TY - JOUR
T1 - Presurgery Adhesion Molecules and Angiogenesis Biomarkers Are Differently Associated with Outcomes in Colon and Rectal Cancer
T2 - Results from the ColoCare Study
AU - Ose, Jennifer
AU - Gigic, Biljana
AU - Hardikar, Sheetal
AU - Lin, Tengda
AU - Himbert, Caroline
AU - Warby, Christy A.
AU - Peoples, Anita R.
AU - Lindley, Clara L.
AU - Boehm, Juergen
AU - Schrotz-King, Petra
AU - Figueiredo, Jane C.
AU - Toriola, Adetunji T.
AU - Siegel, Erin M.
AU - Li, Christopher I.
AU - Ulrich, Alexis
AU - Schneider, Martin
AU - Shibata, David
AU - Ulrich, Cornelia M.
N1 - Funding Information:
J. Ose, B. Gigic, C.I. Li, D. Shibata, and C.M. Ulrich received funding by the NIH R01189184. B. Gigic and C.M. Ulrich received funding by the German Consortium of Translational Cancer Research (DKTK) and the German Cancer Research Center (Division of Preventive Oncology). C. Himbert and C.M. Ulrich are supported by NIH R01 CA211705. C. Himbert was supported by the Stiftung LebensBlicke and Claussen-Simon Stiftung, Germany. C. Himbert, Lin T, Warby C.A., J. Ose, and C.M. Ulrich received funding by the Huntsman Cancer Foundation. C.M. Ulrich received funding for the Heidelberg ColoCare Study by the Matthias Lackas Foundation. B. Gigic, J. Boehm, and C.M. Ulrich received funding from the Transcan-ERANET grant 01KT1503 (FOCUS consortium) and institutional funding.
Funding Information:
We thank our collaborators on the ColoCare recruitment, particularly Hermann Brenner, Jenny Chang-Claude, and Michael Hoffmeister. We are grateful to all the study staff who have made this study possible: (1) from Heidelberg: Torsten K€olsch, Susanne Jakob, Clare Abbenhardt, Werner Diehl, Rifraz Farook, Lin Zielske, Anett Brendel, Marita Wenzel, Renate Skatula, and (2) from Salt Lake City: Karen Salas, Sarah Fischbuch, and Tyler Farr. J. Ose, B. Gigic, S. Hardikar, T. Lin, C. Himbert, C.A. Warby, J. Boehm, J.C. Figueiredo, A.T. Toriola, E.M. Siegel, C.I. Li, A. Ulrich, M. Schneider, D. Shibata, and C.M. Ulrich received funding by the NIH U01CA206110. J. Ose, B. Gigic, C.A. Warby, J. Boehm, J.C. Figueiredo, A.T. Toriola, E.M. Siegel, C.I. Li, and C.M. Ulrich received funding by NIH R01CA207371. J. Ose, B. Gigic, C.I. Li, D. Shibata, and C.M. Ulrich received funding by the NIH R01189184. B. Gigic and C.M. Ulrich received funding by the German Consortium of Translational Cancer Research (DKTK) and the German Cancer Research Center (Division of Preventive Oncology). C. Himbert and C.M. Ulrich are supported by NIH R01 CA211705. C. Himbert was supported by the Stiftung LebensBlicke and Claussen-Simon Stiftung, Germany. C. Himbert, Lin T, Warby C.A., J. Ose, and C.M. Ulrich received funding by the Huntsman Cancer Foundation. C.M. Ulrich received funding for the Heidelberg ColoCare Study by the Matthias Lackas Foundation. B. Gigic, J. Boehm, and C.M. Ulrich received funding from the Transcan-ERANET grant 01KT1503 (FOCUS consortium) and institutional funding.
Funding Information:
B. Gigic reports grants from NIH and BMBF during the conduct of the study. C.A. Warby reports other support from Huntsman Cancer Foundation, grants from Huntsman Cancer Institute, University of Utah, and NIH during the conduct of the study. E.M. Siegel reports grants from NIH NCI during the conduct of the study. C.M. Ulrich reports grants from NIH during the conduct of the study. No disclosures were reported by the other authors.
