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基于剂量反应模型分析血清CXCL9、FABP5 水平与肝细胞癌肝切除术后早期复发的关联研究

Dose-response analysis of the associations between serum CXCL9 and FABP5 levels and early recurrence of hepatocellular carcinoma after hepatectomy

投稿时间：2026-06-17 修订日期：2026-10-08

DOI：

中文关键词: 肝细胞癌腹腔镜肝切除术早期复发剂量反应模型 CXC趋化因子配体9 脂肪酸结合蛋白5

英文关键词:hepatocellular carcinoma Laparoscopic hepatectomy Early recurrence Dose–response model C-X-C motif chemokine ligand 9 Fatty acid-binding protein 5

基金项目:

作者	单位	邮编
罗韬	中南大学湘雅医学院附属常德医院（常德市第一人民医院）	415000
陈志刚	中南大学湘雅医学院附属常德医院（常德市第一人民医院）
吴小龙	中南大学湘雅医学院附属常德医院（常德市第一人民医院）
杨浩洁	中南大学湘雅医学院附属常德医院（常德市第一人民医院）
武冲^*	中南大学湘雅医学院附属常德医院（常德市第一人民医院）	415000

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中文摘要:

[目的]探讨血清CXC趋化因子配体9（CXCL9）、脂肪酸结合蛋白5（FABP5）水平与肝细胞癌（HCC）肝切除术后早期复发的关系。[方法]收集2018年1月至2023年12月我院181例HCC患者临床资料进行回顾性分析，均行腹腔镜肝癌切除术，随访截至时间为2025年12月，所有患者均完成至少2年随访，以术后2年内复发定义为早期复发。采用酶联免疫吸附法测定血清CXCL9、FABP5，采用多因素Logistic回归分析术后早期复发相关因素，采用限制性立方样条模型（RCS）分析血清CXCL9、FABP5 水平与术后早期复发的剂量反应关系。[结果]181例HCC患者术后2年内54例早期复发。复发组断端切缘阳性、淋巴结转移率高于未复发组（P＜0.05），复发组术后1周、1个月AFP、CXCL9、FABP5水平分别为（237.79±55.42、222.56±34.45）ng/ml、（900.53±187.71、898.79±169.93）pg/ml、（12.85±1.83、11.71±1.52）ug/L，均高于未复发组（200.03±48.89、167.76±21.12）ng/ml、（820.20±171.22、700.04±157.73）pg/ml、（11.04±1.46、9.46±1.15）ug/L（P＜0.05）。单因素分析显示，断端切缘阳性、淋巴结转移、术后1个月AFP、CXCL9、FABP5均与术后早期复发存在相关性（均P＜0.05）；多因素分析显示，术后1个月 CXCL9（OR：1.514，95%CI：1.192～1.992）、FABP5（OR：1.633，95%CI：1.246～2.140）是术后早期复发的独立影响因素（均P＜0.05），而断端切缘阳性、淋巴结转移、术后1个月AFP不再表现为独立影响因素（均P＞0.05）。校正潜在混杂因素后，术后1个月血清CXCL9、FABP5 水平与术后早期复发关联强度呈现明显的非线性剂量反应关系（P＜0.05）。[结论]HCC患者术后1个月血清CXCL9、FABP5水平与肝切除术后早期复发呈J型曲线关系，可为后续精准预后分层与个体化诊疗提供参考信息。

英文摘要:

[Objective]To investigate the relationships between serum C-X-C motif chemokine ligand 9 (CXCL9) and fatty acid-binding protein 5 (FABP5) levels and early recurrence of hepatocellular carcinoma (HCC) following hepatectomy.[Methods]Clinical data of 181 patients with HCC who underwent laparoscopic hepatectomy at our hospital between January 2018 and December 2023 were retrospectively analyzed. The follow-up cutoff date was December 2025, and all patients completed a follow-up period of at least 2 years. Early recurrence was defined as tumor recurrence within 2 years after surgery. Serum CXCL9 and FABP5 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Multivariate Logistic regression was applied to identify factors associated with early postoperative recurrence. Restricted cubic spline (RCS) models were used to evaluate the dose-response relationships between serum CXCL9, FABP5 levels and early postoperative recurrence.[Results]Among the 181 included HCC patients, 54 developed early recurrence within 2 years after hepatectomy. The rates of positive surgical margin and lymph node metastasis were higher in the recurrence group than in the non-recurrence group (P < 0.05). The levels of AFP, CXCL9 and FABP5 at 1 week and 1 month after surgery in the recurrence group were (237.79 ± 55.42, 222.56 ± 34.45) ng/ml, (900.53 ± 187.71, 898.79 ± 169.93) pg/ml, and (12.85 ± 1.83, 11.71 ± 1.52) μg/L, respectively, which were significantly higher than those in the non-recurrence group [(200.03 ± 48.89, 167.76 ± 21.12) ng/ml, (820.20 ± 171.22, 700.04 ± 157.73) pg/ml, (11.04 ± 1.46, 9.46 ± 1.15) μg/L, all P < 0.05]. Univariate analysis demonstrated that positive surgical margin, lymph node metastasis, AFP, CXCL9 and FABP5 at 1 month after surgery were correlated with early postoperative recurrence (all P < 0.05). Multivariate Logistic regression showed that serum CXCL9 (OR = 1.514, 95%CI: 1.192–1.992) and FABP5 (OR = 1.633, 95%CI: 1.246–2.140) at 1 month after surgery were independent risk factors for early postoperative recurrence (all P < 0.05), whereas positive surgical margin, lymph node metastasis and AFP at 1 month after surgery were no longer independent correlates (all P > 0.05).After adjustment for potential confounding factors, serum CXCL9 and FABP5 levels at 1 month postoperatively exhibited a significant non-linear doseresponse relationship with early postoperative recurrence (P < 0.05).[Conclusion]Serum CXCL9 and FABP5 levels at 1 month postoperatively exhibited a J-shaped dose-response association with early recurrence after hepatectomy in patients with HCC. These biomarkers may facilitate precise prognostic stratification and individualized clinical management.

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