Li Hui, Zhou Xiaoping, Zhang Haining, Jiang Jifeng, Fu Hu, Wang Fang
Department of Laboratory Medicine, Chengdu First People's Hospital, Chengdu, Sichuan 610041, China.
Department of Laboratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
J Oncol. 2022 May 20;2022:7271514. doi: 10.1155/2022/7271514. eCollection 2022.
To improve the diagnostic capacity of serum biomarkers for colorectal cancer (CRC), we introduced three novel indicators, namely, the C-X-C motif chemokine ligand 5 (CXCL5), stanniocalcin 2 (STC2), and chitinase 3 like 1 (CHI3L1) and assessed their performances in the detection of CRC.
A total of 887 serum samples (153 health, 342 polyps, and 392 CRCs) were collected. Concentrations of CXCL5, STC2, and CHI3L1 were measured by the ELISA. CEA and CA199 were determined by electrochemiluminescence. Binary logistic regression was used to build the combination model. ROC analysis was used to evaluate the performance of biomarkers alone or in combination.
Model_2 that based on CXCL5, STC2, and CHI3L1 was the best approach in discriminating CRC from non-CRC controls (AUC, 0.943 (0.922-0.960); sensitivity, 0.848; specificity, 0.917; and accuracy, 0.887 in the training cohort and 0.959 (95% CI 0.927-0.980), 0.878, 0.917, and 0.900 in the testing cohort, respectively). In the detection of early CRC, Model_2 revealed AUC, sensitivity, specificity, and accuracy of 0.925 (0.897-0.947), 0.793, 0.917, and 0.886 in the training cohort and those of 0.926 (0.979-0.959), 0.786, 0.931, and 0.898 in the testing cohort. Furthermore, Model_2 exhibited an excellent diagnostic performance in CEA-negative cases (0.938 (0.913-0.957), 0.826, 0.917, and 0.888 in the training cohort and 0.961 (0.925-0.983), 0.887, 0.931, and 0.918 in the testing cohort). As used alone, STC2 achieved the capacities that is second only to that of Model_2 (0.866 (0.837-0.892), 0.859, 0.842, and 0.853 in the training cohort and 0.887 (0.842-0.923), 0.922, 0.799, and 0.853 in the testing cohort). STC2 alone also yielded acceptable results for early CRC detection (0.815 (0.776-0.849), 0.767, 0.849, and 0.829 in the training cohort and 0.870 (0.812-0.914), 0.952, 0.799, and 0.833 in the testing cohort). Moreover, STC2 maintained diagnostic accuracy for CRC patients with negative CEA (0.874 (0.842-0.901), 0.862, 0.849, and 0.853 in the training cohort and 0.898 (0.848-0.936), 0.930, 0.801, and 0.842 in the testing cohort). In comparison, the performances of the CEA and CA199 based Model_1 were far from satisfactory, especially in early cases (0.767 (0.726-0.805), 0.491, 0.863, and 0.771 in the training cohort and 0.817 (0.754-0.870), 0.476, 0.889, and 0.796 in the testing cohort).
STC2 was a promising serum biomarker for CRC diagnosis either used alone or in combination with CXCL5 and CHI3L1.
为提高血清生物标志物对结直肠癌（CRC）的诊断能力，我们引入了三种新指标，即C-X-C基序趋化因子配体5（CXCL5）、骨钙素2（STC2）和几丁质酶3样蛋白1（CHI3L1），并评估了它们在CRC检测中的性能。
共收集了887份血清样本（153份健康样本、342份息肉样本和392份CRC样本）。采用酶联免疫吸附测定法（ELISA）检测CXCL5、STC2和CHI3L1的浓度。采用电化学发光法测定癌胚抗原（CEA）和糖类抗原199（CA199）。使用二元逻辑回归构建组合模型。采用受试者工作特征（ROC）分析评估单个或组合生物标志物的性能。
基于CXCL5、STC2和CHI3L1的模型_2是区分CRC与非CRC对照的最佳方法（在训练队列中，曲线下面积（AUC）为0.943（0.922 - 0.960）；灵敏度为0.848；特异度为0.917；准确度为0.887；在测试队列中分别为0.959（95%置信区间0.927 - 0.980）、0.878、0.917和0.900）。在早期CRC检测中，模型_2在训练队列中的AUC、灵敏度、特异度和准确度分别为0.925（0.897 - 0.947）、0.793、0.917和0.886，在测试队列中分别为0.926（0.979 - 0.959）、0.786、0.931和0.898。此外，模型_2在CEA阴性病例中表现出优异的诊断性能（在训练队列中为0.938（0.913 - 0.957）、0.826、0.917和0.888，在测试队列中为0.961（0.925 - 0.983）、0.887、0.931和0.918）。单独使用时，STC2的性能仅次于模型_2（在训练队列中为0.866（0.837 - 0.892）、0.859、0.842和0.853，在测试队列中为0.887（0.842 - 0.923）、0.922、0.799和0.853）。单独使用STC2在早期CRC检测中也取得了可接受的结果（在训练队列中为0.815（0.776 - 0.849）、0.767、0.849和0.829，在测试队列中为0.870（0.812 - 0.914）、0.952、0.799和0.833）。此外，STC2对CEA阴性的CRC患者保持诊断准确性（在训练队列中为0.874（0.842 - 0.901）、0.862、0.849和0.853，在测试队列中为0.898（0.848 - 0.936）、0.930、0.801和0.842）。相比之下，基于CEA和CA199的模型_1的性能远不能令人满意，尤其是在早期病例中（在训练队列中为0.767（0.726 - 0.805）、0.491、0.863和0.771，在测试队列中为0.817（0.754 - 0.870）、0.476、0.889和0.796）。
STC2无论是单独使用还是与CXCL5和CHI3L1联合使用，都是一种有前景的用于CRC诊断的血清生物标志物。