Publisher Copyright:
©2022 American Association for Cancer Research.
PY - 2022/8
Y1 - 2022/8
N2 - Background: Cell-to-cell adhesion and angiogenesis are hallmarks of cancer. No studies have examined associations of adhesion molecules and angiogenesis biomarkers with clinical outcomes in colorectal cancer. Methods: In presurgery serum from n ¼ 426 patients with colorectal cancer (stage I–III), we investigated associations of CRP, SAA, adhesion molecules (sICAM-1, sVCAM-1), and angiogenesis markers (VEGF-A and VEGF-D) with overall survival (OS), disease-free survival (DFS), and risk of recurrence. We computed HRs and 95% confidence intervals; adjusted for age, sex, BMI, stage, site, and study site, stratified by tumor site in exploratory analyses. Results: N ¼ 65 (15%) were deceased, and 39 patients (14%) had a recurrence after a median follow-up of 31 months. We observed significant associations of biomarkers with OS, DFS, and risk of recurrence on a continuous scale and comparing top to bottom tertile, with HRs ranging between 1.19 and 13.92. CRP was associated with risk of death and recurrence in patients in the top tertile compared with patients in the bottom tertile, for example, risk of recurrence HRQ3-Q1: 13.92 (1.72–112.56). Significant heterogeneity between biomarkers and clinical outcomes was observed in stratified analysis by tumor site for CRP, SAA, sICAM-1, sVCAM-1, and VEGF-D. VEGF-D was associated with a 3-fold increase in risk of death for rectal cancer (HRlog2: 3.26; 95% CI, 1.58–6.70) compared with no association for colon cancer (HRlog2: 0.78; 95% CI, 0.35–1.73; Pheterogenity ¼ 0.01). Conclusions: Adhesion molecules and angiogenesis biomarkers are independent prognostic markers for colorectal cancer, with differences by tumor site. Impact: There is need for tailored treatment for colon and rectal cancer.
AB - Background: Cell-to-cell adhesion and angiogenesis are hallmarks of cancer. No studies have examined associations of adhesion molecules and angiogenesis biomarkers with clinical outcomes in colorectal cancer. Methods: In presurgery serum from n ¼ 426 patients with colorectal cancer (stage I–III), we investigated associations of CRP, SAA, adhesion molecules (sICAM-1, sVCAM-1), and angiogenesis markers (VEGF-A and VEGF-D) with overall survival (OS), disease-free survival (DFS), and risk of recurrence. We computed HRs and 95% confidence intervals; adjusted for age, sex, BMI, stage, site, and study site, stratified by tumor site in exploratory analyses. Results: N ¼ 65 (15%) were deceased, and 39 patients (14%) had a recurrence after a median follow-up of 31 months. We observed significant associations of biomarkers with OS, DFS, and risk of recurrence on a continuous scale and comparing top to bottom tertile, with HRs ranging between 1.19 and 13.92. CRP was associated with risk of death and recurrence in patients in the top tertile compared with patients in the bottom tertile, for example, risk of recurrence HRQ3-Q1: 13.92 (1.72–112.56). Significant heterogeneity between biomarkers and clinical outcomes was observed in stratified analysis by tumor site for CRP, SAA, sICAM-1, sVCAM-1, and VEGF-D. VEGF-D was associated with a 3-fold increase in risk of death for rectal cancer (HRlog2: 3.26; 95% CI, 1.58–6.70) compared with no association for colon cancer (HRlog2: 0.78; 95% CI, 0.35–1.73; Pheterogenity ¼ 0.01). Conclusions: Adhesion molecules and angiogenesis biomarkers are independent prognostic markers for colorectal cancer, with differences by tumor site. Impact: There is need for tailored treatment for colon and rectal cancer.
UR - http://www.scopus.com/inward/record.url?scp=85135597671&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-22-0092
DO - 10.1158/1055-9965.EPI-22-0092
M3 - Article
C2 - 35667092
AN - SCOPUS:85135597671
SN - 1055-9965
VL - 31
SP - 1650
EP - 1660
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 8
ER -