Identification of PANoptosis-Based Prognostic Signature for Predicting Efficacy of Immunotherapy and Chemotherapy in Hepatocellular Carcinoma.

IF 1.4 4区生物学 Q4 GENETICS & HEREDITY Genetics research Pub Date : 2023-01-01 DOI:10.1155/2023/6879022

Xiaofeng Xiong, Qianben Song, Mengjia Jing, Wei Yan

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引用次数: 2

Abstract

Background: PANoptosis has been a research hotspot, but the role of PANoptosis in hepatocellular carcinoma (HCC) remains widely unknown. Drug resistance and low response rate are the main limitations of chemotherapy and immunotherapy in HCC. Thus, construction of a prognostic signature to predict prognosis and recognize ideal patients for corresponding chemotherapy and immunotherapy is necessary.

Method: The mRNA expression data of HCC patients was collected from TCGA database. Through LASSO and Cox regression, we developed a prognostic signature based on PANoptosis-related genes. KM analysis and ROC curve were implemented to evaluate the prognostic efficacy of this signature, and ICGC and GEO database were used as external validation cohorts. The immune cell infiltration, immune status, and IC50 of chemotherapeutic drugs were compared among different risk subgroups. The relationships between the signature and the efficacy of ICI therapy, sorafenib treatment, and transcatheter arterial chemoembolization (TACE) therapy were investigated.

Result: A 3-gene prognostic signature was constructed which divided the patients into low- and high-risk subgroups. Low-risk patients had better prognosis, and the risk score was proved to be an independent predictor of overall survival (OS), which had a well predictive effect. Patients in high-risk population had more immunosuppressive cells (Tregs, M0 macrophages, and MDSCs), higher TIDE score and TP53 mutation rate, and elevated activity of base excision repair (BER) pathways. Patients with low risk benefited more from ICI, TACE, and sorafenib therapy. The predictive value of the risk score was comparable with TIDE and MSI for OS under ICI therapy. The risk score could be a biomarker to predict the response to ICI, TACE, and sorafenib therapy.

Conclusion: The novel signature based on PANoptosis is a promising biomarker to distinguish the prognosis predict the benefit of ICI, TACE, and sorafenib therapy, and forecast the response to them.

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基于panoposis的肝细胞癌预测免疫治疗和化疗疗效的预后特征的鉴定。

背景:PANoptosis一直是研究热点，但PANoptosis在肝细胞癌(HCC)中的作用尚不清楚。耐药和低反应率是肝癌化疗和免疫治疗的主要限制。因此，有必要建立预后标记来预测预后并识别理想的患者进行相应的化疗和免疫治疗。方法:从TCGA数据库中收集肝癌患者mRNA表达数据。通过LASSO和Cox回归，我们建立了一个基于panoptoses相关基因的预后标志。采用KM分析和ROC曲线评价该特征的预后效果，并采用ICGC和GEO数据库作为外部验证队列。比较不同危险亚组化疗药物的免疫细胞浸润、免疫状态及IC50。研究了ICI治疗、索拉非尼治疗和经导管动脉化疗栓塞(TACE)治疗的特征与疗效的关系。结果:构建了3基因预后标记，将患者分为低危亚组和高危亚组。低危患者预后较好，风险评分被证明是总生存(OS)的独立预测指标，具有较好的预测作用。高危人群患者免疫抑制细胞(Tregs、M0巨噬细胞和MDSCs)增多，TIDE评分和TP53突变率升高，碱基切除修复(BER)通路活性升高。低风险患者从ICI、TACE和索拉非尼治疗中获益更多。ICI治疗下OS的风险评分预测值与TIDE和MSI相当。风险评分可以作为预测ICI、TACE和索拉非尼治疗反应的生物标志物。结论:基于PANoptosis的新标记是一种很有前景的生物标志物，可用于区分预后、预测ICI、TACE和索拉非尼治疗的获益以及预测对这些治疗的反应。

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来源期刊

Genetics research 生物-遗传学

自引率

6.70%

发文量

审稿时长

>12 weeks

期刊介绍： Genetics Research is a key forum for original research on all aspects of human and animal genetics, reporting key findings on genomes, genes, mutations and molecular interactions, extending out to developmental, evolutionary, and population genetics as well as ethical, legal and social aspects. Our aim is to lead to a better understanding of genetic processes in health and disease. The journal focuses on the use of new technologies, such as next generation sequencing together with bioinformatics analysis, to produce increasingly detailed views of how genes function in tissues and how these genes perform, individually or collectively, in normal development and disease aetiology. The journal publishes original work, review articles, short papers, computational studies, and novel methods and techniques in research covering humans and well-established genetic organisms. Key subject areas include medical genetics, genomics, human evolutionary and population genetics, bioinformatics, genetics of complex traits, molecular and developmental genetics, Evo-Devo, quantitative and statistical genetics, behavioural genetics and environmental genetics. The breadth and quality of research make the journal an invaluable resource for medical geneticists, molecular biologists, bioinformaticians and researchers involved in genetic basis of diseases, evolutionary and developmental studies.