THE PLURIPOTENCY FACTORS’ DETERMINATION OF THE TKIS OUTCOMES IN LUNG ADENOCARCINOMA WAS DEPENDENT ON THE LOAD OF THE SPECIAL-THREE MUSKETEERS

Abstract

TYPE: Abstract TOPIC: Lung Cancer PURPOSE: Patients bearing different E/K/P mutations could be defined and grouped with sensitive or resistant response by their signatures, and gene mutation load of EGFR, KRAS and TP53 (E/K/P) based pluripotency predicators will help to determine the most effective treating strategy of using targeted or chemo-radio therapeutic agents alternatively METHODS: Pan-Lung data acquiring and analyzing，Survival analysis，Cells culturing and Erlotinib resistant cells establishment .Stem-like cells isolation and functional identification,Quantitative real-time PCR and western blot,Statistical analysis RESULTS: The heterogenic signatures of Erlotinib resistant lung adenocarcinoma cells，KRAS activation of the pluripotency factors contributed to the stem cells’ renewal ability， Cancer stem-like cells are resistant to TKIs treatments.EGFR status association with KRAS and TP53 mutations indicated poorer living expectation,Smoking signatures indicated a cluster of mutated genes,Malignant activation was equal between men and women bearing mutated EGFR, KRAS and TP53,Stemness associates helped to distinguish that whose survival expectance will benefit from TKIs treatment CONCLUSIONS: smoking history and status were the independent risk factors that associated with higher mutant burden in lung adenocarcinoma patients, and smoking alone probably resulted in poorer TKIs treatment response in patients bearing EGFR, TP53 and KRAS mutations. CLINICAL IMPLICATIONS: In lung adenocarcinoma patients bearing EGFR mutation, smoking status tended to be a good predicator of TKIs therapy response, especially in female patients DISCLOSURE: This experiment was supported by National Science Foundation for Young Scientists of China, grant No. 81602597 (Referred to Xin Sun). Foundation Research Project of Shaanxi Province, 2021SF-117 (Referred to Xin Sun). The Natural Science Basic Research Pro KEYWORD: Non-small cell lung cancer