Font Size: a A A

Antibody Microarray Technology And Its Applications In Hepatocellular Carcinoma And Psoriasis Biomarker Studies

Posted on:2020-05-03Degree:MasterType:Thesis
Country:ChinaCandidate:M XuFull Text:PDF
GTID:2381330575958255Subject:Analytical Chemistry
Abstract/Summary:PDF Full Text Request
One of the key points of early diagnosis and effective treatment of diseases is to find biomarker molecules about the disease's occurrence and development.The method to discover valuable biomarkers is an important cornerstone of the development of precision medicine.Serum and plasma contain abundant biological information that reflect the body's physiological and pathological conditions and is therefore a valuable sample type for disease biomarkers.Antibody microarray is high throughput and sensitivity,so it is suitable for detecting low abundance proteins in serum and plasma.Data-independent acquisition mass spectrometry(DIA-MS)is high coverage for the detection of serum and plasma proteome.In this paper,we first used antibody microarray to detect the serum of liver disease patients,and initially find out potential biomarkers of liver cancer.Then we established an in-depth serum proteomics platform by combining antibody microarray and DIA-MS allowing the exploration of protein changes during psoriasis and their relationship to clinical data.And the detail was as follows:1.We detected the protein expression profile and identified the potential biomarkers of liver disease serum based on antibody microarray.First of all,we used a commercial antibody microarray composed of 1000 serum protein antibodies to detect hepatitis,cirrhosis,and Hepatocellular Carcinoma(AFP-)samples by biotin-labeling of the serum proteins,as well as the healthy control.Then,the differentially expressed proteins were identified by one-way ANOVA with a p value of 0.01 and multiple verified by custom microarray fabricated in laboratories.Indicating the antibody microarray can detect the serum protein expression profiles with good repeatability and specificity.Four potential biomarkers(AFP,CA125,MINA,D-Dimer)were confirmed using custom antibody arrays,in which MINA and D-Dimer were closely related to cirrhosis and Hepatocellular Carcinoma,respectively.Therefore,MINA and D-Dimer hold potential value in the prognosis in liver cancer.In Conclusion,The antibody microarray method can be used to screen the liver cancer serum markers with great clinical diagnosis significance,which lays a foundation for further clinical verification.2.We developed a novel in-depth serum proteomics platform capable of analyzing the serum proteome across 10 orders or magnitude by combining data obtained from DIA-MS and customizable antibody microarrays.Using psoriasis as a proof-of-concept disease model,we screened 50 serum proteomes from healthy controls and psoriasis patients before and after treatment with traditional Chinese medicine(YinXieLing)on our in-depth serum proteomics platform.We identified 106 differentially-expressed proteins in psoriasis patients involved in psoriasis-relevant biological processes,such as blood coagulation,inflammation,apoptosis and angiogenesis signaling pathways.In addition,unbiased clustering and principle component analysis revealed 58 proteins discriminating healthy volunteers from psoriasis patients and 12 proteins distinguishing responders from non-responders to YinXieLing.To further demonstrate the clinical utility of our platform,we performed correlation analyses between serum proteomes and psoriasis activity and found a positive association between the psoriasis area and severity index(PASI)score with three serum proteins(PI3,CCL22,IL12B).In Conclusion,Taken together,these results demonstrate the clinical utility of our in-depth serum proteomics platform to identify specific diagnostic and predictive biomarkers of psoriasis and other diseases.
Keywords/Search Tags:Hepatocellular carcinoma, Protein expression profile, Proteomics, Data-Independent acquisition Mass spectrometry, Antibody microarray, Biomarker, Psoriasis
PDF Full Text Request
Related items