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术前黏附分子和血管生成生物标志物与结直肠癌的结局具有不同相关性:ColoCare 研究的结果。

Presurgery Adhesion Molecules and Angiogenesis Biomarkers Are Differently Associated with Outcomes in Colon and Rectal Cancer: Results from the ColoCare Study.

机构信息

University of Utah, Salt Lake City, Utah.

Huntsman Cancer Institute, Salt Lake City, Utah.

出版信息

Cancer Epidemiol Biomarkers Prev. 2022 Aug 2;31(8):1650-1660. doi: 10.1158/1055-9965.EPI-22-0092.

Abstract

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 = 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 = 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 = 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.

摘要

背景

细胞间黏附与血管生成是癌症的特征。目前尚无研究探讨黏附分子和血管生成生物标志物与结直肠癌患者临床结局的相关性。

方法

在 n = 426 例结直肠癌(Ⅰ-Ⅲ 期)患者术前血清中,我们研究了 C 反应蛋白(CRP)、血清淀粉样蛋白 A(SAA)、黏附分子(可溶性细胞间黏附分子-1 [sICAM-1]、可溶性血管细胞黏附分子-1 [sVCAM-1])和血管生成标志物(血管内皮生长因子 A [VEGF-A]和 VEGF-D)与总生存期(OS)、无病生存期(DFS)和复发风险的相关性。我们计算了 HRs 和 95%置信区间;并根据年龄、性别、BMI、分期、部位和研究地点进行了调整,在探索性分析中按肿瘤部位进行了分层。

结果

n = 65(15%)患者死亡,39 例(14%)患者在中位随访 31 个月后复发。我们发现,生物标志物与 OS、DFS 和连续尺度及按三分位数比较的复发风险均存在显著相关性,HR 范围为 1.19-13.92。与下三分位相比,CRP 在上三分位的患者死亡和复发风险更高,例如,复发风险 HRQ3-Q1:13.92(1.72-112.56)。CRP、SAA、sICAM-1、sVCAM-1 和 VEGF-D 的肿瘤部位分层分析显示,生物标志物与临床结局之间存在显著异质性。与结肠癌相比,VEGF-D 与直肠癌死亡风险增加 3 倍相关(HRlog2:3.26;95%CI,1.58-6.70)(Pheterogenity = 0.01)。

结论

黏附分子和血管生成生物标志物是结直肠癌的独立预后标志物,且与肿瘤部位有关。

影响

需要针对结肠癌和直肠癌进行个体化治疗。

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