Correlation Between D-dimer And Fibrinogen Levels And Crizotinib Efficacy

Background and purpose: Lung cancer is not only the bulk ordinary malignant tumor in China,but also the most lethal malignant tumor.Its 5-year survival rate is only4%～17%,of which lung adenocarcinoma(LUAD)accounts for the highest proportion.Anaplastic lymphoma kinase(ALK)is used as a molecular target of LUAD,and ALK gene rearrangement accounts for 3%～5% in non-small cell lung cancer(NSCLC).Crizotinib,as a first-generation ALK inhibitor,is one of the preferred regimens for ALK-positive NSCLC,which can inhibit tumor progression by inhibiting ALK.In view of the fact that crizotinib is resistant in most patients in the process of guiding clinical use,this study intends to find clinically convenient detection indicators to predict the drug effect of crizotinib in ALK-positive patients.Methods: This study properly and logically collected total number 122 patients with ALK-positive lung cancer who received crizotinib from July 2014 to July 2020 with complete clinical data.(1)Download transcriptome data and clinical information numbered GSE125864 from GEO database,and use R software(version 3.63)to preprocess the gene probe,name,expression amount of transcriptome data between primary and metastases before and after crizotinib resistance in patients with ALKpositive lung adenocarcinoma in GEO database for subsequent analysis;(2)Collect clinical information and peripheral blood parameters of patients with positive ALK fusion gene detected by Fluorescence in Situ hybridization(FISH)or Ventana immunohistochemistry(IHC);(3)Analysis of differential genes and pathways in ALKpositive patients receiving crizotinib by bioinformatics technology;(4)To analyze the predictive value of D-dimer and FIB levels in peripheral blood before receiving crizotinib treatment in patients with crizotinib lung cancer.Results: Differential gene analysis showed that FGA and FGG genes encoding fibrinogen were highly expressed in the metastatic group compared with the primary lesion group,and the enrichment analysis of Kyoto gene and genome encyclopedia pathway showed that the differential genes were mainly concentrated in complement and coagulation cascade pathways.High expression of core genes FGA and FGG in lung cancer predicted poor overall survival(P=0.0096,P=0.014).Clinical data analysis showed that patients with abnormal levels of FIB and D-dimer before taking crizotinib had significantly lower progression-free survival(PFS)than normal patients(P<0.05,P<0.001),and FIB and D-dimer in peripheral blood before treatment had a good predictive effect on PFS(AUC=0.798;AUC=0.906),the critical cut-off value for FIB was 3.165(sensitivity 88.2%,specificity 63%),and the critical cut-off value for Ddimer was 0.655(sensitivity 81.6%,specificity 84.8%).Univariate and multivariate cox regression analysis showed FIB(HR,1.165;95% CI: 1.028-1.321)(P=0.017)and Ddimer(HR,1.185;95% CI: 1.098-1.278)(P<0.001)can be used as an independent predictor for evaluating PFS.Conclusion: Bioinformatics analysis showed that FGA and FGG,the core genes encoding FIB,were expressed at high levels in liver metastases,and were closely associated with poor outcomes in lung cancer patients in database survival analysis.The level of FIB and D-dimer in peripheral blood before treatment has certain predictive value for the efficacy of ALK-positive crizotinib patients,or may provide new reference guidance for the clinical use of crizotinib.