The Primary Study of Biomarkers for the Early Detection and the Treatment Effects Prediction of Human NSCLC
|Keywords||MALDI-TOF-MS CYFRA21-1 human lung squamous carcinoma serum protein XRCC1 gene NSCLC radiotherapy chemotherapy respone rate|
Part 1 Mass spectrometry analysis of CYFRA21-1 negative human lung squamous serum proteinsObjective:To establish proteomic profiling using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and to seek biomarkers of CYFRA21-1 negative human lung squamous for early diagnosis.Methods:The serum samples of 80 CYFRA21-1 negative human lung squamous carcinoma patients and 80 normal control subjects were randomly divided into two groups to build up the group of establishing model and the group of verifying model.The serum samples of establishing model were analyzed by the technique of MALDI-TOF-MS and ClinProTools software to Screen the differential proteins and establish the diagnostic mode1. The differential proteins and the model were verified by the groups of verifying mode1.The interested proteins were identified.Results:The serum protein spectrums of the group of establishing model including CYFRA21-1 negative human lung squamous carcinoma patients and normal control subjects were compared and got 24 differential proteins.Among them,8 differential proteins were selected to establish the diagnostic model of CYFRA21-1 negative human lung squamous carcinoma,the m/z were 1604.73、2852.48、3884.93、4641.3、5863.23、6629.82、7764.02、9285.52 respectively.The sensitivity and specificity of the model was 87.5%、97.5% respectively.The up-regulated proteins were1604.73(m/z)、6629.82(m/z)、2852.48(m/z)、5863.23(m/z);The down-regulated protein was 9285.52(m/z)、4641.3(m/z)、7764.02(m/z)、3884.93 (m/z).Conclusion:The biological markers in the earlier period of CYFRA21-1 negative human lung squamous carcinoma can be detected by the technology of MALDI-TOF-MS and the software of ClinProTools .It can be a new,easy,convenient analyzing method and have a potential applying value in the early diagnosis and therapy of human lung squamous carcinoma.Part 2 The association between single nucleotide polymorphism in XRCC1 gene Codon399 and the short-term effect of NP chemotherapy regiment combined with radiotherapy in NSCLCObjective:To study the relationship between XRCC1 gene Codon399 polymorphisms and the short-term effect of NP chemotherapy regiment combined with radiotherapy in NSCLC.Methods:Phlebotomize 52 patients of NSCLC and extract genome DNA from whole blood cells. Then perform PCR, and amplify the PCR products by ligase detection reaction(LDR), put the LDR products on sequencer to carry out electrophoresis and finally get the genotypes of XRCC1. The distribution of genotypes of the SNPs among the sensitive and resistant groups was compared.Results:The response rate of therapy is 50.00%. No significant difference was observed in the frequency of XRCC1 gene Codon399 allele between the two groups (P>0.05). The response rates of therapy for XRCC1 Arg/Arg, Arg/Gln+Gln/Gln genotypes were 54.16%, and 46.42% respectively. There were no statistical significance in difference of valid response rate of therapy among these genotypes (P>0.05).Conclusion:There are no significant correlation between the respone rates to NP chemotherapy regiment combined with radiotherapy of NSCLC.