signing Six-gene predicts survival after targeted therapy for NSCLC -
By Sarah Pritchard, medwireNews Reporter
The presence of a six-gene profile microRNAs in patients with lung cancer non-small advanced squamous cell (NSCLC) predicts reduced survival probability after first-line treatment with targeted therapy followed by chemotherapy for the disease progression, the results indicate research.
Although the results "should be further validated," the researchers believe that their analysis "supports the hypothesis that circulating [microRNA's] can be further developed as predictive markers for treatment of targeted EGFR "in a population of NSCLC whose response to epidermal receptor epidermal growth factor (EGFR) tyrosine kinase inhibitors is unknown.
Using 49 participants of phase II SAKK (clinical research Swiss Group cancer) 19/05 trial, the Swiss research team analyzed samples of pretreatment blood, and taken 24 hours after the start of bevacizumab or erlotinib to identify microRNA prognostic of overall survival.
patients received bevacizumab 15 mg / kg on the first day of each 3-week cycle and simultaneous erlotinib 150 mg / day until disease progression or intolerable toxicity, and survived a median of 16.1 months.
expression profiling is identified in the peripheral blood of patients of 424 microRNAs revealed 10 that were significantly associated with overall survival. The strongest prognostic marker was hsa-miR-29a, with a hazard ratio of 6.44, says Markus Joerger, of the Cantonal Hospital of St. Gallen, and colleagues Lung cancer . Indeed, many fewer patients with high levels of expression of this microRNA were alive after 10 months compared to their counterparts who had low expression at 54% against 83%
Six microRNAs of -. Hsa-mirn-29a, miR-542-5p HSA, hsa-miR-502-3p, hsa-miR-376a, hsa-miR-500a, hsa-miR-424 - had the most robust association with survival after resampling precision analysis, giving a chance to 44% reduced survival for patients with this genetic signature. The cumulative survival rate for those with high versus low risk signatures were about 29 months compared to over 45 months.
Further analysis indicated 12 microRNAs that were significantly associated with the percentage of tumor shrinkage after treatment. In particular, has-miR-665, which at high expression levels increased significantly the chances of getting a removal of the tumor patients.
"molecular sub-classification of NSCLC is essential to improve clinical outcomes, but there are several drawbacks, including small amounts or poor quality diagnostic tissue tumor heterogeneity genetic tumor in space and time, and the risk and unwillingness to do repeated biopsies in patients with incurable tumors, "write Joerger et al.
"Therefore, circulating biomarkers are an interesting alternative to derived tumor biomarkers," they conclude.
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