The Study Of Differentially Expressed And Survival-related Proteins In Lung Adenocarcinoma With Bone Metastasis

Background Despite recent advances in targeted and immune-based therapies,the poor prognosis of lung adenocarcinoma(LUAD) with bone metastasis(BM) remains a challenge.Methods First,two-dimensional gel electrophoresis(2-DE) was used to identify proteins that were differentially expressed in LUAD with BM.Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry(MALDI-TOF-MS) was used to identify these proteins.The Cancer Genome Atlas(TCGA) was used to identify mutations in these differentially expressed proteins and Kaplan Meier plotter(KM Plotter) was used to generate survival curves for the analyzed cases.Second,Immunohistochemistry(IHC) and Western blot were used to check the expression of proteins in 28 BM patients and 9 LUAD patients.And do patient' follow-up.Results We identified a number of matched proteins from 2-DE.Low expression of Aldehyde dehydrogenase-2(ALDH2),high expression of Enolase1(ENO1)(HR=1.67,logrankP=1.9E-05),Ribosomal protein lateral stalk subunit P2(RPLP2)(HR=1.77,logrankP=2.9E-06),and NME/NM23 Nucleoside Diphosphate Kinase 2(NME1-NME2)(HR=2.65,logrankP=3.9E-15)were all significantly associated with poor survival(p<0.05).Further,ENO1 was up-regulated(p=0.0004).ALDH2(p=8.53E-11) and Calcyphosine(CAPS1)was down-regulated(p=5.34E-07) in TCGA LUAD RNA-seq expression data.IHC revealed that prominent ENO1 staining(OR=7.5,p=0.034),low levels of ALDH2(OR = 0.568,p=0.036) and CAPS1(OR=0.01,p<0.0001)were significantly associated with BM incidence.We also found that LUAD patients with low expression of ALDH2,high expression of ENO1 and RPLP2 had worse overall survival.Finally,we found that low expression of ALDH2 in lung cancer may occur DNA methylation,which inhibits cell proliferation,migration and Epithelial mesenchymal transformation(EMT).Conclusion This is the first instance where the genes ALDH2,ENO1,RPLP2,NME1-NME2 and CAPS1 were associated with disease severity and progression in LUAD patients with BM.Thus,with this study,we have identified potential biomarkers and therapeutic targets for this disease.