Počet záznamů: 1
A Combined Proteomics and Mendelian Randomization Approach to Investigate the Effects of Aspirin-Targeted Proteins on Colorectal Cancer
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SYSNO ASEP 0552718 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název A Combined Proteomics and Mendelian Randomization Approach to Investigate the Effects of Aspirin-Targeted Proteins on Colorectal Cancer Tvůrce(i) Nounu, A. (GB)
Greenhough, A. (GB)
Heesom, K.J. (GB)
Richmond, R.C. (GB)
Zheng, J. (GB)
Weinstein, S.J. (US)
Albanes, D. (US)
Baron, J.A. (US)
Hopper, J.L. (AU)
Figueiredo, J.C. (US)
Newcomb, P.A. (US)
Lindor, N.M. (US)
Casey, G. (US)
Platz, E.A. (US)
Le Marchand, L. (US)
Ulrich, C.M. (US)
Li, Ch.I. (US)
van Duijnhoven, F.J.B. (NL)
Gsur, A. (AT)
Campbell, C. T. (US)
Moreno, V. (ES)
Vodička, Pavel (UEM-P) RID
Vodičková, Ludmila (UEM-P) RID
Brenner, H. (DE)
Chang-Claude, J. (DE)
Hoffmeister, M. (DE)
Sakoda, L.C. (US)
Slattery, J.M. (US)
Schoen, R.E. (US)
Gunter, M.J. (FR)
Castellví-Bel, S. (ES)
Kim, H.R. (KR)
Kweon, S.S. (KR)
Chan, A.T. (US)
Li, L. (US)
Zheng, W. (US)
Bishop, D.T. (US)
Buchanan, D.D. (AT)
Giles, G.G. (AU)
Gruber, S.B. (US)
Rennert, G. (IL)
Stadler, Z.K. (US)
Harrison, T.A. (US)
Lin, Y. (US)
Keku, T.O. (US)
Woods, M.O. (CA)
Schafmayer, C. (DE)
Van Guelpen, B. (SE)
Gallinger, S. (CA)
Hampel, H. (US)
Berndt, S.I. (US)
Pharoah, P.D.P. (GB)
Lindblom, A. (SE)
Wolk, A. (US)
Wu, A.H. (US)
White, E. (US)
Peters, U. (US)
Drew, D.A. (US)
Scherer, D. (DE)
Bermejo, J. L. (DE)
Williams, A.C. (GB)
Relton, C.L. (GB)Zdroj.dok. Cancer Epidemiology Biomarkers & Prevention. - : American Association for Cancer Research - ISSN 1055-9965
Roč. 30, č. 3 (2021), s. 564-575Poč.str. 12 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova regulatory variation ; follow-up ; instruments ; risk ; association ; expression ; mutations Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Genetics and heredity (medical genetics to be 3) CEP GAP304/10/1286 GA ČR - Grantová agentura ČR NV15-27580A GA MZd - Ministerstvo zdravotnictví NV17-30920A GA MZd - Ministerstvo zdravotnictví Způsob publikování Open access Institucionální podpora UEM-P - RVO:68378041 UT WOS 000627591100020 EID SCOPUS 85099407187 DOI 10.1158/1055-9965.EPI-20-1176 Anotace Background: Evidence for aspirin's chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk.
Methods: Human colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labeling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL (N = 3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium (N = 31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was performed using eQTL/pQTL data combined with CRC genetic summary data from the Colon Cancer Family Registry (CCFR), Colorectal Transdisciplinary (CORECT), Genetics and Epidemiology of Colorectal Cancer (GECCO) consortia and UK Biobank (55,168 cases and 65,160 controls).
Results: Altered expression was detected for 125/5886 proteins. Of these, aspirin decreased MCM6, RRM2, and ARFIP2 expression, and MR analysis showed that a standard deviation increase in mRNA/protein expression was associated with increased CRC risk (OR: 1.08, 95% CI, 1.03-1.13, OR: 3.33, 95% CI, 2.46-4.50, and OR: 1.15, 95% CI, 1.02-1.29, respectively).
Conclusions: MCM6 and RRM2 are involved in DNA repair whereby reduced expression may lead to increased DNA aberrations and ultimately cancer cell death, whereas ARFIP2 is involved in actin cytoskeletal regulation, indicating a possible role in aspirin's reduction of metastasis.
Impact: Our approach has shown how laboratory experiments and population-based approaches can combine to identify aspirin-targeted proteins possibly affecting CRC risk.Pracoviště Ústav experimentální medicíny Kontakt Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Rok sběru 2022 Elektronická adresa https://cebp.aacrjournals.org/content/30/3/564
Počet záznamů: 1