Dose dependent expression of extracellular microRNAs in HCT116 colorectal cancer cells exposed to high dose rate ionizing radiation
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ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE184174 | GEO | 2021/09/16
REPOSITORIES: GEO
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Project description:Background: MicroRNAs (miRNAs) are small, non-coding, RNA molecules which regulate numerous cellular processes. Specific miRNA may be abnormally down-regulated or up-regulated in colorectal cancer and have been found associated with prognosis or response to treatments. However, no study has ever addressed their predictive role in rectal cancer. Therefore, we used microarray technology and RT-PCR to profile miRNA expression patterns in patients (pts) with rectal cancer, with the aim to identify a specific M-bM-^@M-^\signatureM-bM-^@M-^] associated with pathological complete response after neoadjuvant chemo-radiotherapy. Methods: 38 pts with locally advanced rectal cancer (cT3-4/N+) were treated with capecitabine-oxaliplatin and pelvic conformal radiotherapy (45 cGy) followed by surgery (after 6-8 weeks). Pathologic response was scored according to the tumor regression grade (TRG) scale. MiRNA expression profile was analysed by microarray on fresh frozen biopsies obtained before treatment start and confirmed by RT-PCR. The correlation between miRNA expression profile and the TRG coded as TRG1 (pathologic Complete Response-pCR) versus TRG >1 (no pCR) was assessed by statistical analysis methods specifically designed for this study. Findings: 14 miRNAs were selected by arrays analysis as differentially expressed in TRG1 pts and 13 were confirmed by RT-PCR. In particular, 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909*, miR-630 and miR-765) were significantly up-regulated in TRG1 pts, while 2 miRNAs were under -expressed (miR-1274b and miR-720). miR-622 and miR-630 showed 100% sensitivity and specificity in selecting TRG1 cases and were significantly correlated with EGFR (M-OM-^G2=11M-bM-^@M-"793; p= 0M-bM-^@M-"001) and TS expression (M-OM-^G2=10M-bM-^@M-"589; p= 0M-bM-^@M-"001). Interpretation: A set of 13 miRNAs is strongly associated with pathologic complete response and may represent a specific marker of response to chemo-radiotherapy in locally advanced rectal cancer. Experiments were performed on purified RNA from preoperatory biopsies of 38 patients with histological diagnosis of rectal adenocarcinoma invading through the intestinal wall and/or with pelvic lymph node involvement as evaluated by endorectal ultrasonography (uT3-T4 and/or uN+). Patients were treated with neoadjuvant chemo-radiotherapy (capecitabine + oxaliplatin in combination with 45 Gy of pelvic conformal radiotherapy). Patients have been divided in the following two groups: group A those who had obtained a pathologic complete response M-bM-^@M-^S TRG 1, including the patient without detectable disease who refused surgery, group B any pathologic response other than complete.
2012-04-24 | E-GEOD-29298 | biostudies-arrayexpress
Project description:Radiotherapy is one of the most common therapies for cancer. Approximately half of all cancer patients will receive radiotherapy at some point during treatment. Consequences of IR treatment are dose dependent and different sensitivity to IR of various types of cells is well established. To reduce the damage of IR to most sensitive cells of normal (noncancerous) tissue radiotherapy is administered as fractionated dose treatment applying radiation in ~2 Gy fractions every 24 hours, 5 times per week. However, during the therapy intrinsic and acquired tumor radioresistance may result in treatment failures. Comprehensive mechanisms of the resistance to irradiation as well as mechanisms of cellular response to fractionated dose IR remain unclear. Different gene expression patterns may be partially influenced by short ~22 nt non-coding RNA molecules called microRNAs (miRNAs) via translational regulation or RNA degradation mechanisms. Therefore, in the present study we evaluated global miRNA changes in murine Lewis lung carcinoma LLC1 cells following X-ray irradiation of single 2 Gy or 10 Gy and 2 Gy x 5 fractionated doses. Total RNA enriched in small noncoding RNAs was isolated from mouse Lewis lung carcinoma cells 4h after treatment of single (2 Gy or 10 Gy) or fractionated (5x2 Gy) ionizing radiation dose.
2016-07-07 | E-GEOD-84109 | biostudies-arrayexpress
Project description:Radiotherapy is one of the most common therapies for cancer. Approximately half of all cancer patients will receive radiotherapy at some point during treatment. Consequences of IR treatment are dose dependent and different sensitivity to IR of various types of cells is well established. To reduce the damage of IR to most sensitive cells of normal (noncancerous) tissue radiotherapy is administered as fractionated dose treatment applying radiation in ~2 Gy fractions every 24 hours, 5 times per week. However, during the therapy intrinsic and acquired tumor radioresistance may result in treatment failures. Comprehensive mechanisms of the resistance to irradiation as well as mechanisms of cellular response to fractionated dose IR remain unclear. Different gene expression patterns may be partially influenced by short ~22 nt non-coding RNA molecules called microRNAs (miRNAs) via translational regulation or RNA degradation mechanisms. Therefore, in the present study we evaluated global miRNA changes in murine Lewis lung carcinoma LLC1 cells following X-ray irradiation of single 2 Gy or 10 Gy and 2 Gy x 5 fractionated doses.
