Ex vivo multiplex profiling of protein tyrosine kinase activities in early stages of human lung adenocarcinoma

摘要: Despite constant improvement in existing therapeutic efforts, the overall survival rate of lung cancer patients remains low. Enzyme activities may identify new therapeutically targetable biomarkers and overcome marked lack correlation between cellular abundance translated proteins corresponding mRNA expression levels. We analysed tyrosine kinase to classify adenocarcinoma (LuAdCa) resection specimens based on their underlying changes processes pathways that are agents or result from malignant transformation. characterised 71 same-patient pairs early-stage LuAdCa non-neoplastic specimen lysates presence absence a inhibitor. performed ex vivo multiplex phosphorylation assays using 144 selected microarrayed substrates. The obtained 76 phosphotyrosine signature peptides were subsequently terms follow-up treatments outcomes recorded patient files. For tumour, node, metastasis (TNM) stage 1 patients, we noticed larger inhibitor-induced decrease for long-term as opposed short-term disease survivors, which 26 significantly (p < 0.01, FDR 3%) more inhibited survivors. Using statistical class prediction analysis, 'prognostic-signature' long- versus survivors correctly predicted status 73% our patients. Our translational approach assist clinical management after surgical help direct an optimal treatment strategy.