Serum type xix collagen is significantly elevated in non-small cell lung cancer: A preliminary study on biomarker potential
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Serum type xix collagen is significantly elevated in non-small cell lung cancer : A preliminary study on biomarker potential. / Thorlacius-Ussing, Jeppe; Manon-Jensen, Tina; Sun, Shu; Leeming, Diana J.; Sand, Jannie M.; Karsdal, Morten; Willumsen, Nicholas.
In: Cancers, Vol. 12, No. 6, 1510, 2020, p. 1-14.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Serum type xix collagen is significantly elevated in non-small cell lung cancer
T2 - A preliminary study on biomarker potential
AU - Thorlacius-Ussing, Jeppe
AU - Manon-Jensen, Tina
AU - Sun, Shu
AU - Leeming, Diana J.
AU - Sand, Jannie M.
AU - Karsdal, Morten
AU - Willumsen, Nicholas
PY - 2020
Y1 - 2020
N2 - 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) (p < 0.0001), small cell lung cancer (p = 0.0081), breast (p = 0.0005) and ovarian cancer (p < 0.0001) compared to healthy controls. In a separate NSCLC cohort, PRO-C19 was elevated compared to controls when evaluating adenocarcinoma (AD) (p = 0.0003) and squamous cell carcinoma (SCC) (p < 0.0001) patients but was not elevated in chronic obstructive pulmonary disease patients. SCC also had higher PRO-C19 levels than AD (p = 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.
AB - 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) (p < 0.0001), small cell lung cancer (p = 0.0081), breast (p = 0.0005) and ovarian cancer (p < 0.0001) compared to healthy controls. In a separate NSCLC cohort, PRO-C19 was elevated compared to controls when evaluating adenocarcinoma (AD) (p = 0.0003) and squamous cell carcinoma (SCC) (p < 0.0001) patients but was not elevated in chronic obstructive pulmonary disease patients. SCC also had higher PRO-C19 levels than AD (p = 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.
KW - AD
KW - Biomarker
KW - Cancer
KW - Collagen XIX
KW - ECM
KW - NSCLC
KW - SCC
KW - Serum
UR - http://www.scopus.com/inward/record.url?scp=85086335593&partnerID=8YFLogxK
U2 - 10.3390/cancers12061510
DO - 10.3390/cancers12061510
M3 - Journal article
C2 - 32527017
AN - SCOPUS:85086335593
VL - 12
SP - 1
EP - 14
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 6
M1 - 1510
ER -
ID: 246826454