2016-07-07 | GSE84109 | GEO
Project description:<p>The biomarker development study consisted of two parts: discovery and validation. The first part was the discovery and verification phase of biomarkers using two different platforms: transcriptomic and miRNA. The salivary transcriptomes of 63 GC samples and 31 non-GC controls were profiled using Affymetrix HG U133+2.0 microarrays (Affymetrix, Santa Clara, CA). The identified exRNA candidates were verified by quantitative real-time PCR (RT-qPCR) using all 94 of the original samples. In the discovery phase for the miRNA biomarkers, 10 early-stage GC samples and 10 non-GC controls were selected. The salivary miRNAs of these samples (n=20) were profiled using the TaqMan MicroRNA Array (Applied Biosystems, Foster City, CA). MicroRNA candidates were verified using TaqMan miRNA Assay (Thermo Scientific, Grand Island, NY). The second part of the study was to validate these verified exRNA biomarker candidates with exRNA samples extracted from an independent cohort of 100 GC and 100 non-GC saliva samples. The cohort was not balanced for demographics on gender and smoking history but more accurately reflected the diagnostic setting where our proposed final model could be implemented.</p> <p>Reprinted from "Li F, Yoshizawa MJ, Kim K, Kanjanapangka J, Grogan T, Wang X, Elashoff D, Ishikawa S, Chia D, Liao W, Akin D, Yan X, Lee M, Choi R, Kim S, Kang S, Bae J, Sohn T, Lee J, Choi M, Min B, Lee J, Kim J, Kim Y, Kim S, Wong D. (2018) Development and Validation of Salivary Extracellular RNA Biomarkers for Noninvasive Detection of Gastric Cancer. Clin Chem. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/30097497">30097497</a> DOI: 10.1373/clinchem.2018.290569", with permission from American Association for Clinical Chemistry (United States). </p>
| phs001767 | dbGaP
Project description:Severe xerostomia is noted in the majority of patients irradiated for oropharyngeal cancer (OPC). Extracellular microRNAs (miRNAs) may serve as effective tools allowing prediction of radiation-related toxicity. The aim of this study was to create an efficient prognostic miRNA-based test for severe, patient-rated xerostomia 3 months after primary treatment. This prospective study enrolled OPC patients treated between 2016 and 2018 in three centers in Poland. The primary endpoint was severe (grade ≥3) xerostomia as assessed by the EORTC H&N-35 questionnaires. Initially, a group of 10 patients with severe xerostomia was randomly selected and matched with a comparative group of 10 patients without severe xerostomia. Samples were collected before RT, after receiving 20 Gy and within 24 hours after treatment completion. qPCR arrays (QIAGEN, Hilden, Germany) were used to quantify expression levels of 752 miRNAs in the serum at all timepoints. The resulting logistic-regression based model was validated in additional 60 patients: 30 with grade >3 xerostomia and 30 without. Of 152 eligible patients, we successfully recruited 111 patients. Severe xerostomia 3 months after treatment was reported by 63 patients (56.8%). Mean dose delivered to parotid glands was higher in both exploratory and validation cohort. The model based on miR-185-5p and miR-425-5p expression levels measured before the start of radiotherapy had AUC 0.96 (95% CI: 0.88-1.00). The model based on the same miRNAs remained robust when parameters were measured after 20 Gy (AUC 0.90 (95% CI: 0.75-1.00)). These results were confirmed in the validation group. In the validation group pre-radiotherapy model application yielded 73.3% sensitivity and 80.0% specificity. In the samples taken after 20 Gy, the same two miRNAs yielded 67.7% sensitivity and 72.4% specificity. The model including pretreatment miR-185-5p and miR-425-5p levels together with mean parotid dose, yielded 90.0% sensitivity and 80.0% specificity. In the validation cohort, this model yielded 80.6 % sensitivity and 55.2 % specificity. The model based on miRNA levels measured after 20 Gy and mean parotid dose had 80.0 % sensitivity and 100% specificity in the exploratory group. In the validation cohort its performance fell to 71.0 % sensitivity and 58.6 % specificity. Serum expression levels of miR-425-5p and miR-185-5p measured before the start of radiotherapy or during therapy (after 20 Gy) had a significant prognostic value for the occurrence of severe xerostomia 3 months after treatment completion. The variability explained by miRNAs appears to be, at least partially, independent from the one related to the dosimetric data.
