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| 血清CBLL1 ADAMTS13 CHI3L1水平与结直肠癌患者与化疗心脏毒性的关系及预后评估价值 |
| Relationship between serum CBLL1, ADAMTS13, CHI3L1 levels with chemotherapy-induced cardiac toxicity in colorectal cancer patients and their prognostic evaluation value |
| 投稿时间：2025-10-15 |
| DOI：10.3969/j.issn.1000-0399.2026.06.003 |
| 中文关键词: 结直肠癌 E3泛素连接酶 血管性血友病因子裂解蛋白酶13 几丁质酶-3样蛋白1 心脏毒性 |
| 英文关键词: Colorectal cancer Casitas B lineage lymphoma A disintegrin like and metalloproteinase with thrombospondin type Ⅰ motif 13 Chitinase-3-like protein 1 Cardiac toxicity |
| 基金项目:河北省健康委员会资助项目(编号:20261382) |
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| 中文摘要: |
| 目的 探讨血清E3泛素连接酶（CBLL1）、血管性血友病因子裂解蛋白酶13(ADAMTS13)、几丁质酶-3样蛋白1(CHI3L1)水平与结直肠癌患者与化疗心脏毒性的关系及预后评估价值。方法 本研究属于前瞻性研究。选取石家庄市第二医院普外科于2020年2月至2022年4月收治的结直肠癌患者153例（病例组），根据患者是否发生化疗相关心脏毒性事件分为心脏毒性组（35例）与无心脏毒性组（118例）；根据患者的预后情况分为预后良好组（109例）、预后不良组（44例）。另选取同期80例结直肠良性病变患者作为对照组。酶联免疫吸附测定（ELISA）法检测血清CBLL1、ADAMTS13、CHI3L1水平；相对危险度分析对结直肠癌患者预后的影响；受试者工作特征（ROC）曲线评估血清CBLL1、ADAMTS13、CHI3L1对结直肠癌患者预后不良的预测价值；决策曲线评估血清CBLL1、ADAMTS13、CHI3L1预测模型的临床净效益率。结果 与对照组相比，病例组血清CBLL1、CHI3L1水平升高，ADAMTS13水平降低，差异有统计学意义（P<0.001）；与无心脏毒性组相比，心脏毒性组血清CBLL1、CHI3L1水平升高，ADAMTS13水平降低，差异有统计学意义（P<0.001）；与预后良好组相比，预后不良组血清CBLL1、CHI3L1、CEA、CA199水平及淋巴结转移、低分化患者占比升高，ADAMTS13水平降低，差异有统计学意义（P<0.05）；血清CBLL1、CHI3L1高水平患者发生预后不良风险是低水平患者的2.176倍、2.007倍（P=0.004、0.009），血清ADAMTS13低水平患者发生预后不良风险是高水平患者的2.060倍（P=0.007）；血清CBLL1、ADAMTS13、CHI3L1联合预测结直肠癌患者预后不良的曲线下面积（AUC）均高于CBLL1(Z=3.818,P<0.001)、ADAMTS13(Z=3.967,P<0.001)、CHI3L1(Z=3.949,P<0.001)单独检测，联合预测的灵敏度、特异度分别为95.45%、76.15%；高风险阈值在0.06～0.92时，血清CBLL1、ADAMTS13、CHI3L1联合预测模型的净效益率高于单一指标。结论 结直肠癌患者血清CBLL1、CHI3L1水平升高，ADAMTS13水平降低，与发生化疗心脏毒性相关，3者联合对结直肠癌患者预后不良具有较高的预测价值。 |
| 英文摘要: |
| Objective To investigate the relationship between serum levels of casitas B lineage lymphoma(CBLL1), a disintegrin like and metalloproteinase with thrombospondin type Ⅰ motif 13(ADAMTS13) and chitinase-3-like protein 1(CHI3L1) and chemotherapy-induced cardiotoxicity in patients with colorectal cancer, as well as their prognostic value. Methods This prospective study recruited a total of 153 patients(case group) with colorectal cancer admitted to the Department of General Surgery at Shijiazhuang Second Hospital between February 2020 and April 2022. Patients were divided into a cardiotoxic group(35 cases) and a non-cardiotoxic group(118 cases) based on whether they experienced chemotherapy-related cardiotoxicity events. Patients were divided into a group with a favourable prognosis(109 cases) and a group with an unfavourable prognosis(44 cases) based on their prognosis. Another 80 patients with benign colorectal lesions were served as the control group. ELISA method was used to detect levels of serum CBLL1, ADAMTS13, and CHI3L1. Relative risk was used to discuss the impact on the prognosis of colorectal cancer patients. Receiver operating characteristic(ROC) curve was used to evaluate the predictive value of serum CBLL1, ADAMTS13, and CHI3L1 for adverse prognosis in colorectal cancer patients. In addition, the decision curve was used to evaluate the clinical net benefit of the serum CBLL1, ADAMTS13, and CHI3L1 prediction models. Results Compared with the control group, the case group exhibited elevated serum levels of CBLL1 and CHI3L1 and reduced levels of ADAMTS13, with these differences being statistically significant(P<0.001). Compared with the non-cardiotoxic group, the cardiotoxic group exhibited significantly higher serum levels of CBLL1 and CHI3L1 and significantly lower levels of ADAMTS13(P<0.001). Compared with the favourable prognosis group, the unfavourable prognosis group exhibited higher serum levels of CBLL1, CHI3L1, CEA and CA199, as well as a higher proportion of patients with lymph node metastasis and poorly differentiated tumours; conversely, ADAMTS13 levels were lower, with these differences being statistically significant(P<0.05). Patients with elevated serum CBLL1 and CHI3L1 levels exhibited a 2.176-fold and 2.007-fold increased risk of poor prognosis, respectively, compared to those with low levels(P=0.004, P=0.009). Patients with low serum ADAMTS13 levels demonstrated a 2.060-fold increased risk of poor prognosis relative to those with high levels(P=0.007). The area under the curve(AUC) for the combined prediction of poor prognosis in colorectal cancer patients using serum CBLL1, ADAMTS13 and CHI3L1 was higher than that for CBLL1(Z=3.818, P<0.001), ADAMTS13(Z=3.967, P<0.001) and CHI3L1(Z=3.949, P<0.001) when assessed individually; the sensitivity and specificity of the combined prediction was 95.45% and 76.15%, respectively. The combined prediction demonstrated a sensitivity of 95.45% and specificity of 76.15%. When the high-risk threshold was between 0.06 and 0.92, the net benefit rate of the combined prediction model of serum CBLL1, ADAMTS13, and CHI3L1 was higher than that of a single indicator. Conclusion Elevated serum levels of CBLL1 and CHI3L1, and reduced levels of ADAMTS13, are associated with the development of chemotherapy-induced cardiotoxicity in patients with colorectal cancer; the combination of these three markers has high predictive value for poor prognosis in such patients. |
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