth factor receptor in patients with colorectal cancer. Overcoming this therapeutic dilemma could potentially be achieved by the introduction of drugs that inhibit signaling pathways that are activated by KRAS mutations. To comprehensively identify such signaling pathways we profiled pretreatment biopsies from 65 patients with locally advanced rectal cancer – 30 of which carried mutated KRAS - using global gene expression microarrays. By comparing all tumor tissues exclusively to matched normal mucosa, we could improve assay sensitivity, and identified a total of 22,297 features that were differentially expressed (adjusted p-value p<0.05) between normal mucosa and cancer, including several novel potential rectal cancer genes. We then used this comprehensive description of the rectal cancer transcriptome as the baseline for identifying KRAS-dependent alterations. The presence of activating KRAS mutations resulted in significant upregulation of 13 genes (adjusted p-value < 0.05), among them DUSP4, a MAP-kinase phosphatase, and SMYD3, a histone methyltransferase. Inhibition of the expression of both genes has been achieved therapeutically with the MEK1-inhibitor PD98059 and the antibacterial compound Novobiocin, respectively, suggesting a potential approach to overcome resistance to treatment with antibodies against the epithelial growth factor receptor in patients with KRAS-mutant rectal carcinomas.
2011-03-11 | GSE20842 | GEO
Project description:Understanding transcriptional changes in locally advanced rectal cancer which are therapy-related and dependent upon tumour regression will drive stratified medicine in the rectal cancer paradigm
2018-11-01 | GSE94104 | GEO
Project description:locally advanced rectal cancer (LARC) patients were sorted according to their radio-responsiveness. Patients were categorized into two groups—complete response (n = 3) and poor response (n = 3)—based on the tumor regression grade. Expression profiles for each group were obtained using RNA-seq on a HiSeq 4000 system (Illumina).
2023-03-01 | GSE226034 | GEO
Project description:The study objective was to find new biomarkers of treatment response and adverse events in patients receiving neoadjuvant therapy for locally advanced rectal cancer. Patients received neoadjuvant chemotherapy (NACT) followed by chemoradiotherapy (CRT) and underwent treatment evaluation four weeks after CRT completion. Radical pelvic surgery was planned 2-4 weeks later. Patients were scored for treatment adverse events, according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, throughout the neoadjuvant treatment course, including at NACT and CRT completion. Treatment response was assessed by histologic ypTN staging and tumor regression grade (TRG) scoring, as well as progression-free survival (time from Inclusion date to Date of local relapse or Date of metastatic disease, whichever came first) recorded for five years after surgery.
2016-04-21 | GSE65622 | GEO
Project description:Samples were prospectively collected during colonoscopic examination from 46 rectal cancer patients before starting preoperative chemoradiotherapy. The expression profiles were determined using Affymetrix Human Genome U133 Plus 2.0 arrays. Comparison between the sample groups allow to identify a set of discriminating genes that can be used for prediction of the response to radiotherapy in rectal cancer. Specimens from 46 rectal cancer patients who approved to receive preoperative chemoradiotherapy were studied. We prospectively collected biopsy specimens during colonoscopic examination from rectal cancer before starting preoperative chemoradiotherapy. Specimens from tumors were snap-frozen in liquid nitrogen and stored at -80 C until use. Paralleled tumor specimens were formalin fixed and paraffin embedded for histologic examination and other specimens were used for RNA extraction. RNA was extracted from tumor tissue using frozen samples. The patients provided written, informed consent to the collection of specimens, and the local Ethics Committee approved the study protocol. All patients received a total dose of 50.4 Gy of radiation, UFT(300-500mg/day) and LV (75mg/day) and underwent standardized curative resection, following an interval of 4 weeks after chemoradiotherapy.
2013-01-29 | E-GEOD-35452 | biostudies-arrayexpress
Project description:Most patients with locally advanced rectal cancer (LARC) present incomplete pathological response (pIR) to neoadjuvant chemoradiotherapy (nCRT). Despite the efforts to predict treatment response using tumor-molecular features, as differentially expressed genes, no molecule has proved to be a strong biomarker. The tumor secretome analysis is a promising strategy for biomarkers identification, which can be assessed using transcriptomic data. Here, we performed transcriptomic-based secretome analysis to select potentially secreted proteins using an in silico approach. The tumor expression profile of 28 LARC biopsies carefully selected and collected before nCRT was compared with normal rectal tissues (NT). The expression profile showed no significant differences between cases with complete (pCR) and incomplete response to nCRT. Genes with increased expression (pCR = 106 and pIR = 357) were used for secretome analysis based on public databases (Vesiclepedia, Human Cancer Secretome Database and Plasma and Proteome Database). Seventeen potentially secreted candidates (pCR=1, pIR=13 and 3 in both groups) were further investigated in two independent datasets (TCGA and GSE68204) confirming their over-expression in LARC. The potential secreted biomarkers were also confirmed as associated with the nCRT response (GSE68204). These putative proteins are candidates to be assessed in liquid biopsies aiming a personalized treatment in LARC patients.
2019-07-01 | GSE123390 | GEO
Project description:BackgroundMutated KRAS may indicate an invasive nature and predict prognosis in locally advanced rectal cancer (LARC). We aimed to establish a radiomic model using pretreatment T2W MRIs to predict KRAS status and explore the association between the KRAS status or model predictions and lung metastasis.MethodsIn this retrospective multicentre study, LARC patients from two institutions between January 2012 and January 2019 were randomly divided into training and testing cohorts. Least absolute shrinkage and selection operator (LASSO) regression and the support vector machine (SVM) classifier were utilized to select significant radiomic features and establish a prediction model, which was validated by radiomic score distribution and decision curve analysis. The association between the model stratification and lung metastasis was investigated by Cox regression and Kaplan‒Meier survival analysis; the results were compared by the log-rank test.ResultsOverall, 103 patients were enrolled (73 and 30 in the training and testing cohorts, respectively). The median follow-up was 38.1 months (interquartile range: 26.9, 49.4). The radiomic model had an area under the curve (AUC) of 0.983 in the training cohort and 0.814 in the testing cohort. Using a cut-off of 0.679 defined by the receiver operating characteristic (ROC) curve, patients with a high radiomic score (RS) had a higher risk for lung metastasis (HR 3.565, 95% CI 1.337, 9.505, p = 0.011), showing similar predictive performances for the mutant and wild-type KRAS groups (HR 3.225, 95% CI 1.249, 8.323, p = 0.016, IDI: 1.08%, p = 0.687; NRI 2.23%, p = 0.766).ConclusionsWe established and validated a radiomic model for predicting KRAS status in LARC. Patients with high RS experienced more lung metastases. The model could noninvasively detect KRAS status and may help individualize clinical decision-making.
| S-EPMC10717608 | biostudies-literature