Associations of Biomarkers of Systemic Inflammation, Angiogenesis, and Cell-to-Cell Adhesion With Tumor Budding Among Early-Onset and Later-Onset Colorectal Cancer Patients

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2025-09-23 DOI:10.1002/cam4.71267

Oda Hausmann, Pauline P. Schobert, Jennifer Ose, Caroline Himbert, Maria Pletneva, Jolanta Jedrzkiewicz, Anne Nguyen, Tengda Lin, Christy A. Warby, Sheetal Hardikar, Anita R. Peoples, Ildiko Strehli, Lyen C. Huang, Jessica N. Cohan, Bartley Pickron, Courtney Scaife, Christopher I. Li, William M. Grady, David Shibata, Adetunji T. Toriola, Martin Schneider, Jane C. Figueiredo, Erin M. Siegel, Biljana Gigic, Stephan Herzig, Mmadili N. Ilozumba, Cornelia M. Ulrich

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Abstract

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.

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早发性和晚发性结直肠癌患者全身炎症、血管生成和细胞间粘附生物标志物与肿瘤萌芽的关系

背景：肿瘤高出芽和全身炎症升高是结直肠癌的不良预后指标。其潜在机制仍然知之甚少。目前尚不清楚全身性炎症、血管生成和细胞间粘附是否影响肿瘤出芽。方法：我们调查了亨茨曼癌症研究所招募的n = 132名参加ColoCare研究的I-III期结直肠癌患者。使用循证评分系统评估肿瘤出芽，使用Meso Scale Discovery平台分析患者血清中的9种循环生物标志物。我们通过调整年龄、性别、新辅助治疗、分期和非甾体抗炎药使用的多变量线性回归模型检验了生物标志物与肿瘤出芽之间的关系。结果：研究人群主要是非西班牙裔白人（95%），平均年龄61岁；56%是男性。大多数肿瘤为III期（47%），位于结肠（64%），表现为低级别肿瘤出芽（58%）。可溶性细胞间粘附分子1与肿瘤出芽总体呈负相关（M1: β = -0.57, p = 0.03），在女性（M1: β = -0.81， p值= 0.03）和晚发（≥50岁）结直肠癌（M1: β = -0.71， p值= 0.008）中呈负相关。男性患者c反应蛋白与肿瘤出芽呈正相关（M1: β = 0.23, p = 0.001），白介素-8 （M1: β = 0.96， p值= 0.01）和可溶性血管粘附分子1 （M2: β = 1.48， p值= 0.04）与肿瘤出芽呈正相关。然而，在多重检验校正后，这些关联并没有保持统计学显著性。结论：总的来说，我们的研究结果并没有提供系统性炎症、血管生成和细胞间粘附的生物标志物与肿瘤出芽计数之间的显著关联的证据。我们观察到一些生物标志物的模式，但经过多次测试校正后，没有一个仍然具有统计学意义。这些发现为未来的研究提供了初步的见解。试验注册：ClinicalTrials.gov: NCT02328677。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.