Construction Of Secondary Transcriptome Database Of EGFR And KRAS-driven Lung Adenocarcinoma

PurposeThis study aims to screen EGFR,KRAS mutant lung adenocarcinoma specific and shared key molecular markers by analyzing the specific and shared transcriptional regulatory networks of EGFR and KRAS mutant lung adenocarcinomas.To explore the mechanism of metastasis,recurrence,drug resistance and poor prognosis of EGFR and KRAS mutant lung adenocarcinoma,and provide theoretical basis for the optimization of existing clinical protocols for EGFR and KRAS mutant lung adenocarcinoma.MethodFirst,the EGFR,KRAS mutant lung adenocarcinoma gene chip and high-throughput sequencing data of GEO and TCGA database were used as research objects,and a secondary database was established according to the proposed standard.Then,using differential expression,functional enrichment analysis and network analysis,the transcriptional regulatory networks of EGFR and KRAS mutant lung adenocarcinomas were established,and the genes related to metastasis,recurrence and drug resistance were analyzed.Survival analysis was used to screen prognosis-related genes.Subsequently,the association analysis method was used to establish a common transcriptional regulatory network of EGFR and KRAS mutant lung adenocarcinoma,and analysis the common relationship and interaction between the two at the transcriptional level to screen the key genes.ResultIn this study,a transcriptome database of EGFR and KRAS mutant lung adenocarcinomas was established with 9 corresponding survival databases,including3 gene chip databases and 6 transcriptome databases,and a total of 1542 lung cancer patients were included.The transcriptional regulatory map and mRNA subnetwork of EGFR mutant lung adenocarcinoma were constructed and analyzed.A total of 492 key genes were found,including 323 mRNA,156 lncRNA and 13 miRNA.GOfunctional enrichment analysis shows that these genes have a wide range of functions,including immunity,energy metabolism,cell cycle,angiogenesis,etc.,and are closely related to cancer.Among them,16 genes were associated with poor prognosis of EGFR-mutant lung adenocarcinoma(4 mRNAs,1 miRNA,11 lncRNAs).All key genes involved 37 signaling pathways including immunity,infection,cardiac function,and cell proliferation and differentiation.The transcriptional regulation map and mRNA subnetwork of KRAS mutant lung adenocarcinoma were constructed and analyzed.A total of 549 key genes were found,including 407 mRNA,118 lncRNA and 24 miRNA.GO functional enrichment analysis showed that these genes have a wide range of functions,and have a large number of cancer-promoting functions such as immunity,energy metabolism,cell cycle,and angiogenesis.Among them,26 genes were associated with poor prognosis of KRAS mutant lung adenocarcinoma(5 mRNA,4 miRNA,17 lncRNA).All key genes involved 109 signaling pathways including immunity,infection,cardiac function,and cell proliferation and differentiation.The transcriptional regulatory map and mRNA subnetwork of EGFR and KRAS mutant lung adenocarcinoma were constructed,and 1313 consensus key genes were found,including 209 mRNAs,57 miRNAs,and 1047 lncRNAs.There were 85 GO enrichment results,suggesting that these genes are functional.There is similarity;in the action pathway of different types of RNA,30 co-regulatory pathways were found.ConclusionEGFR mutant lung adenocarcinoma,LDLR,NT5 E,SALL1,NRIP3 are associated with poor prognosis at the mRNA level.LCN2 and CD52 are protective genes for the prognosis of EGFR-mutant lung adenocarcinoma;non-coding RNA,hsa-mir-182,AP000553.1.AP002478.1,C5orf64,C10orf91,FNDC1-IT1,HOTAIR,HS6ST2-AS1,MALAT1,STEAP2-AS1,U52111.1,and AL391152.1 are associated with poor prognosis,which will be verified in the future by basic and clinical studies.KRAS mutant lung adenocarcinoma,TCN1,FABP4,VIPR1,FAM83 A,GPC3may be associated with poor prognosis at mRNA level.COL6A6,HES6,SOSTDC1,PCP4 may be protective genes for prognosis of KRAS mutant lung adenocarcinoma;non-coding RNA,Hsa-mir-31,hsa-mir-143,hsa-mir-182,hsa-mir-200 a,AC022148.1,AC061975.6,AL391152.1,AP000553.1,AP002478.1,C5orf64,C10orf91,DLEU7-AS1,FNDC1-IT1,HOTAIR,HS6ST2-AS1,LINC00163,LINC00221,LINC00518,MALAT1,STEAP2-AS1,U52111.1 may be associated with poor prognosis,and further validation is required in the future through basic and clinical studies.EGFR,KRAS mutant lung adenocarcinoma,at the mRNA level,IL-6,UBE2 C,AURKA may become a common basic therapeutic target;in the non-coding RNA has-mir-182,AL391152.1.AP000553.1,AP002478.1,C5orf64,C10orf91,FNDC1-IT1,HOTAIR,HS6ST2-AS1,MALAT1,STEAP2-AS1,U52111.1 may be related to the interaction of EGFR and KRAS mutations,and further validation is required in the future through basic and clinical studies.