Genomic approach to refine prognosis for adjuvant therapy in early stage non-small cell lung carcinoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE3593 | GEO | 2006/08/10
SECONDARY ACCESSION(S): PRJNA93691
REPOSITORIES: GEO
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Project description:Abstract from paper - Potti A, et al Experiment Overall Design: Retrospective analysis of approximately 200 samples obtained from Duke, ACOSOG and CALGB to develop a Lung metagene predictor that would then be used to assess risk of recurrence and thus identify high risk patients with stage Ia non-small cell carcinoma who would be candidates for adjuvant chemotherapy
2008-06-12 | E-GEOD-3593 | biostudies-arrayexpress
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Project description:Purpose: Despite the benefits of estrogen receptor (ER)-targeted endocrine therapies in breast cancer, many tumors develop resistance. MicroRNAs (miRNAs) have been suggested as promising biomarkers and we here evaluated whether a miRNA profile could be identified, sub-grouping ER+ breast cancer patients treated with adjuvant Tamoxifen with regards to probability of recurrence. Experimental design: Global miRNA analysis was performed on 152 ER+ primary tumors from high-risk breast cancer patients with an initial discovery set of 52 patients, followed by 2 independent test sets (N=60 and N=40). All patients had received adjuvant Tamoxifen as mono-therapy (median clinical follow-up: 4.6 years) and half had developed distant recurrence (median time-to-recurrence: 3.5 years). MiRNA expression was examined by unsupervised hierarchical clustering and supervised analysis, including clinical parameters as co-variables.
2012-04-19 | GSE37405 | GEO
Project description:The activity of the potent nasal adjuvant flagellin depends on initial activation of airway epithelilal cells. This study aims at investigating the immune cells involved in the antigen presentation within the respiratory tract. First, microarrays characterized that activation/recruitment of immune cells was the main signature of flagellin activation in lung. Neutrophils and classical monocytes were strongly recruited into the lungs and take up antigen upon nasal administration of flagellin. In contrast, the numbers of lung CD11b+ or CD103+ DC and alveolar macrophages were not enhanced although these cells were very efficient in antigen uptake. Our experiments showed that CD11b+ DC but not monocytes, PMN, CD103+ DC are not essential for the adjuvant effect. Flagellin signaling enhanced the functional activation of lung CD11b+ conventional DC and their migration to the lymph nodes. Using Cd11c-DTR mice, CD11b+ DC from lymph nodes were identified as the major stimulators of CD4 T cell activation. Finally, the migration and maturation of mucosal DC was independent of direct signaling, highlighting the contribution of epithelial factors in the mucosal adjuvant effect of flagellin. In conclusion, these data demonstrate that adjuvant activity can be dissociated from inflammatory cell recruitment an open new perpectives for improvement of vaccines. Female C57BL/6J (6 weeks old) mice were immunized with the TLR5 agonist Flagellin (1μg diluted in PBS) by intranasal (i.n.) administration. Blood samples of four time points post immunization were taken at 2h, 4h, 18h and 48h. Microarray experiments were performed as single-color hybridizations.
2014-01-01 | E-GEOD-46421 | biostudies-arrayexpress
Project description:For atypical meningiomas (AM), the combination of gross total resection (GTR) and adjuvant radiotherapy (ART) is still a controversial therapeutic strategy to improve prognosis. This study analysed the factors influencing the prognosis on AM patients treated with GTR+ART by investigating both clinical characteristics and the change in microRNA (miRNA) expression.Adult AM patients who were admitted to the Tiantan hospital from 2008 to 2015 and underwent GTR+ART were included. Patients who suffered recurrence within 3 years after operation were considered radioresistant, while the others were considered radiosensitive. Clinical characterizations were compared between these two groups. The miRNAs expression was detected via miRNA microarray in 10 patients, 5 from the radiosensitive group and 5 from the radioresistant group.No significant difference was found in the clinical characteristics. between radiosensitive and radioresistant patients. We found 7 significantly upregulated miRNAs and 7 significantly downregulated miRNAs in patients resistant to radiotherapy. The differentially expressed miRNAs were enriched mostly in the Fatty acid metabolic pathways (hsa00061, hsa01212) and TGF-β signalling pathway (hsa04350). For AM patients treated with GTR+ART, the changes in miRNA expression discovered in this study may be a potential predictor of individual sensitivity to adjuvant radiotherapy. Further research is needed regarding the predictive power and mechanism by which these miRNAs influence prognosis.
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Project description:The activity of the potent nasal adjuvant flagellin depends on initial activation of airway epithelilal cells. This study aims at investigating the immune cells involved in the antigen presentation within the respiratory tract. First, microarrays characterized that activation/recruitment of immune cells was the main signature of flagellin activation in lung. Neutrophils and classical monocytes were strongly recruited into the lungs and take up antigen upon nasal administration of flagellin. In contrast, the numbers of lung CD11b+ or CD103+ DC and alveolar macrophages were not enhanced although these cells were very efficient in antigen uptake. Our experiments showed that CD11b+ DC but not monocytes, PMN, CD103+ DC are not essential for the adjuvant effect. Flagellin signaling enhanced the functional activation of lung CD11b+ conventional DC and their migration to the lymph nodes. Using Cd11c-DTR mice, CD11b+ DC from lymph nodes were identified as the major stimulators of CD4 T cell activation. Finally, the migration and maturation of mucosal DC was independent of direct signaling, highlighting the contribution of epithelial factors in the mucosal adjuvant effect of flagellin. In conclusion, these data demonstrate that adjuvant activity can be dissociated from inflammatory cell recruitment an open new perpectives for improvement of vaccines.
2014-01-01 | GSE46421 | GEO
Project description:Background: Estrogen receptor positive (ER+) breast cancers (BC) are heterogeneous with regard to their clinical behavior and response to therapies. The ER is currently the best predictor of response to the anti-estrogen agent tamoxifen, yet up to 30-40% of ER+BC will relapse despite tamoxifen treatment. New prognostic biomarkers and further biological understanding of tamoxifen resistance are required. We used gene expression profiling to develop an outcome-based predictor using a training set of 255 ER+ BC samples from women treated with adjuvant tamoxifen monotherapy. We used clusters of highly correlated genes to develop our predictor to facilitate both signature stability and biological interpretation. Independent validation was performed using 362 tamoxifen-treated ER+ BC samples obtained from multiple institutions and treated with tamoxifen only in the adjuvant and metastatic settings. Results: We developed a gene classifier consisting of 181 genes belonging to 13 biological clusters. In the independent set of adjuvantly-treated samples, it was able to define two distinct prognostic groups (HR 2.01 95%CI: 1.29-3.13; p=0.002). Six of the 13 gene clusters represented pathways involved in cell cycle and proliferation. In 112 metastatic breast cancer patients treated with tamoxifen, one of the classifier components suggesting a cellular inflammatory mechanism was significantly predictive of response. Conclusions: We have developed a gene classifier that can predict clinical outcome in tamoxifen-treated ER+ BC patients. Whilst our study emphasizes the important role of proliferation genes in prognosis, our approach proposes other genes and pathways that may elucidate further mechanisms that influence clinical outcome and prediction of response to tamoxifen. Experiment Overall Design: dataset of microarray experiments from primary breast tumors of patients treated by Tamoxifen in adjuvant setting. No replicate, no reference sample.
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