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肝细胞癌根治性切除术后患者的新型免疫相关预后模型。

Novel immune-related prognostic models for patients with hepatocellular carcinoma after curative resection.

作者信息

Cao Mingnan, Pan Chen, Zhao Zhigang, Ye Sisi, Bai Li, Zhang Tingting

机构信息

Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.

Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.

出版信息

Hepatol Int. 2025 May 15. doi: 10.1007/s12072-025-10839-x.

Abstract

BACKGROUND

The patterns of postoperative recurrence vary among hepatocellular carcinoma (HCC) patients and infiltration of immune cells is correlated with patients prognosis. The present study aimed to develop and assess novel nomogram models for postsurgical recurrence and survival in HCC patients by combination of immune cell scores and clinicopathological features.

METHODS

A total of 233 patients with curative hepatic resection and complete clinicopathologic information were enrolled. The infiltration of CD8 + T lymphocytes, CD15 + neutrophils and CD68 + macrophages in the tumor microenvironment was assessed by immunohistochemistry in tissue microarray. Two prognostic nomogram models for disease-free survival (DFS) and overall survival (OS) were developed and multi-dimensionally evaluated to predict postsurgical HCC outcomes.

RESULTS

The DFS nomogram was developed using AFP, GGT, tumor differentiation, Ki-67, and the densities of intratumoral CD15 + neutrophils and CD68 + macrophages. The OS nomogram was established based on gender, AFP, tumor differentiation, number of tumor nodules, microvascular vascular tumor thrombus (MVTT), Ki-67, microvessel density (MVD), the densities of intratumoral CD15 + neutrophils and CD68 + macrophages. The C-indexes for the DFS and OS nomogram were 0.708 (95% CI, 0.675-0.741) and 0.723 (95% CI, 0.688 to 0.758), respectively. The AUC values of the models for 1-, 2- or 5-year DFS were 0.832, 0.807 and 0.783, and for 1-, 2- or 5-year OS were 0.745, 0.794 and 0.842.

CONCLUSION

The present study proposed two nomogram models integrating infiltrating immune cells with clinicopathological risks and showed relatively good predictive performance of recurrence and survival, which may be beneficial to the clinical practice of HCC stratification. Further multicenter studies are needed to assess its general applicability.

摘要

背景

肝细胞癌(HCC)患者术后复发模式各异,免疫细胞浸润与患者预后相关。本研究旨在通过结合免疫细胞评分和临床病理特征,开发并评估用于预测HCC患者术后复发和生存的新型列线图模型。

方法

共纳入233例行根治性肝切除术且具备完整临床病理信息的患者。通过组织芯片免疫组化评估肿瘤微环境中CD8 + T淋巴细胞、CD15 + 中性粒细胞和CD68 + 巨噬细胞的浸润情况。开发了两个用于无病生存期(DFS)和总生存期(OS)的预后列线图模型,并进行多维度评估以预测HCC术后结局。

结果

DFS列线图模型采用甲胎蛋白(AFP)、γ-谷氨酰转肽酶(GGT)、肿瘤分化程度、Ki-67以及瘤内CD15 + 中性粒细胞和CD68 + 巨噬细胞密度构建。OS列线图基于性别、AFP、肿瘤分化程度、肿瘤结节数量、微血管肿瘤血栓(MVTT)、Ki-67、微血管密度(MVD)、瘤内CD15 + 中性粒细胞和CD68 + 巨噬细胞密度建立。DFS和OS列线图的C指数分别为0.708(95%CI,0.675 - 0.741)和0.723(95%CI,0.688至0.758)。该模型预测1年、2年或5年DFS的AUC值分别为0.832、0.807和0.783,预测1年、2年或5年OS的AUC值分别为0.745、0.794和0.842。

结论

本研究提出了两个将浸润免疫细胞与临床病理风险相结合的列线图模型,其对复发和生存具有相对良好的预测性能,可能有助于HCC分层的临床实践。需要进一步开展多中心研究以评估其普遍适用性。

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