2021-08-16 | GSE182178 | GEO
Project description:Exposure to high-dose radiation causes life-threatening serious intestinal damage. Histological analysis is the most accurate method for judging the extent of intestinal damage after death. However, it is difficult to predict the extent of intestinal damage to body samples. Here we focused on extracellular microRNAs (miRNAs) released from cells and investigated miRNA species that increased or decreased in serum and feces using a radiation-induced intestinal injury mouse model. A peak of small RNA of 25–200 nucleotides was detected in mouse serum and feces 72 h after radiation exposure, and miRNA presence in serum and feces was inferred. MiRNAs expressed in the small intestine and were increased by more than 2.0-fold in serum or feces following a 10 Gy radiation exposure were detected by microarray analysis and were 4 in serum and 19 in feces. In this study, miR-375-3p, detected in serum and feces, was identified as the strongest candidate for a high-dose radiation biomarker in serum and/or feces using a radiation-induced intestinal injury model.
2023-12-15 | GSE247876 | GEO
Project description:Our in vivo study measures miRNA and gene expression changes in human blood cells in response to ionizing radiation in order to develop miRNA signatures that can be used as biomarkers for radiation exposure. Blood was collected from 8 radiotherapy patients immediately prior to and at 4 h after total body irradiation with 1.25 Gy X-rays. Both miRNA and gene expression changes were measured by means of quantitative PCR and microarray hybridization, respectively. Patients were in complete remission at the time of blood collection. Out of 223 differentially expressed genes, 37 were both downregulated and predicted targets of the upregulated miRNAs. Both miRNA and gene control of biological processes such as hemopoiesis and the immune response is increased after irradiation, whereas metabolic processes are underrepresented among all differentially expressed genes and the genes controlled by miRNAs. Sixteen human whole-blood samples were included in this study. Eight samples were collected shortly before total body irradiation. The other 8 samples were collected at 4 h after total body irradiation with 1.25 Gy X-rays.
2010-08-05 | E-GEOD-23393 | biostudies-arrayexpress
Project description:Our in vivo study measures miRNA and gene expression changes in human blood cells in response to ionizing radiation in order to develop miRNA signatures that can be used as biomarkers for radiation exposure. Blood was collected from 8 radiotherapy patients immediately prior to and at 4 h after total body irradiation with 1.25 Gy X-rays. Both miRNA and gene expression changes were measured by means of quantitative PCR and microarray hybridization, respectively. Patients were in complete remission at the time of blood collection. Out of 223 differentially expressed genes, 37 were both downregulated and predicted targets of the upregulated miRNAs. Both miRNA and gene control of biological processes such as hemopoiesis and the immune response is increased after irradiation, whereas metabolic processes are underrepresented among all differentially expressed genes and the genes controlled by miRNAs.
2010-08-05 | GSE23393 | GEO
Project description:Background: MicroRNAs (miRNAs) are small, non-coding, RNA molecules which regulate numerous cellular processes. Specific miRNA may be abnormally down-regulated or up-regulated in colorectal cancer and have been found associated with prognosis or response to treatments. However, no study has ever addressed their predictive role in rectal cancer. Therefore, we used microarray technology and RT-PCR to profile miRNA expression patterns in patients (pts) with rectal cancer, with the aim to identify a specific “signature” associated with pathological complete response after neoadjuvant chemo-radiotherapy. Methods: 38 pts with locally advanced rectal cancer (cT3-4/N+) were treated with capecitabine-oxaliplatin and pelvic conformal radiotherapy (45 cGy) followed by surgery (after 6-8 weeks). Pathologic response was scored according to the tumor regression grade (TRG) scale. MiRNA expression profile was analysed by microarray on fresh frozen biopsies obtained before treatment start and confirmed by RT-PCR. The correlation between miRNA expression profile and the TRG coded as TRG1 (pathologic Complete Response-pCR) versus TRG >1 (no pCR) was assessed by statistical analysis methods specifically designed for this study. Findings: 14 miRNAs were selected by arrays analysis as differentially expressed in TRG1 pts and 13 were confirmed by RT-PCR. In particular, 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909*, miR-630 and miR-765) were significantly up-regulated in TRG1 pts, while 2 miRNAs were under -expressed (miR-1274b and miR-720). miR-622 and miR-630 showed 100% sensitivity and specificity in selecting TRG1 cases and were significantly correlated with EGFR (χ2=11•793; p= 0•001) and TS expression (χ2=10•589; p= 0•001). Interpretation: A set of 13 miRNAs is strongly associated with pathologic complete response and may represent a specific marker of response to chemo-radiotherapy in locally advanced rectal cancer.
2012-04-25 | GSE29298 | GEO
Project description:Radiotherapy remains a standard treatment for colorectal cancer. The clinical significance of the conventional treatment is based on accumulated dose and usually consists of single daily irradiations of 1.8 - 2 Gy fractions. However the repopulation of cancer cells during and/or after the treatment suggests that the surviving fraction of cells acquire the radioresistance to cancer therapy. It has been determined a number of radioresistance markers, but only limited data exist on the acquisition of the resistance to fractionated radiation therapy. This research provides the genomic data of gene expression changes in colorectal cancer cell HCT116 line following single and multiple fractions of irradiation, aiming to identify particular genes associated with the effect of fractionated radiotherapy.
2017-08-29 | GSE103178 | GEO