| Objective:Lung cancer is the most common malignant tumor with the highest mortality in the world.The survival time of advanced non-small cell lung cancer is short and the course of disease progresses rapidly.Traditional treatment methods cannot improve the survival time of advanced patients.In recent years,the mutation of anaplastic lymphoma kinase(ALK)gene in advanced non-small cell lung cancer has become one of the key points in the era of individualized treatment,including point mutation,gene fusion and gene amplification.ALK gene fusion is sensitive to targeted drugs,and the most common subtype of ALK gene fusion is EML4-ALK gene fusion.EML4-ALK gene has low fusion rate,few clinical cases,lack of uniqueness and low late survival rate.With the development of bioinformatics,targeted drugs developed for ALK gene fusion can improve the survival rate of patients with advanced non-small cell lung cancer and prolong their progression-free survival.However,acquired drug resistance appears in the clinical application process,which increases the difficulty of patients’ treatment.The purpose of this paper is to analyze the relationship between the fusion state of EML4-ALK gene and the clinicopathological features of non-small cell lung cancer,analyze the clinicopathological features of EML4-ALK gene fusion subgroup of non-small cell lung cancer and the factors affecting the prognosis,and further analyze the drug resistance genes of targeted drugs through the biological information analysis technology,so as to provide help for pathological diagnosis,clinical treatment and exploration of the molecular mechanism of drug resistance in non-small cell lung cancer.Methods:1.This study was approved by the Ethics Committee.A total of 1422 cases of lung cancer were collected from 2018 to 2021,which were detected by EML4-ALK gene in hospital pathology department.Among them,there were 77 cases with EML4-ALK gene fusion and 1345 cases without fusion.The relationship between the fusion status of EML4-ALK gene and the general clinical data,histological morphology,pathological diagnosis and prognosis of non-small cell lung cancer was statistically analyzed.The relationship between clinicopathological features and prognosis,the use of targeted drugs and drug resistance in EML4-ALK gene fusion non-small cell lung cancer were statistically analyzed,and the survival analysis was carried out.2.In this study,GSE73167 gene chip with targeted drug resistance was downloaded through GEO platform,and the differential genes in Alectinib-resistant transcripts were screened by R language according to the standard of | logFC |>1 and adj P<0.01.The up-regulated genes and down-regulated genes were enriched and analyzed by DAVID database respectively.Results:1.Among 1422 cases of non-small cell lung cancer,77 cases(5.4%)were fused with EML4-ALK gene,and 1345 cases(94.6%)were not fused with EML4-ALK gene,including 1404 cases of adenocarcinoma and 18 cases of non-adenocarcinoma(13 cases of squamous cell carcinoma,2 cases of mucoepidermoid carcinoma and 1 case of large cell neuroendocrine carcinoma).Among 77 cases of EML4-ALK gene fusion(5.4%),76 cases were adenocarcinoma and 1 case was mucoepidermoid carcinoma.The follow-up time was 12 months to 48 months.Through statistical analysis,it is concluded that the fusion rate of ALK gene with age ≤57(7.3%)is higher than that with age>57(3.8%);The fusion rate of ALK gene was higher in cases with tumor nodules larger than 3 cm(11.1%)than<3 cm(5.3%).Pathological types showed that the fusion rate of ALK gene in invasive adenocarcinoma(5.6%)was higher than that in non-adenocarcinoma(5.4%)and invasive mucinous adenocarcinoma(47.8%)was higher than that in invasive adenocarcinoma(4.7%).The fusion rate of ALK gene in cases with lymph node metastasis(21.7%)was higher than that in cases without lymph node metastasis(3.3%).The fusion rate of ALK gene in patients with distant metastasis(17.1%)was higher than that in patients without distant metastasis(4.5%).TNM staging showed that the fusion rate of ALK gene in stage Ⅲ-Ⅳ(26.4)was higher than that in stage Ⅰ-Ⅱ(3.5%)(P<0.05).2.The survival time of patients with EML4-ALK gene fusion was significantly shorter than that of patients without EML4-ALK gene fusion.3.The survival time of patients with drug resistance to targeted drugs is shorter than that of patients without drug resistance.4.GSE73167 chip contains 34,183 transcripts,covering 21,755 human gene names.According to the standard of | logfc |>1 and adjP<0.01,359 differentially expressed genes of targeted drug resistance in non-small cell lung cancer were screened by R language,including 129 up-regulated genes and 230 down-regulated genes.5.According to the stDAVIDard of P<0.05,129 up-regulated genes were significantly enriched in Wnt signaling pathway,Hippo signaling pathway and basal cell carcinoma by KEGG.GO enrichment of 129 up-regulated genes was not significant(P>0.05).230 down-regulated genes were significantly enriched by KEGG,including rheumatoid arthritis,asthma,influenza A,allograft rejection,antigen processing and presentation.230 down-regulated genes were significantly enriched by GO,including peptide crosslinking,keratinocyte differentiation,keratinocyte envelope,structural molecular activity,MHC Ⅱ receptor activity,peptide antigen binding,protease binding and tumor necrosis factor-activated receptor activity.Conclusion:1.The fusion rate of ALK gene was high in cases with age<57 years,tumor nodule>3cm,lymph node metastasis and distant metastasis(P<0.05);In the case of ALK gene fusion,the histological types of patients’ specimens showed that the ALK gene fusion rate of invasive mucinous adenocarcinoma was higher than that of invasive adenocarcinoma(P<0.05).There is no significant correlation between gender and lymph node metastasis and the survival time of patients.2.The prognosis of non-small cell patients with 2.EML4-ALK gene fusion is poor.3.The survival rate of patients with non-small cell lung cancer after targeted drug resistance is low.4.GSE73167 chip contains 359 differentially expressed genes of drug resistance in non-small cell lung cancer,including 129 up-regulated genes and 230 down-regulated genes.5.129 up-regulated genes were significantly enriched in two pathways and one disease,while 129 up-regulated genes were not significantly enriched(P>0.05).230 down-regulated genes were significantly enriched in 14 diseases and 6 metabolic and biochemical processes by KEGG,and in 9 biological processes,8 cellular components and 5 molecular functions by GO. |
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