Development of approach for exploration of autoantibody profiles in cancer patients and identification of autoantibody signature for diagnosis of gastric cancer
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Latvijas Universitāte
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eng
Abstract
ANOTĀCIJA. Autoantivielu profilu analīzes metodikas izstrāde un kuņģa
vēža diagnostikā nozīmīgu autoantivielu identificēšana
Šī darba mērķis bija izstrādāt fāgu displeja antigēnu mikročipu izgatavošanas un apstrādes
tehnoloģiju un mikročipa datu analīzes procedūras, un izmantot tās autoantivielu profilu izpētei
pacientiem ar kuņģa vēzi, kuņģa iekaisuma slimībām un veseliem indivīdiem, kā arī humorālo
imūno atbilžu noteikšanai pret spermas-asociētajiem antigēniem. Tika izstrādātas procedūras divupakāpju
mikročipa datu normalizēšanai, kas definē atskaites punktus un ranžē antigēnus, ļaujot
atšķirt serum-pozitīvu no serum-negatīva signāla, un veikt kvantitatīvas analīzes. Tika identificēts
45-autoantivielu profils, kas ļāva atšķirt kuņģa vēzi no veseliem donoriem ar 74.5% precizitāti
(AUC=0.79, 58% jutība un 91% specifiskums); kuņģa vēzi no peptiskās čūlas ar 73.0% precizitāti,
un kuņģa vēzi no gastrīta ar 63.5% precizitāti.
fāgu displeja antigēnu mikročips, kuņģa vēzis, autoantivielas
ANNOTATION. Development of approach for exploration of autoantibody profiles in cancer patients and identification of autoantibody signature for diagnosis of gastric cancer This thesis is focused on the development of technology for the production and processing of phage-displayed antigen microarrays and procedures for the data analysis, and their application for the exploration of autoantibody profiles in patients with gastric cancer, gastric inflammatory diseases and healthy individuals, and assessment of humoral immune response against spermassociated antigens. The procedures for two-step normalization of microarray data, defining cutoffs and ranking were elaborated and allowed to discriminate between sero-positive and sero-negative cases and to perform quantitative analysis. The identified 45- autoantibody signature discriminate between gastric cancer and healthy control sera with 74.5% accuracy, gastric cancer and peptic ulcer with 73.0% accuracy, and gastric cancer and gastritis with 63.5% accuracy. phage-displayed antigen microarrays, gastric cancer, autoantibody
ANNOTATION. Development of approach for exploration of autoantibody profiles in cancer patients and identification of autoantibody signature for diagnosis of gastric cancer This thesis is focused on the development of technology for the production and processing of phage-displayed antigen microarrays and procedures for the data analysis, and their application for the exploration of autoantibody profiles in patients with gastric cancer, gastric inflammatory diseases and healthy individuals, and assessment of humoral immune response against spermassociated antigens. The procedures for two-step normalization of microarray data, defining cutoffs and ranking were elaborated and allowed to discriminate between sero-positive and sero-negative cases and to perform quantitative analysis. The identified 45- autoantibody signature discriminate between gastric cancer and healthy control sera with 74.5% accuracy, gastric cancer and peptic ulcer with 73.0% accuracy, and gastric cancer and gastritis with 63.5% accuracy. phage-displayed antigen microarrays, gastric cancer, autoantibody