Gene expression following ionising radiation: Identification of biomarkers for dose estimation and prediction of individual response

Kabacik, Sylwia; Mackay, Alan; Tamber, Narinder; Manning, Grainne; Finnon, Paul; Paillier, Francois; Ashworth, Alan; Bouffler, Simon; Badie, Christophe

doi:10.3109/09553002.2010.519424

Cited by 136 publications

(116 citation statements)

References 45 publications

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“…5D) a pro-apoptotic gene, were shown to be exclusively induced in response to 1 Gy. These genes were extensively validated in response to ionizing radiation (40)(41)(42)(43)(44) and shown to be activated in response to p53 signaling (45), where as our results showed upregulation in the phosphorylated form of p53 in response to 1 Gy (Fig. 6).…”

Section: Discussionmentioning

confidence: 82%

Low doses of ionizing radiation induce immune-stimulatory responses in isolated human primary monocytes

El‐Saghire

Michaux

Thierens

et al. 2013

International Journal of Molecular Medicine

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Abstract. The health effects arising from exposure to low doses of ionizing radiation are of particular concern, mainly due to the increased application of diagnostic and therapeutic X-ray modalities. The mechanisms behind the cell and tissue responses to low doses remain to be elucidated. Accumulating evidence suggests that low doses of ionizing radiation induce activation of the immune response; however, the processes involved have yet to be adequately investigated. Monocytes are key players in the induction of an immune response. Within the context of this study, we investigated the activation of toll-like receptors (TLRs), mitogen-activated protein kinases (MAPKs) and NF-κB signaling in isolated human primary monocytes in response to low doses (0.05 and 0

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Section: Discussionmentioning

confidence: 82%

Low doses of ionizing radiation induce immune-stimulatory responses in isolated human primary monocytes

El‐Saghire

Michaux

Thierens

et al. 2013

International Journal of Molecular Medicine

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“…Cells were sham irradiated or 2 Gy X irradiated and collected at various time points ranging from 15 min up to 24 h postirradiation. We studied the expression of ten protein-coding genes, which were previously reported to be responsive to radiation either in stimulated T lymphocytes (14) or blood (15): CDKN1A, SESN1, ATF3, MDM2, CCNB1, DDB2, FDXR, CCNG1, BBC3 (also known as PUMA) and GADD45A. The results for mRNA expression are shown in Fig.…”

Section: Temporal Response To Ionizing Radiationmentioning

confidence: 99%

“…With the development of microarray technology that enables screening of hundreds of genes simultaneously (5), it became clear that many more genes are modulated in response to radiation exposure (6-13), mostly in a TP53-dependent manner. Gene expression changes after exposure to radiation are now well documented in human blood (14), even after low-dose exposures (15).…”

Section: Introductionmentioning

confidence: 99%

Time, Dose and Ataxia Telangiectasia Mutated (ATM) Status Dependency of Coding and Noncoding RNA Expression after Ionizing Radiation Exposure

et al. 2015

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“…Many genes identified as radiation induced in our analysis were previously known to be radiation responsive in humans including CREM, BNIP3, FAS, TNFRSF11B, IFITM1, LGALS3PB, COX7B and SESN1 (26)(27)(28)(29), indicating the conservation of the radiation responsiveness of many genes in this p53-deficient mouse model. Using the program DAVID [Database for Annotation, Visualization and Integrated Discovery (30,31); http:// david.abcc.ncifcrf.gov], the gene ontology categories that were significantly overrepresented relative to chance in the set of all radiation-induced genes included: "protein catabolic process" (P = 3.40 × 10 −9 ); "apoptosis" (P = 3.45 × 10 −5 ); "cell death" (P = 1.17 × 10 −4 ) and "macromolecule catabolic process" (P = 8.24 × 10 −8 ).…”

Section: Identification Of Radiation-responsive Genesmentioning

confidence: 90%

Radiation-induced Gene Signature Predicts Pathologic Complete Response to Neoadjuvant Chemotherapy in Breast Cancer Patients

Chao

Balletta

et al. 2012

International Journal of Radiation Oncology*Biology*Physics

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The identification of biomarkers predictive of neoadjuvant chemotherapy response in breast cancer patients would be an important advancement in personalized cancer therapy. In this study, we hypothesized that due to similarities between radiation-and chemotherapy-induced cellular response mechanisms, radiation-responsive genes may be useful in predicting response to neoadjuvant chemotherapy. Murine p53 null breast cancer cell lines representative of the luminal, basal-like and claudin-low human breast cancer subtypes were irradiated to identify radiationresponsive genes across subtypes. These murine tumor radiation-induced genes were then converted to their human orthologs, and subsequently tested as a predictor of pathologic complete response (pCR), which was validated on two independent published neoadjuvant chemotherapy datasets of genomic data with chemotherapy response. A radiation-induced gene signature consisting of 30 genes was identified on a training set of 337 human primary breast cancer tumor samples that was prognostic for survival. Mean expression of this signature was calculated for individual samples on two independent published datasets and was found to be significantly predictive of pCR. Multivariate logistic regression analysis in both independent datasets showed 1 Address for correspondence: Leo W. Jenkins Cancer Center, The Brody School of Medicine at East Carolina University, 600 Moye Boulevard, Greenville, NC 27834; oh.daniel.s@gmail.com. Supplementary Fig. S1. http://dx.doi.org/10.1667/RR13485.1.S1; Gene cluster A shown Fig. 3 (upper left) significantly enriched for genes involved in wound and inflammatory response as determined by DAVID. Supplementary Fig. S2. http://dx.doi.org/10.1667/RR13485.1.S1; Gene cluster B from Fig. 3 (upper left) significantly enriched for genes involved in M phase, mitotic cell cycle and ribosome as determined by DAVID. Supplementary Fig. S3. http://dx.doi.org/10.1667/RR13485.1.S1; Gene cluster C from Fig. 3 (upper left) significantly enriched for genes involved in muscle contraction, muscle cell development, and myofibril assembly as determined by DAVID. Supplementary Fig. S4. http://dx.doi.org/10.1667/RR13485.1.S1; Gene cluster D from Fig. 3 (upper left) significantly enriched for genes involved in positive regulation of mesenchymal cell proliferation, blood vessel development and cell motion as determined by DAVID. Supplementary Fig. S5. http://dx.doi.org/10.1667/RR13485.1.S1; Gene cluster E from Fig. 3 (upper left) significantly enriched for genes involved in zinc ion and DNA binding as determined by DAVID. SUPPLEMENTARY INFORMATION HHS Public Access

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Gene expression following ionising radiation: Identification of biomarkers for dose estimation and prediction of individual response

Cited by 136 publications

References 45 publications

Low doses of ionizing radiation induce immune-stimulatory responses in isolated human primary monocytes

Low doses of ionizing radiation induce immune-stimulatory responses in isolated human primary monocytes

Time, Dose and Ataxia Telangiectasia Mutated (ATM) Status Dependency of Coding and Noncoding RNA Expression after Ionizing Radiation Exposure

Radiation-induced Gene Signature Predicts Pathologic Complete Response to Neoadjuvant Chemotherapy in Breast Cancer Patients

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