TTF1 and TKTL1 mRNAs in Extracellular Vesicles as a Blood Biomarker for Lung Adenocarcinoma

Lung cancer remains the greatest cause of cancer related deaths and Low Dosage Computerized Tomography (LDCT) has been shown to improve early detection of lung cancer and survival rate of high risk individuals. However, such imaging is limited by high rates of false positivity leading to unnecessary patient anxiety and invasive procedures. Complementary blood biomarkers could increase the accuracy of early detection. We conducted next generation sequencing on extracellular vesicles (EVs) in plasma in cohorts of smoking and age matched individuals with surgically documented solitary lung nodules that were either adenocarcinomas or benign granulomas, and identified a glucose regulation gene TKTL1 as the most upregulated mRNA between the two cohorts. Together with a previously identified gene, TTF1, we designed molecular beacons and used a novel and yet facile tethered lipoplex nanoparticle (TLN) nanochip to assess their performance in lung cancer detection. Overall design: Three separate compartments of plasma (whole plasma, EV and EV-free plasma) from a small number of malignant intermediate pulmonary nodules (IPN) patients with benign (N=10) or malignant Stage IA/B IPNs (N=7)