Citations 12
A Combined Proteomics and Mendelian Randomization Approach to Investigate the Effects of Aspirin-Targeted Proteins on Colorectal Cancer
Nounu, Aayah , Greenhough, Alexander , Heesom, Kate J. , Richmond, Rebecca C. , Weinstein, Stephanie J. , Baron, John A. , Figueiredo, Jane C. , Lindor, Noralane M. , Casey, Graham , Duijnhoven, Fränzel J.B. van , Gsur, Andrea , Vodička, Pavel , Vodičková, Ludmila, Brenner, Hermann , Chang‐Claude, Jenny , Hoffmeister, Michael , Slattery, Martha L. , Gunter, Marc J. , Kim, Hyeong Rok , Li, Li , Bishop, D. Timothy , Gruber, Stephen B. , Rennert, Gad , Harrison, Tabitha A. , Woods, Michael O. , Schafmayer, Clemens , Guelpen, Bethany Van , Gallinger, Steven , Berndt, Sonja I. , Lindblom, Annika , Wu, Anna H. , White, Emily , Peters, Ulrike , Drew, David A. , Scherer, Dominique , Relton, Caroline L. , Weinstein, Stephanie J , Baron, John A , Platz, Elizabeth A. , van Duijnhoven, Fränzel J B , Gsur, Andrea , Moreno, Victor , Brenner, Hermann , Chang-Claude, Jenny , Hoffmeister, Michael , Sakoda, Lori C , Slattery, Martha L , Schoen, Robert E , Castellví-Bel, Sergi , Kweon, Sun-Seog , Bishop, D Timothy , Buchanan, Daniel D , Giles, Graham G , Gruber, Stephen B , Harrison, Tabitha A , Woods, Michael O , Van Guelpen, Bethany , Hampel, Heather , Pharoah, Paul D P , Wolk, Alicja , Drew, David A , Scherer, Dominique , Rennert, Gad , Gunter, Marc J , Vodicka, Pavel , Lindblom, Annika , Zheng, Jie , Albanes, Demetrius , Hopper, John L. , Newcomb, Polly A. , Marchand, Loı̈c Le , Ulrich, Cornelia M. , Li, Christopher I , Campbell, Peter T. , Moreno, Vı́ctor , Sakoda, Lori C. , Schoen, Robert E. , Castellvı́-Bel, Sergi , Chan, Andrew T. , Zheng, Wei , Buchanan, Daniel D. , Giles, Graham G. , Stadler, Zsofia , Lin, Yi , Keku, Temitope O , Hampel, Heather , Pharoah, Paul D.P. , Wolk, Alicja , Bermejo, Justo Lorenzo , Williams, Ann Caroline
Cancer Epidemiology, Biomarkers & Prevention | January 28, 2021 | Volume: 30 | Issue: 3 | Pages: 564-575
Abstract 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.
Detection and localization of surgically resectable cancers with a multi-analyte blood test
Cohen, Joshua D. , Li, Lu , Wang, Yuxuan , Thoburn, Christopher J. , Danilova, Ludmila , Douville, Christopher , Javed, Ammar A. , Wong, Fay , Mattox, Austin K. , Hruban, Ralph H. , Wolfgang, Christopher L. , Molin, Marco Dal , Ptak, Janine , Dobbyn, Lisa , Silliman, Natalie , Browne, J. Dale, Tie, Jeanne , Wong, Hui‐Li , Mansfield, Aaron S. , Jen, Jin , Falconi, Massimo , Allen, Peter J. , Zhou, Shibin , Díaz, Luis A. , Kinzler, Kenneth W. , Vogelstein, Bert , Lennon, Anne Marie , Papadopoulos, Nickolas , Thoburn, Christopher , Danilova, Ludmila , Douville, Christopher , Javed, Ammar A , Wong, Fay , Mattox, Austin , Wolfgang, Christopher L , Roden, Richard , Klein, Alison P , Ptak, Janine , Dobbyn, Lisa , Schaefer, Joy , Silliman, Natalie , Schoen, Robert E , Brand, Randall E , Tie, Jeanne , Wong, Hui-Li , Mansfield, Aaron S , Jen, Jin , Zhou, Shibin , Diaz, Luis A , Tomasetti, Cristian , Kinzler, Kenneth W , Vogelstein, Bert , Lennon, Anne Marie , Papadopoulos, Nickolas , Wang, Yuxuan , Afsari, Bahman , Goggins, Michael , Wang, Tian‐Li , Klein, Alison P. , Popoli, Maria , Vogelstein, Joshua T , Schoen, Robert E. , Brand, Randall E. , Gibbs, Peter , Hanash, Samir , Bettegowda, Chetan , Massimo, Falconi
Science | January 18, 2018 | Volume: 359 | Issue: 6378 | Pages: 926-930
SEEK and you may find cancer earlier Many cancers can be cured by surgery and/or systemic therapies when detected before they have metastasized. This clinical reality, coupled with the growing appreciation that cancer's rapid genetic evolution limits its response to drugs, have fueled interest in methodologies for earlier detection of the disease. Cohen et al. developed a noninvasive blood test, called CancerSEEK that can detect eight common human cancer types (see the Perspective by Kalinich and Haber). The test assesses eight circulating protein biomarkers and tumor-specific mutations in circulating DNA. In a study of 1000 patients previously diagnosed with cancer and 850 healthy control individuals, CancerSEEK detected cancer with a sensitivity of 69 to 98% (depending on cancer type) and 99% specificity. Science , this issue p. 926 ; see also p. 866