A Sensitive NanoString-Based Assay to Score STK11 (LKB1) Pathway Disruption in Lung Adenocarcinoma.
A Sensitive NanoString-Based Assay to Score STK11 (LKB1) Pathway Disruption in Lung Adenocarcinoma.
复制标题
DOI：
10.1016/j.jtho.2016.02.009
复制
发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Cress WD
中科院分区：
文献类型：
--
作者：
Chen L;Engel BE;Welsh EA;Yoder SJ;Brantley SG;Chen DT;Beg AA;Cao C;Kaye FJ;Haura EB;Schabath MB;Cress WD
Serine/threonine kinase 11 (STK11), better known as LKB1, is a tumor-suppressor commonly mutated in lung adenocarcinoma (LUAD). Previous work has shown that mutational inactivation of the STK11 pathway may serve as a predictive biomarker for cancer treatments including phenformin and COX-2 inhibition. Although immunohistochemistry and diagnostic sequencing are employed to measure STK11 pathway disruption, there are serious limitations to these methods emphasizing the importance to validate a clinically useful assay. An initial STK11 mutation mRNA signature was generated using cell line data and refined using three large, independent patient databases. The signature was validated as a classifier using The Cancer Genome Anatomy Project (TCGA) LUAD cohort as well as a 442-patient LUAD cohort developed at Moffitt. Finally, the signature was adapted into a NanoString -based format and validated using RNA samples isolated from FFPE tissue blocks corresponding to a cohort of 150 LUAD patients. For comparison, STK11 immunochemistry was also performed. The STK11 signature was found to correlate with null mutations identified by exon sequencing in multiple cohorts using both microarray and NanoString formats. While there was a statistically significant correlation between reduced STK11 protein expression by IHC and mutation status, the NanoString-based assay showed superior overall performance with a −0.1588 improvement in area under the curve in receiver-operator characteristic curve analysis (p<0.012). The described NanoString-based STK11 assay is a sensitive biomarker to study emerging therapeutic modalities in clinical trials.
