早发型和晚发型结直肠癌患者中全身炎症、血管生成及细胞间黏附生物标志物与肿瘤芽生的相关性

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

作者信息

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

机构信息

Huntsman Cancer Institute, Salt Lake City, Utah, USA.

Department of Population Health Sciences, University of Utah, Salt Lake City, Utah, USA.

出版信息

Cancer Med. 2025 Sep;14(18):e71267. doi: 10.1002/cam4.71267.

DOI:10.1002/cam4.71267

PMID:40985344

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12455364/

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.

摘要

背景

高肿瘤芽生与全身炎症反应增强是结直肠癌不良预后的指标。其潜在机制仍知之甚少。全身炎症、血管生成和细胞间黏附是否影响肿瘤芽生尚不清楚。

方法

我们调查了亨茨曼癌症研究所招募的132例I-III期结直肠癌患者，这些患者均参与了ColoCare研究。使用基于证据的评分系统评估肿瘤芽生情况，并使用Meso Scale Discovery平台分析患者血清中的9种循环生物标志物。我们使用经年龄、性别、新辅助治疗、分期和非甾体抗炎药使用情况校正的多变量线性回归模型，研究生物标志物与肿瘤芽生之间的关联。

结果

研究人群主要为非西班牙裔白人（95%），平均年龄61岁；56%为男性。大多数肿瘤为III期（47%），位于结肠（64%），且肿瘤芽生程度低（58%）。可溶性细胞间黏附分子1与总体肿瘤芽生呈负相关（模型1：β=-0.57，p=0.03），在女性中（模型1：β=-0.81，p值=0.03）以及在发病较晚（≥50岁）的结直肠癌患者中（模型1：β=-0.71，p值=0.008）也是如此。C反应蛋白在男性中与肿瘤芽生呈正相关（模型1：β=0.23，p=0.001），而白细胞介素-8（模型1：β=0.96，p值=0.01）和可溶性血管黏附分子1（模型2：β=1.48，p值=0.04）在发病较早的患者中与肿瘤芽生呈正相关。然而，在进行多重检验校正后，这些关联不再具有统计学意义。