Untargeted longitudinal analysis of a wellness cohort identifies markers of metastatic cancer years prior to diagnosis.
Aged
Biomarkers, Tumor
/ blood
Breast Neoplasms
/ blood
Carcinoembryonic Antigen
/ blood
Carcinoma, Neuroendocrine
/ blood
Case-Control Studies
GPI-Linked Proteins
/ blood
Health Promotion
/ statistics & numerical data
Humans
Longitudinal Studies
Lung Neoplasms
/ blood
Male
Middle Aged
Neoplasm Proteins
/ blood
Neoplasms
/ blood
Pancreatic Neoplasms
/ blood
Prospective Studies
Thyroid Neoplasms
/ blood
Time Factors
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
01 10 2020
01 10 2020
Historique:
received:
12
12
2019
accepted:
16
09
2020
entrez:
2
10
2020
pubmed:
3
10
2020
medline:
5
1
2021
Statut:
epublish
Résumé
We analyzed 1196 proteins in longitudinal plasma samples from participants in a commercial wellness program, including samples collected pre-diagnosis from ten cancer patients and 69 controls. For three individuals ultimately diagnosed with metastatic breast, lung, or pancreatic cancer, CEACAM5 was a persistent longitudinal outlier as early as 26.5 months pre-diagnosis. CALCA, a biomarker for medullary thyroid cancer, was hypersecreted in metastatic pancreatic cancer at least 16.5 months pre-diagnosis. ERBB2 levels spiked in metastatic breast cancer between 10.0 and 4.0 months pre-diagnosis. Our results support the value of deep phenotyping seemingly healthy individuals in prospectively inferring disease transitions.
Identifiants
pubmed: 33004987
doi: 10.1038/s41598-020-73451-z
pii: 10.1038/s41598-020-73451-z
pmc: PMC7529776
doi:
Substances chimiques
Biomarkers, Tumor
0
CEACAM5 protein, human
0
Carcinoembryonic Antigen
0
GPI-Linked Proteins
0
Neoplasm Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
16275Subventions
Organisme : NIEHS NIH HHS
ID : P30 ES017885
Pays : United States
Organisme : NIH HHS
ID : P30ES017885-01A1
Pays : United States
Références
Flores, M., Glusman, G., Brogaard, K., Price, N. D. & Hood, L. P4 medicine: how systems medicine will transform the healthcare sector and society. Per Med 10, 565–576 (2013).
doi: 10.2217/pme.13.57
Cristofanilli, M. Circulating tumour cells: telling the truth about metastasis. Lancet Oncol. 15, 365–366 (2014).
doi: 10.1016/S1470-2045(14)70091-9
Schwarzenbach, H., Hoon, D. S. B. & Pantel, K. Cell-free nucleic acids as biomarkers in cancer patients. Nat. Rev. Cancer 11, 426–437 (2011).
doi: 10.1038/nrc3066
Wulfkuhle, J. D., Liotta, L. A. & Petricoin, E. F. Proteomic applications for the early detection of cancer. Nat. Rev. Cancer 3, 267–275 (2003).
doi: 10.1038/nrc1043
Cohen, J. D. et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science 359, 926–930 (2018).
doi: 10.1126/science.aar3247
Zubair, N. et al. Genetic predisposition impacts clinical changes in a lifestyle coaching program. Sci. Rep. 9, 6805 (2019).
doi: 10.1038/s41598-019-43058-0
Lundberg, M., Eriksson, A., Tran, B., Assarsson, E. & Fredriksson, S. Homogeneous antibody-based proximity extension assays provide sensitive and specific detection of low-abundant proteins in human blood. Nucleic Acids Res. 39, e102–e102 (2011).
doi: 10.1093/nar/gkr424
Blumenthal, R. D., Leon, E., Hansen, H. J. & Goldenberg, D. M. Expression patterns of CEACAM5 and CEACAM6 in primary and metastatic cancers. BMC Cancer 7, 2 (2007).
doi: 10.1186/1471-2407-7-2
Beauchemin, N. & Arabzadeh, A. Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in cancer progression and metastasis. Cancer Metastasis Rev 32, 643–671 (2013).
doi: 10.1007/s10555-013-9444-6
Sariya, D. et al. Clinicopathologic correlation of cutaneous metastases: experience from a cancer center. Arch. Dermatol 143, 613–620 (2007).
doi: 10.1001/archderm.143.5.613
Cancer Genome Atlas Research Network et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat. Genet.45, 1113–1120 (2013).
Cheung, K., Roman, S. A., Wang, T. S., Walker, H. D. & Sosa, J. A. Calcitonin measurement in the evaluation of thyroid nodules in the United States: a cost-effectiveness and decision analysis. J. Clin. Endocrinol. Metab. 93, 2173–2180 (2008).
doi: 10.1210/jc.2007-2496
Goebell, H. The role of calcium in pancreatic secretion and disease. Acta Hepatogastroenterol (Stuttg) 23, 151–161 (1976).
Fleury, A. et al. Calcitonin-secreting tumors of the pancreas: about six cases. Pancreas 16, 545–550 (1998).
doi: 10.1097/00006676-199805000-00014
Schneider, R. et al. Calcitonin-secreting pancreatic endocrine tumors: systematic analysis of a rare tumor entity. Pancreas 40, 213–221 (2011).
doi: 10.1097/MPA.0b013e3182015f5d
Giannetta, E. et al. Extrathyroidal Calcitonin Secreting Tumors: Pancreatic Neuroendocrine Tumors in Patients With Multinodular Goiter: Two Case Reports. Medicine (Baltimore)95, e2419 (2016).
Delis, S. et al. Asymptomatic calcitonin-secreting tumor of the pancreas: a case report. JOP 7, 70–73 (2006).
pubmed: 16407623
Jensen, C. H. et al. Protein structure of fetal antigen 1 (FA1). A novel circulating human epidermal-growth-factor-like protein expressed in neuroendocrine tumors and its relation to the gene products of dlk and pG2. Eur. J. Biochem.225, 83–92 (1994).
Powell, E. et al. A functional genomic screen in vivo identifies CEACAM5 as a clinically relevant driver of breast cancer metastasis. NPJ Breast Cancer 4, 9 (2018).
doi: 10.1038/s41523-018-0062-x
Fabre-Lafay, S. et al. Nectin-4, a new serological breast cancer marker, is a substrate for tumor necrosis factor-alpha-converting enzyme (TACE)/ADAM-17. J. Biol. Chem. 280, 19543–19550 (2005).
doi: 10.1074/jbc.M410943200
Rodrigues, L. R., Teixeira, J. A., Schmitt, F. L., Paulsson, M. & Lindmark-Mänsson, H. The role of osteopontin in tumor progression and metastasis in breast cancer. Cancer Epidemiol. Biomarkers Prev. 16, 1087–1097 (2007).
doi: 10.1158/1055-9965.EPI-06-1008
Li, B. & Dewey, C. N. RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics 12, 323 (2011).
doi: 10.1186/1471-2105-12-323