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中华肝脏外科手术学电子杂志

中华肝脏外科手术学电子杂志 ›› 2026, Vol. 15 ›› Issue (03) : 346 -354. doi: 10.3877/cma.j.issn.2095-3232.2026.03.008

临床研究

肿瘤包绕型血管在接受仑伐替尼治疗肝癌患者生存预后中的预测价值
李旭柯, 熊培尧, 杨子良, 敖玉凤, 徐立†()   
  1. 510060　广州，中山大学肿瘤防治中心肝脏外科
  • 收稿日期:2025-11-14 出版日期:2026-06-10
  • 通信作者: 徐立
  • 基金资助:
    国家自然科学基金(81772589)

Predictive value of vessels encapsulating tumor clusters in survival and prognosis of hepatocellular carcinoma patients treated with lenvatinib

Xuke Li, Peiyao Xiong, Ziliang Yang, Yufeng Ao, Li Xu†()   

  1. Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
  • Received:2025-11-14 Published:2026-06-10
  • Corresponding author: Li Xu
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引用本文：

李旭柯, 熊培尧, 杨子良, 敖玉凤, 徐立. 肿瘤包绕型血管在接受仑伐替尼治疗肝癌患者生存预后中的预测价值[J/OL]. 中华肝脏外科手术学电子杂志, 2026, 15(03): 346-354.

Xuke Li, Peiyao Xiong, Ziliang Yang, Yufeng Ao, Li Xu. Predictive value of vessels encapsulating tumor clusters in survival and prognosis of hepatocellular carcinoma patients treated with lenvatinib[J/OL]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(03): 346-354.

目的

探讨肿瘤包绕型血管（VETC）在接受仑伐替尼治疗肝细胞癌（肝癌）患者生存预后中的预测价值。

方法

回顾性分析2018年7月至2020年1月于中山大学附属肿瘤医院接受仑伐替尼单药治疗的101例肝癌患者临床及病理资料。其中男88例，女13例；年龄19~78岁，中位年龄51岁。符合医学伦理学规定，并豁免知情同意书。采用CD34免疫组化染色评估VETC状态，据此分为VETC阳性组和VETC阴性组。采用1∶2倾向性评分匹配（PSM）平衡两组基线特征。主要研究终点为无进展生存期（PFS），次要研究终点包括总生存期（OS）、肝外PFS和肝内PFS。生存分析采用Kaplan-Meier法和Log-rank检验。生存预后影响因素分析采用Cox比例风险回归模型。

结果

PSM前VETC阳性组33例，VETC阴性组68例，VETC阳性组门脉癌栓发生率21%（7/33），明显低于VETC阴性组的50%（34/68）（χ2=7.635，P=0.006）。PSM后VETC阳性组33例，VETC阴性组48例，VETC阳性组与VETC阴性组中位PFS分别为5.0、7.6个月，差异有统计学意义（HR=0.60，P=0.037），而两组OS比较差异无统计学意义（HR=1.00，P=0.990）。VETC阳性组肝外PFS明显差于VETC阴性组（HR=0.46，P=0.004），而两组的肝内PFS差异无统计学意义（HR=0.81，P=0.475）。Cox多因素回归分析显示，仑伐替尼单药进展后接受后续系统治疗是OS的独立保护因素（HR=0.50，95%CI：0.30~0.84；P=0.009）。而VETC阳性（HR=1.74，95%CI：1.09~2.80）、远处转移（HR=1.83，95%CI：1.09~3.09）和AFP≥400 μg/L（HR=2.07，95%CI：1.30~3.31）是PFS的独立危险因素（P<0.05）；VETC阳性（HR=2.47，95%CI：1.40~4.35）、远处转移（HR=2.03，95%CI：1.09~3.81）和 AFP≥400 μg/L（HR=2.10，95%CI：1.21~3.64）亦是肝外PFS的独立危险因素（P<0.05）。

结论

VETC阳性是接受仑伐替尼治疗的肝癌患者PFS及肝外PFS的独立危险因素，VETC阳性预示更高的肝外进展风险和更短PFS。

关键词: 癌，肝细胞, 肿瘤包绕型血管, 仑伐替尼, 预后
Objective

To evaluate the predictive value of vessels encapsulating tumor clusters (VETC) in the survival and prognosis of hepatocellular carcinoma (HCC) patients treated with lenvatinib.

Methods

Clinicopathological data of 101 patients with HCC treated with lenvatinib alone in Sun Yat-sen University Cancer Center from July 2018 to January 2020 were retrospectively analyzed. Among them, 88 patients were male and 13 female, aged from 19 to 78 years, with a median age of 51 years. Exemption from the informed consents of all patients was obtained and the local ethical committee approval was received. The status of VETC was evaluated by CD34 immunohistochemical staining. All patients were divided into the VETC positive and negative groups. Baseline characteristics between two groups were balanced by 1:2 propensity score matching (PSM). The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), extrahepatic and intrahepatic PFS. Survival analysis was performed by Kaplan-Meier method and Log-rank test. The influencing factors of survival and prognosis were identified by Cox proportional hazards regression model.

