TY - JOUR
T1 - Associations of Biomarkers of Systemic Inflammation, Angiogenesis, and Cell-to-Cell Adhesion With Tumor Budding Among Early-Onset and Later-Onset Colorectal Cancer Patients
AU - Hausmann, Oda
AU - Schobert, Pauline P.
AU - Ose, Jennifer
AU - Himbert, Caroline
AU - Pletneva, Maria
AU - Jedrzkiewicz, Jolanta
AU - Nguyen, Anne
AU - Lin, Tengda
AU - Warby, Christy A.
AU - Hardikar, Sheetal
AU - Peoples, Anita R.
AU - Strehli, Ildiko
AU - Huang, Lyen C.
AU - Cohan, Jessica N.
AU - Pickron, Bartley
AU - Scaife, Courtney
AU - Li, Christopher I.
AU - Grady, William M.
AU - Shibata, David
AU - Toriola, Adetunji T.
AU - Schneider, Martin
AU - Figueiredo, Jane C.
AU - Siegel, Erin M.
AU - Gigic, Biljana
AU - Herzig, Stephan
AU - Ilozumba, Mmadili N.
AU - Ulrich, Cornelia M.
N1 - Publisher Copyright:
© 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.
PY - 2025/9
Y1 - 2025/9
N2 - Background: High tumor budding and elevated systemic inflammation are adverse prognostic indicators in colorectal cancer. Its underlying mechanisms remain poorly understood. It is unclear whether systemic inflammation, angiogenesis, and cell-to-cell adhesion influence tumor budding. Methods: We investigated n = 132 stage I–III colorectal cancer patients recruited at Huntsman Cancer Institute enrolled in the ColoCare Study. Tumor budding was evaluated using an evidence-based scoring system, and patient sera were analyzed for nine circulating biomarkers using the Meso Scale Discovery platform. We examined associations between biomarkers and tumor budding using multivariable linear regression models adjusted for age, sex, neoadjuvant treatment, stage, and non-steroidal anti-inflammatory drug use. Results: The study population was predominantly non-Hispanic White (95%), with a mean age of 61 years; 56% were male. Most tumors were stage III (47%), located in the colon (64%), and exhibited low-grade tumor budding (58%). Soluble intercellular adhesion molecule 1 was inversely associated with tumor budding overall (M1: β = −0.57, p = 0.03), among females (M1: β = −0.81, p-value = 0.03) and later-onset (≥ 50 years) colorectal cancer (M1: β = −0.71, p-value = 0.008). C-reactive protein was positively associated with tumor budding in males (M1: β = 0.23, p = 0.001), while interleukin-8 (M1: β = 0.96, p-value = 0.01) and soluble vascular adhesion molecule 1 (M2: β = 1.48, p-value = 0.04) were positively associated with tumor budding in early-onset patients. However, these associations did not remain statistically significant after correction for multiple testing. Conclusion: Overall, our findings do not provide evidence of a significant association between biomarkers of systemic inflammation, angiogenesis, and cell-to-cell adhesion with tumor budding count. We observed patterns for some biomarkers, yet none remained statistically significant after correction for multiple testing. These findings provide preliminary insights for future studies. Trial Registration: ClinicalTrials.gov: NCT02328677.
AB - Background: High tumor budding and elevated systemic inflammation are adverse prognostic indicators in colorectal cancer. Its underlying mechanisms remain poorly understood. It is unclear whether systemic inflammation, angiogenesis, and cell-to-cell adhesion influence tumor budding. Methods: We investigated n = 132 stage I–III colorectal cancer patients recruited at Huntsman Cancer Institute enrolled in the ColoCare Study. Tumor budding was evaluated using an evidence-based scoring system, and patient sera were analyzed for nine circulating biomarkers using the Meso Scale Discovery platform. We examined associations between biomarkers and tumor budding using multivariable linear regression models adjusted for age, sex, neoadjuvant treatment, stage, and non-steroidal anti-inflammatory drug use. Results: The study population was predominantly non-Hispanic White (95%), with a mean age of 61 years; 56% were male. Most tumors were stage III (47%), located in the colon (64%), and exhibited low-grade tumor budding (58%). Soluble intercellular adhesion molecule 1 was inversely associated with tumor budding overall (M1: β = −0.57, p = 0.03), among females (M1: β = −0.81, p-value = 0.03) and later-onset (≥ 50 years) colorectal cancer (M1: β = −0.71, p-value = 0.008). C-reactive protein was positively associated with tumor budding in males (M1: β = 0.23, p = 0.001), while interleukin-8 (M1: β = 0.96, p-value = 0.01) and soluble vascular adhesion molecule 1 (M2: β = 1.48, p-value = 0.04) were positively associated with tumor budding in early-onset patients. However, these associations did not remain statistically significant after correction for multiple testing. Conclusion: Overall, our findings do not provide evidence of a significant association between biomarkers of systemic inflammation, angiogenesis, and cell-to-cell adhesion with tumor budding count. We observed patterns for some biomarkers, yet none remained statistically significant after correction for multiple testing. These findings provide preliminary insights for future studies. Trial Registration: ClinicalTrials.gov: NCT02328677.
KW - colorectal cancer
KW - CRP
KW - early-onset colorectal cancer
KW - IL-8
KW - sICAM-1
KW - systemic inflammation
KW - tumor budding
UR - https://www.scopus.com/pages/publications/105016772214
U2 - 10.1002/cam4.71267
DO - 10.1002/cam4.71267
M3 - Article
C2 - 40985344
AN - SCOPUS:105016772214
SN - 2045-7634
VL - 14
JO - Cancer medicine
JF - Cancer medicine
IS - 18
M1 - e71267
ER -