Epitomics: Analysis of Plasma C9 Epitope Heterogeneity in the Plasma of Lung Cancer Patients and Control Subjects
The human proteome is more complex than the genetic code predicts it to be. Epitomics, or protein epitome profiling, is a tool for understanding sub-protein level variation. With the ultimate goal to explore C9 proteoforms and their relevance to lung cancer, here we report plasma C9 epitope-associat...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/18/14359 |
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| author | Ilona Tornyi Jozsef Lazar Aladar Pettko-Szandtner Eva Hunyadi-Gulyas Laszlo Takacs |
| author_facet | Ilona Tornyi Jozsef Lazar Aladar Pettko-Szandtner Eva Hunyadi-Gulyas Laszlo Takacs |
| author_sort | Ilona Tornyi |
| collection | DOAJ |
| description | The human proteome is more complex than the genetic code predicts it to be. Epitomics, or protein epitome profiling, is a tool for understanding sub-protein level variation. With the ultimate goal to explore C9 proteoforms and their relevance to lung cancer, here we report plasma C9 epitope-associated molecular heterogeneity in plasma samples of lung cancer patients and control subjects. We show three C9 epitopes (BSI0449, BSI0581, BSI0639) with markedly different association with lung cancer (“unaltered”, “upregulated” and “downregulated”). In order to exclude confounding effects, we show first that the three epitope-defining mAbs recognize C9 in purified form and in the natural context, in the human plasma. Then, we present data demonstrating the lack of major epitope interdependence or overlap. The next experiments represent a quest toward the understanding of the molecular basis of apparent disparate association with lung cancer. Using immunochemistry, SDS PAGE and LC-MS/MS technologies, we demonstrate that epitope-specific immunoprecipitates of plasma C9 seem identical regarding peptide sequence. However, we found epitope-specific posttranslational modification and coprecipitated protein composition differences with respect to control and lung cancer plasma. Epitope profiling enabled the classification of hypothetical C9 proteoforms through differential association with lung cancer. |
| first_indexed | 2024-03-10T22:39:51Z |
| format | Article |
| id | doaj.art-fe2f3dd47ebe4f9c8a22ee9f3629a0db |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T22:39:51Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fe2f3dd47ebe4f9c8a22ee9f3629a0db2023-11-19T11:11:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124181435910.3390/ijms241814359Epitomics: Analysis of Plasma C9 Epitope Heterogeneity in the Plasma of Lung Cancer Patients and Control SubjectsIlona Tornyi0Jozsef Lazar1Aladar Pettko-Szandtner2Eva Hunyadi-Gulyas3Laszlo Takacs4Department of Human Genetics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryBiosystems Immunolab Zrt., 4025 Debrecen, HungaryProteomics Laboratory, Biological Research Center, 6726 Szeged, HungaryProteomics Laboratory, Biological Research Center, 6726 Szeged, HungaryDepartment of Human Genetics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryThe human proteome is more complex than the genetic code predicts it to be. Epitomics, or protein epitome profiling, is a tool for understanding sub-protein level variation. With the ultimate goal to explore C9 proteoforms and their relevance to lung cancer, here we report plasma C9 epitope-associated molecular heterogeneity in plasma samples of lung cancer patients and control subjects. We show three C9 epitopes (BSI0449, BSI0581, BSI0639) with markedly different association with lung cancer (“unaltered”, “upregulated” and “downregulated”). In order to exclude confounding effects, we show first that the three epitope-defining mAbs recognize C9 in purified form and in the natural context, in the human plasma. Then, we present data demonstrating the lack of major epitope interdependence or overlap. The next experiments represent a quest toward the understanding of the molecular basis of apparent disparate association with lung cancer. Using immunochemistry, SDS PAGE and LC-MS/MS technologies, we demonstrate that epitope-specific immunoprecipitates of plasma C9 seem identical regarding peptide sequence. However, we found epitope-specific posttranslational modification and coprecipitated protein composition differences with respect to control and lung cancer plasma. Epitope profiling enabled the classification of hypothetical C9 proteoforms through differential association with lung cancer.https://www.mdpi.com/1422-0067/24/18/14359epitomicscomplement C9epitope profilingepitope heterogeneityproteoformbiomarker |
| spellingShingle | Ilona Tornyi Jozsef Lazar Aladar Pettko-Szandtner Eva Hunyadi-Gulyas Laszlo Takacs Epitomics: Analysis of Plasma C9 Epitope Heterogeneity in the Plasma of Lung Cancer Patients and Control Subjects International Journal of Molecular Sciences epitomics complement C9 epitope profiling epitope heterogeneity proteoform biomarker |
| title | Epitomics: Analysis of Plasma C9 Epitope Heterogeneity in the Plasma of Lung Cancer Patients and Control Subjects |
| title_full | Epitomics: Analysis of Plasma C9 Epitope Heterogeneity in the Plasma of Lung Cancer Patients and Control Subjects |
| title_fullStr | Epitomics: Analysis of Plasma C9 Epitope Heterogeneity in the Plasma of Lung Cancer Patients and Control Subjects |
| title_full_unstemmed | Epitomics: Analysis of Plasma C9 Epitope Heterogeneity in the Plasma of Lung Cancer Patients and Control Subjects |
| title_short | Epitomics: Analysis of Plasma C9 Epitope Heterogeneity in the Plasma of Lung Cancer Patients and Control Subjects |
| title_sort | epitomics analysis of plasma c9 epitope heterogeneity in the plasma of lung cancer patients and control subjects |
| topic | epitomics complement C9 epitope profiling epitope heterogeneity proteoform biomarker |
| url | https://www.mdpi.com/1422-0067/24/18/14359 |
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