A Predictive Value Study Of Different Signaling Pathways In Non-small Cell Lung Cancer

Introduction: Lung cancer is a molecularly heterogeneous disease and the leading cause of cancer death,whose diagnosis rate and mortality rate are at the forefront of all tumors.With the rapid development of precision medicine and DNA sequencing technology,the application of small-molecule tyrosine kinase inhibitors has brought unprecedented survival benefits to patients with NSCLC.However,many patients are prone to develop drug resistance for various reasons after using TKIs for some time.To solve this problem,combination therapy has become a new idea of NSCLC targeted therapy.However,due to the large number of mutant genes in NSCLC and the complex regulatory mechanism,we still need to have a deeper understanding of the characteristics of mutated genes in NSCLC patients.Previous NSCLC treatment methods usually are targeted therapy for a single mutated gene,which is prone to drug resistance and co-mutation of other genes,always bringing great trouble to clinical treatment.Objective: In order to solve the limitations of single-gene and comutation classification,this study analyzed the gene mutation characteristics of adenocarcinoma and squamous cell carcinoma in patients with non-small cell lung cancer,and guided clinical treatment and prognosis by signaling pathway classification,so as to benefit more patients.Methods:(1)Data acquisition and analysis of patients in Xiangya Hospital: A total of 432 NSCLC patients from Xiangya Hospital from January 2016 to December 2019 were enrolled,including 146 cases of lung squamous cell carcinoma and 286 cases of lung adenocarcinoma.Statistical analysis was conducted after genetic testing.(2)TCGA data acquisition and analysis: gene mutation data and clinical data were downloaded and integrated from TCGA.The mutation frequency,co-mutation characteristics,and signal pathways enriched by most mutated genes of each gene were analyzed and counted,and then compared and verified with local corresponding data to find the similarities and differences.(3)Enter the medical record system of Xiangya Hospital and record the clinical data of the corresponding patients.All patients were then followed up by telephone to obtain their survival status or date of death,with follow-up up to January 10,2021.Graph Pad Prism was used for survival analysis and visualization.The 54 genes included in this study were: EGFR,KRAS,NRAS,BRAF,ALK,ERBB2,ERBB3,ERBB4,MET,ROS1,RET,FGFR1,FGFR2,FGFR3,NTRK1,PDGFRA,KIT,FLT3,IGF1 R,MAP2K1,JAK2,NF1,PIK 3CA,PTEN,AKT1,TSC1,TSC2,MTOR,RICTOR,PIK3R1,STK11,CTNNB1,APC,RNF43,MDM2,TP53,ATM,CCND1,CCNE1,CDK4,CDK6,RB1,CDKN2 A,NFE2L2,KEAP1,FAT3,FAT1,NF2,KDM5 A,NOTCH1,NOTCH2,FBXW7,CREBBP,and SPEN.Results: After the analysis of xiangya Hospital patients and TCGA data,the following results were obtained:(1)TP53 gene had the highest mutation frequency in patients with NSCLC;Lung adenocarcinoma often had mutations of proto-oncogenes such as EGFR and KRAS,while lung squamous cell carcinoma mainly had mutations of tumor suppressor genes such as TP53 and CDKN2 A.(2)KRAS,BRAF and PIK3 CA genes had high frequency mutation sites,while STK11 and CDKN2 A genes had random and scattered mutation sites in patients with non-small cell lung cancer,and no mutation sites or protein regions with high mutation concentration have been found to date.(3)EGFR was often combined with common mutations of other genes,such as TP53,KRAS,PIK3 CA,RB1 and MET.TP53 and PIK3 CA genes often existed as co-mutations of other genes,especially in lung squamous cell carcinoma.(4)Mutation genes of NSCLC were mainly concentrated in RTK/RAS,PI3K/AKT,Cell Cycle,TP53 and other signaling pathways.(5)Among RTK/RAS,PI3K/AKT,TP53 and Cell Cycle signaling pathways,patients with RTK/RAS pathway mutation had the best survival prognosis,while patients with Cell Cycle pathway mutation had the worst survival prognosis.Conclusion:(1)Common gene mutations in NSCLC patients were mainly enriched in RTK/RAS,PI3K/AKT,TP53 and Cell Cycle pathways.(2)The enrichment of gene mutations in RTK/RAS,PI3K/AKT,TP53 and Cell Cycle pathways in NSCLC patients was significantly correlated with the OS and PFS of patients.