Serum Type XIX Collagen is Significantly Elevated in Non-Small Cell Lung Cancer: A Preliminary Study on Biomarker Potential
Type XIX collagen is a poorly characterized collagen associated with the basement membrane. It is abnormally regulated during breast cancer progression and the NC1 (XIX) domain has anti-tumorigenic signaling properties. However, little is known about the biomarker potential of collagen XIX in cancer...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/6/1510 |
| _version_ | 1797565739197005824 |
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| author | Jeppe Thorlacius-Ussing Tina Manon-Jensen Shu Sun Diana J. Leeming Jannie M. Sand Morten Karsdal Nicholas Willumsen |
| author_facet | Jeppe Thorlacius-Ussing Tina Manon-Jensen Shu Sun Diana J. Leeming Jannie M. Sand Morten Karsdal Nicholas Willumsen |
| author_sort | Jeppe Thorlacius-Ussing |
| collection | DOAJ |
| description | Type XIX collagen is a poorly characterized collagen associated with the basement membrane. It is abnormally regulated during breast cancer progression and the NC1 (XIX) domain has anti-tumorigenic signaling properties. However, little is known about the biomarker potential of collagen XIX in cancer. In this study, we describe a competitive ELISA, named PRO-C19, targeting the C-terminus of collagen XIX using a monoclonal antibody. PRO-C19 was measured in serum of patients with a range of cancer types and was elevated in non-small cell lung cancer (NSCLC) (<i>p</i> < 0.0001), small cell lung cancer (<i>p</i> = 0.0081), breast (<i>p</i> = 0.0005) and ovarian cancer (<i>p</i> < 0.0001) compared to healthy controls. In a separate NSCLC cohort, PRO-C19 was elevated compared to controls when evaluating adenocarcinoma (AD) (<i>p</i> = 0.0003) and squamous cell carcinoma (SCC) (<i>p</i> < 0.0001) patients but was not elevated in chronic obstructive pulmonary disease patients. SCC also had higher PRO-C19 levels than AD (<i>p</i> = 0.0457). PRO-C19 could discriminate between NSCLC and healthy controls (AUROC:0.749 and 0.826 for AD and SCC, respectively) and maintained discriminatory performance in patients of tumor stages I+II (AUROC:0.733 and 0.818 for AD and SCC, respectively). Lastly, we confirmed the elevated type XIX collagen levels using gene expression data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) initiatives. In conclusion, type XIX collagen is released into circulation and is significantly elevated in the serum of cancer patients and PRO-C19 shows promise as a cancer biomarker. |
| first_indexed | 2024-03-10T19:17:19Z |
| format | Article |
| id | doaj.art-c9c6860f2efe43299845ab62ff958007 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T19:17:19Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c9c6860f2efe43299845ab62ff9580072023-11-20T03:20:55ZengMDPI AGCancers2072-66942020-06-01126151010.3390/cancers12061510Serum Type XIX Collagen is Significantly Elevated in Non-Small Cell Lung Cancer: A Preliminary Study on Biomarker PotentialJeppe Thorlacius-Ussing0Tina Manon-Jensen1Shu Sun2Diana J. Leeming3Jannie M. Sand4Morten Karsdal5Nicholas Willumsen6Biomarkers and Research, Nordic Bioscience A/S, 2730 Herlev, DenmarkBiomarkers and Research, Nordic Bioscience A/S, 2730 Herlev, DenmarkBiomarkers and Research, Nordic Bioscience A/S, 2730 Herlev, DenmarkBiomarkers and Research, Nordic Bioscience A/S, 2730 Herlev, DenmarkBiomarkers and Research, Nordic Bioscience A/S, 2730 Herlev, DenmarkBiomarkers and Research, Nordic Bioscience A/S, 2730 Herlev, DenmarkBiomarkers and Research, Nordic Bioscience A/S, 2730 Herlev, DenmarkType XIX collagen is a poorly characterized collagen associated with the basement membrane. It is abnormally regulated during breast cancer progression and the NC1 (XIX) domain has anti-tumorigenic signaling properties. However, little is known about the biomarker potential of collagen XIX in cancer. In this study, we describe a competitive ELISA, named PRO-C19, targeting the C-terminus of collagen XIX using a monoclonal antibody. PRO-C19 was measured in serum of patients with a range of cancer types and was elevated in non-small cell lung cancer (NSCLC) (<i>p</i> < 0.0001), small cell lung cancer (<i>p</i> = 0.0081), breast (<i>p</i> = 0.0005) and ovarian cancer (<i>p</i> < 0.0001) compared to healthy controls. In a separate NSCLC cohort, PRO-C19 was elevated compared to controls when evaluating adenocarcinoma (AD) (<i>p</i> = 0.0003) and squamous cell carcinoma (SCC) (<i>p</i> < 0.0001) patients but was not elevated in chronic obstructive pulmonary disease patients. SCC also had higher PRO-C19 levels than AD (<i>p</i> = 0.0457). PRO-C19 could discriminate between NSCLC and healthy controls (AUROC:0.749 and 0.826 for AD and SCC, respectively) and maintained discriminatory performance in patients of tumor stages I+II (AUROC:0.733 and 0.818 for AD and SCC, respectively). Lastly, we confirmed the elevated type XIX collagen levels using gene expression data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) initiatives. In conclusion, type XIX collagen is released into circulation and is significantly elevated in the serum of cancer patients and PRO-C19 shows promise as a cancer biomarker.https://www.mdpi.com/2072-6694/12/6/1510collagen XIXECMbiomarkerserumcancerNSCLC |
| spellingShingle | Jeppe Thorlacius-Ussing Tina Manon-Jensen Shu Sun Diana J. Leeming Jannie M. Sand Morten Karsdal Nicholas Willumsen Serum Type XIX Collagen is Significantly Elevated in Non-Small Cell Lung Cancer: A Preliminary Study on Biomarker Potential Cancers collagen XIX ECM biomarker serum cancer NSCLC |
| title | Serum Type XIX Collagen is Significantly Elevated in Non-Small Cell Lung Cancer: A Preliminary Study on Biomarker Potential |
| title_full | Serum Type XIX Collagen is Significantly Elevated in Non-Small Cell Lung Cancer: A Preliminary Study on Biomarker Potential |
| title_fullStr | Serum Type XIX Collagen is Significantly Elevated in Non-Small Cell Lung Cancer: A Preliminary Study on Biomarker Potential |
| title_full_unstemmed | Serum Type XIX Collagen is Significantly Elevated in Non-Small Cell Lung Cancer: A Preliminary Study on Biomarker Potential |
| title_short | Serum Type XIX Collagen is Significantly Elevated in Non-Small Cell Lung Cancer: A Preliminary Study on Biomarker Potential |
| title_sort | serum type xix collagen is significantly elevated in non small cell lung cancer a preliminary study on biomarker potential |
| topic | collagen XIX ECM biomarker serum cancer NSCLC |
| url | https://www.mdpi.com/2072-6694/12/6/1510 |
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