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构建一种与失巢凋亡相关的预后特征以预测肝细胞癌的免疫治疗反应和预后。

Construction of an anoikis‒related prognostic signature to predict immunotherapeutic response and prognosis in hepatocellular carcinoma.

作者信息

Xiong Chen, Pan Guoqiang, Wang Hanchao, Meng Guangxiao, Yan Lunjie, Li Ruizhe, Yan Yuchuan, Yang Yafei, Zhang Xiao, Yang Chuncheng, Dong Zhaoru, Li Tao

机构信息

Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250100, China.

Institute for Financial Studies, Shandong University, Jinan, 250100, China.

出版信息

J Cancer Res Clin Oncol. 2023 Dec;149(18):16869-16884. doi: 10.1007/s00432-023-05428-0. Epub 2023 Sep 22.

Abstract

PURPOSE

Anoikis resistance is an important inducer of tumor metastasis. The role of anoikis-related genes (ARGs) in hepatocellular carcinoma (HCC) remains unclear.

METHODS

A list of ARGs was obtained and regression analysis was employed to assemble an anoikis-related prognostic signature and risk score formula from mRNA data and clinical prognostic data downloaded from The Cancer Genome Atlas database. Quantitative real-time PCR (qRT-PCR) was performed on clinical samples to validate the selected ARGs expressions. Kaplan‒Meier curves, ROC curves, and Cox regression analyses were used to demonstrated the prognostic value of this signature. Biological functional enrichment analysis and immune infiltration analysis were utilized to analyze the differences in potential biological functions, immune cell infiltration, immune functions, and immunotherapeutic responses.

RESULTS

A prognostic signature based on 6 ARGs and corresponding prognostic nomogram were established. Our qRT-PCR results showed a higher expression of 6 ARGs in HCC tissues (p value < 0.05). Kaplan‒Meier curves, ROC curves, and Cox regression analyses demonstrated good prognostic value of the signature in HCC (p value < 0.05). Significant differences between the enriched biological functions and immune landscapes of patients in different risk groups were discovered (p value < 0.05). In addition, patients with higher risk scores possibly had poor therapeutic response to transhepatic arterial chemotherapy and embolization or sorafenib, but their responses to immunotherapy might be more effective.

CONCLUSION

A successful anoikis-related prognostic signature and corresponding clinical nomogram were established, which might facilitate better predictions of prognosis and therapeutic responses for HCC patients.

摘要

目的

失巢凋亡抗性是肿瘤转移的重要诱导因素。失巢凋亡相关基因(ARGs)在肝细胞癌(HCC)中的作用仍不清楚。

方法

获取ARGs列表,并采用回归分析从从癌症基因组图谱数据库下载的mRNA数据和临床预后数据中构建失巢凋亡相关的预后特征和风险评分公式。对临床样本进行定量实时PCR(qRT-PCR)以验证所选ARGs的表达。使用Kaplan-Meier曲线、ROC曲线和Cox回归分析来证明该特征的预后价值。利用生物功能富集分析和免疫浸润分析来分析潜在生物学功能、免疫细胞浸润、免疫功能和免疫治疗反应的差异。

结果

建立了基于6个ARGs的预后特征和相应的预后列线图。我们的qRT-PCR结果显示6个ARGs在HCC组织中的表达较高(p值<0.05)。Kaplan-Meier曲线、ROC曲线和Cox回归分析表明该特征在HCC中具有良好的预后价值(p值<0.05)。发现不同风险组患者的富集生物学功能和免疫景观之间存在显著差异(p值<0.05)。此外,风险评分较高的患者可能对经肝动脉化疗栓塞或索拉非尼的治疗反应较差,但其对免疫治疗的反应可能更有效。

结论

成功建立了与失巢凋亡相关的预后特征和相应的临床列线图,这可能有助于更好地预测HCC患者的预后和治疗反应。

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