Research Programs Unit, Translational Cancer Medicine, University of Helsinki, Helsinki, Finland.
Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland.
Oncology. 2022;100(1):22-30. doi: 10.1159/000518956. Epub 2021 Nov 18.
Colorectal cancer is the third most common cancer worldwide, with an obvious need for more accurate prognostics. Previous studies identified C-reactive protein (CRP) as a prognostic serum biomarker for colorectal cancer, whereas the biomarkers tumor-associated trypsin inhibitor (TATI) and tumor-associated trypsin-2 (TAT-2) are less well-known prognostic factors. Therefore, in this study, we aimed to compare the prognostic role of these biomarkers.
Our cohort consisted of 219 women and 274 men who underwent colorectal cancer surgery at Helsinki University Central Hospital from 1998 through 2005. Serum and plasma samples were collected before surgery, aliquoted, stored at -80°C, and then analyzed using high-sensitivity methods with commercially available time-resolved immunofluorometric assay kits.
In univariate analysis, CRP (HR 1.67; 95% confidence interval [CI]: 1.25-2.23; p = 0.001), TATI (HR 1.87; 95% CI: 1.13-3.08; p = 0.014), and TAT-2 (HR 1.52; 95% CI: 1.13-2.06; p = 0.006) were significant prognostic biomarkers across the entire cohort. In subgroup analyses, TATI and TAT-2 represented significant negative prognostic factors among patients older than 66, while patients with left-sided disease, a high serum TAT-2, or a high plasma CRP experienced worse prognosis. None of the biomarkers emerged as important in the disease stage subgroup analysis nor did they serve as independent factors in the multivariate analysis.
TATI and TAT-2 as well as CRP significantly, but not independently, served as prognostic factors in our cohort of colorectal cancer patients. Further research is needed to fully understand their clinical role in colorectal cancer.
结直肠癌是全球第三大常见癌症,显然需要更准确的预后判断。先前的研究已确定 C 反应蛋白(CRP)为结直肠癌的一种预后血清生物标志物,而肿瘤相关胰蛋白酶抑制剂(TATI)和肿瘤相关胰蛋白酶-2(TAT-2)则是不太知名的预后因素。因此,本研究旨在比较这些生物标志物的预后作用。
我们的队列包括 219 名女性和 274 名男性,他们于 1998 年至 2005 年在赫尔辛基大学中心医院接受了结直肠癌手术。在手术前采集血清和血浆样本,等分,储存在-80°C 下,然后使用商业上可用的高灵敏度时间分辨免疫荧光分析试剂盒进行分析。
在单因素分析中,CRP(HR 1.67;95%置信区间[CI]:1.25-2.23;p = 0.001)、TATI(HR 1.87;95% CI:1.13-3.08;p = 0.014)和 TAT-2(HR 1.52;95% CI:1.13-2.06;p = 0.006)在整个队列中是显著的预后生物标志物。在亚组分析中,TATI 和 TAT-2 在年龄大于 66 岁的患者中是显著的负预后因素,而左半结肠癌、高血清 TAT-2 或高血浆 CRP 的患者预后较差。在疾病分期亚组分析中,没有一个生物标志物是重要的,在多因素分析中也不是独立的因素。
TATI、TAT-2 和 CRP 在我们的结直肠癌患者队列中显著但非独立地作为预后因素。需要进一步的研究来充分了解它们在结直肠癌中的临床作用。