Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA386933 | ENA |
REPOSITORIES: ENA
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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:Rectal cancer (RC) accounts for one-third of colorectal cancer (CRC), and 40% of these are locally advanced rectal cancer (LARC) at diagnosis. The use of neoadjuvant chemoradiotherapy (nCRT) significantly reduces the rate of local recurrence compared to adjuvant therapy or surgery alone. However, after nCRT, up to 40-60% of patients show a poor pathological response, while only about 20% achieve a pathological complete response. In this scenario, the identification of novel predictors of tumor response to nCRT are urgently needed to reduce LARC mortality, and to spare poorly responding patients from unnecessary treatments. Therefore, by combining gene and microRNA expression datasets with proteomic data from LARC patients, we developed an integrated network centered on seven hub-genes putatively involved in the response to nCRT. In an independent validation cohort of LARC patients, we confirmed the differential expression of NFKB1, TRAF6 and STAT3 depending on a response to nCRT. In addition, the functional enrichment analysis also revealed that these genes are strongly related to hallmarks of cancer and inflammation, whose dysfunction may causatively affect LARC patient’s response to nCRT. Furthermore, by constructing the transcription factor-module network, we hypothesized a protective role of POU2F3 gene, which could be used as a new drug target in LARC patients. Finally, we identified and in vitro tested entinostat, a histone deacetylase (HDAC) inhibitor, as a chemical compound that could be combined with classical therapeutic regimen in order to design more efficient therapeutic strategies in LARC.
2023-01-05 | PXD035408 | Pride
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.
2013-01-29 | GSE35452 | GEO
Project description:Neoadjuvant chemoradiation therapy (CRT) is a widely used preoperative treatment strategy for locally advanced rectal cancer (LARC). However, a few studies have evaluated the molecular changes caused by neoadjuvant CRT in these cancer tissues. Here, we aimed to investigate changes in immunotherapy-related immunogenic effects in response to preoperative CRT in LARC. We analyzed 60 pairs of human LARC tissues before and after irradiation from three independent LARC cohorts, including a LARC patient RNA sequencing (RNA-seq) dataset from our cohort and GSE15781 and GSE94104 datasets. Gene ontology analysis showed that preoperative CRT significantly enriched the immune response in LARC tissues. Moreover, gene set enrichment analysis revealed six significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways associated with downregulated genes, including mismatch repair (MMR) genes, in LARC tissues after CRT in all three cohorts. Radiation also induced apoptosis and downregulated various MMR system-related genes in three colorectal cancer cells. One patient with LARC showed a change in microsatellite instability (MSI) status after CRT, as demonstrated by the loss of MMR protein and PCR for MSI. Moreover, CRT significantly increased tumor mutational burden in LARC tissues. CIBERSORT analysis revealed that the proportions of M2 macrophages and CD8 T cells were significantly increased after CRT in both the RNA-seq dataset and GSE94104. Notably, preoperative CRT increased various immune biomarker scores, such as the interferon-γ signature, the cytolytic activity and the immune signature. Taken together, our findings demonstrated that neoadjuvant CRT modulated the immune-related characteristics of LARC, suggesting that neoadjuvant CRT may enhance the responsiveness of LARC to immunotherapy.
2023-05-31 | GSE233517 | GEO
Project description:Predicting multi-class responses to preoperative chemoradiotherapy in rectal patients
| PRJNA202902 | ENA
Project description:The goal of this work is to find robust predictors of tumor response to preoperative chemoradiotherapy in LARC patients. Preoperative chemoradiotherapy (pCRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC). However, tumour response to pCRT is not uniform and there are no effective predictive methods. This study investigated whether specific gene and miRNA expression is associated with response to pCRT. Tissue biopsies were obtained from patients before pCRT and resection. Gene and miRNA expression was analyzed using one-color microarrays technique comparing signatures between responders (R) and not responders(NR), as measured by tumour regression grade (TRG). Two groups composed by 38 “exploration cohort” and 21 “validation cohort” LARC patients respectively were considered, for a total of 32 NR and 27 R patients. In the first cohort, SAM Two Class identified 256 genes and 29 miRNAs differentially expressed between NR and R. The anti-correlation analysis showed that the same 8 miRNA interacted with different networks of transcripts. The miR-630 appeared only with NR patients and was anti-correlated with a single transcript: RAB5B. After PAM, resulted as strong predictors of tumour responsen the following 8 transcripts: TMEM188, ITGA2, NRG, TRAM1, BCL2L13, MYO1B, KLF7 and GTSE1. Using this gene set, an unsupervised cluster analysis applied to the second cohort assigned the patients to the NR or R group with 85.7% accuracy with a sensitivity of 90% and a specificity of 82%. All the three parametres reached 100% when the two cohorts were considered together.
2016-04-22 | GSE68204 | GEO
Project description:The identification of surrogate single nucleotide polymorphism (SNP) markers that can predict responses to preoperative chemoradiotherapy (CRT) in rectal cancer patients. Genome-wide association studies in clinical populations are theoretically capable of identifying markers that are capable of tumor regression after CRT. We used Affymetrix’s SNP Array 6.0 to detail genetic polymorphism of patient’s group showing differential responsiveness to preoperative CRT and profiled SNP biomarkers.
2012-12-31 | GSE35282 | GEO
Project description:Neoadjuvant chemoradiotherapy (CRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC). However, there are no good predictive methods. This study investigated whether specific lncRNA expression is associated with response to CRT. Tissue biopsies were obtained from patients before CRT. LncRNA expression was analyzed using one-color microarrays technique comparing signatures between good respondersand poor responders, as measured by tumour regression grade (TRG).
2020-02-22 | GSE145666 | GEO
Project description:Cancer-associated fibroblasts (CAFs) are an important component of the desmoplastic stroma in rectal cancer. Preoperative chemoradiotherapy plays a pivotal role in the management of locally advanced rectal cancer. Patient-derived CAFs were used to evaluate the response to radiotherapy and its consequent impact on colorectal cancer cells (COLO320DM). COLO320DM cells were seeded and 24 hours later 1.8Gy irradiated. Subsequently, 24h later COLO320DM cells were treated with the secretome of 10x 1.8Gy irradiated CAFs or sham treated CAFs in 0.5% of serum. RNA was isolated 6 hours or 48 hours later.
2017-11-01 | E-MTAB-5364 | 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