Results

Before PSM, there were 33 patients in the VETC positive group and 68 in the VETC negative group. The incidence of portal vein tumor thrombus in the VETC positive group was 21%(7/33), significantly lower than 50%(34/68) in the VETC negative group (χ2=7.635, P=0.006). After PSM, there were 33 patients in the VETC positive group and 48 in the VETC negative group. The median PFS in the VETC positive and negative groups was 5.0 and 7.6 months, and the difference was statistically significant (HR=0.60, P=0.037). However, no statistical difference was observed in OS between two groups (HR=1.00, P=0.990). The extrahepatic PFS in the VETC positive group was significantly shorter than that in the VETC negative group (HR=0.46, P=0.004), but no significant difference was found in intrahepatic PFS between two groups (HR=0.81, P=0.475). Multivariate Cox regression analysis showed that receiving systematic therapy after the progression post-lenvatinib treatment alone was the independent protective factor of OS (HR=0.50, 95%CI: 0.30-0.84; P=0.009). However, VETC positivity (HR=1.74, 95%CI: 1.09-2.80), distant metastasis (HR=1.83, 95%CI: 1.09-3.09) and AFP≥400 μg/L (HR=2.07, 95%CI: 1.30-3.31) were the independent protective factors of PFS (all P<0.05). VETC positivity (HR=2.47, 95%CI: 1.40-4.35), distant metastasis (HR=2.03, 95%CI: 1.09-3.81) and AFP≥400 μg/L (HR=2.10, 95%CI: 1.21-3.64) were the independent risk factors of extrahepatic PFS (all P<0.05).

Conclusions

VETC positivity is the independent risk factor of PFS and extrahepatic PFS in HCC patients treated with lenvatinib. VETC positivity indicates a higher risk of extrahepatic progression and shorter PFS.

Key words: Carcinoma,hepatocellular, Vessels encapsulating tumor clusters, Lenvatinib, Prognosis
图1 肝癌组织CD34染色观察两种不同的血管模式（免疫组化法，×100） 注：a为VETC阳性，形成蛛网状结构并包裹肿瘤细胞簇的血管（箭头所示）；b为经典毛细血管；VETC为肿瘤包绕型血管，比例尺为100 μm
表1 PSM后两组肝癌患者基线特征
临床特征 VETC阳性 VETC阴性 统计值 P值
年龄[岁, M(Q1, Q3)] 50(40, 55) 54(42, 60) Z=-1.384 0.166
性别(例, 男/女) 30/3 40/8 χ2=0.420 0.517
HBsAg阳性(例) 30 41 χ2=0.156 0.693
抗-HCV阳性(例) 0 1 - >0.999
ECOG-PS评分0级(例) 5 9 χ2=0.177 0.674
肿瘤单发(例) 3 9 χ2=0.782 0.377
肿瘤最大径[cm, M(Q1, Q3)] 5.4(2.5, 9.8) 6.8 (3.8, 13.0) Z=-0.894 0.371
门脉癌栓(例) 7 14 χ2=0.644 0.422
区域淋巴结转移(例) 5 11 χ2=0.744 0.388
远处转移(例) 19 27 χ2=0.014 0.906
BCLC分期 B/C期(例) 31 46 - >0.999
CNLC分期Ⅱ/Ⅲ(例) 31 46 - >0.999
AFP≥400 μg/L(例) 18 20 χ2=1.302 0.254
PIVKA-Ⅱ≥40 mAU/ ml(例) 27 41 χ2=0.188 0.665
ALT[U/L, M(Q1, Q3)] 47(33, 81) 35(24, 61) Z=1.730 0.084
AST[U/L, M(Q1, Q3)] 42(35, 76) 47(31, 82) Z=0.159 0.874
TB[mol/L, M(Q1, Q3)] 13(12, 19) 13(10, 17) Z=0.952 0.341
ALB[g/L, M(Q1, Q3)] 44(40, 47) 43(38, 45) Z=1.038 0.299
ALBI评分1分(例) 26 32 χ2=1.413 0.235
PT[s, M(Q1, Q3)] 12.3 (11.6, 12.9) 12.2 (11.5, 13.2) Z=-0.115 0.908
Child-Pugh分级A级(例) 32 47 - >0.999
后续系统治疗(例) 23 36 χ2=0.278 0.598
后续局部治疗(例) 19 22 χ2=1.079 0.299
图2 PSM后VETC阳性组与VETC阴性组肝癌患者Kaplan-Meier生存曲线分析 注：VETC为肿瘤包绕型血管，PSM为倾向性评分匹配
表2 肝癌患者PFS和肝外PFS的Cox单因素和多因素回归分析
变量 PFS 肝外PFS
单因素Cox回归 多因素Cox回归 单因素Cox回归 多因素Cox回归
HR (95%CI) P值 HR (95%CI) P值 HR (95%CI) P值 HR (95%CI) P值
VETC阳性 1.66 (1.04~2.62) 0.032 1.74 (1.09~2.80) 0.021 2.21 (1.34~3.65) 0.002 2.47 (1.40~4.35) 0.002
年龄 0.98 (0.96~1.00) 0.078 0.99 (0.98~1.01) 0.524 0.97 (0.94~0.99) 0.002 0.98 (0.96~1.00) 0.087
ECOG-PS评分1级 1.70 (0.92~3.16) 0.092 1.21 (0.59~2.48) 0.610 2.27 (1.03~4.99) 0.042 1.38 (0.56~3.44) 0.487
区域淋巴结转移 1.38 (0.83~2.29) 0.213 / / 1.61 (0.92~2.81) 0.094 1.31 (0.69~2.46) 0.408
远处转移 1.79 (1.15~2.81) 0.011 1.83 (1.09~3.09) 0.023 2.19 (1.31~3.68) 0.003 2.03 (1.09~3.81) 0.026
AFP≥400 μg/L 2.08 (1.34~3.20) 0.001 2.07 (1.30~3.31) 0.002 2.34 (1.42~3.85) 0.001 2.10 (1.21~3.64) 0.008
图3 PSM后两组患者肝外PFS的Kaplan-Meier生存分析 注：a为肝外肺转移患者生存曲线，b为非肺转移患者生存曲线；VETC为肿瘤包绕型血管，PSM为倾向性评分匹配
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