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肿瘤微环境在肝细胞癌中的预后及预测意义

Prognostic and predictive significance of the tumor microenvironment in hepatocellular carcinoma.

作者信息

Liu Jibing, Kuang Shuwen, Zheng Yiling, Liu Mei, Wang Liming

机构信息

Department of Interventional Surgical Oncology, Cancer Hospital of Shandong Province, Shandong Academy of Medical Sciences, Jinan, Shandong, China.

Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Cancer Biomark. 2021;32(1):99-110. doi: 10.3233/CBM-203003.

DOI:10.3233/CBM-203003
PMID:34092607
Abstract

BACKGROUND

Identification of molecular markers that reflect the characteristics of the tumor microenvironment (TME) may be beneficial to predict the prognosis of post-operative hepatocellular carcinoma (HCC) patients.

OBJECTIVE AND METHODS

A total of 100 tissue samples from HCC patients were separately stained by immunohistochemistry to examine the expression levels of CD56, CD8α, CD68, FoxP3, CD31 and pan-Keratin. The prognostic values were analyzed by Cox regression and the Kaplan-Meier method.

RESULTS

Univariate and multivariate logistic analysis showed that FoxP3 was the independent factor associated with microvascular invasion (MVI), tumor size and envelop invasion; CD68 was associated with envelope invasion and AFP. Kaplan-Meier survival curves revealed that CD68 and FoxP3 expression were significantly associated with relapse free survival (RFS) of HCC patients (P< 0.05). The ROC curve indicated that the combination of tumor number, MVI present and CD68 expression yielded a ROC curve area of 82.3% (86.36% specificity, 68.75% sensitivity) to evaluate the prognosis of HCC patients, which was higher than the classifier established by the combination of tumor number and MVI (78.8% probability, 63.64% specificity and 85.42% sensitivity).

CONCLUSIONS

Our study indicated that CD68 and FoxP3 are associated with prognosis of HCC patients, and CD68 can be considered as a potential prognostic and predictive biomarker.

摘要

背景

识别反映肿瘤微环境(TME)特征的分子标志物可能有助于预测肝细胞癌(HCC)术后患者的预后。

目的与方法

对100例HCC患者的组织样本进行免疫组织化学染色,检测CD56、CD8α、CD68、FoxP3、CD31和泛角蛋白的表达水平。采用Cox回归和Kaplan-Meier法分析预后价值。

结果

单因素和多因素逻辑分析显示,FoxP3是与微血管侵犯(MVI)、肿瘤大小和包膜侵犯相关的独立因素;CD68与包膜侵犯和甲胎蛋白相关。Kaplan-Meier生存曲线显示,CD68和FoxP3表达与HCC患者的无复发生存期(RFS)显著相关(P<0.05)。ROC曲线表明,肿瘤数量、存在的MVI和CD68表达的组合产生的ROC曲线面积为82.3%(特异性86.36%,敏感性68.75%),用于评估HCC患者的预后,高于由肿瘤数量和MVI组合建立的分类器(概率78.8%,特异性63.64%,敏感性85.42%)。

结论

我们的研究表明,CD68和FoxP3与HCC患者的预后相关,且CD68可被视为一种潜在的预后和预测生物标志物。

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