Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang Province, Hangzhou, 310003, China.
Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Zhejiang Province, Hangzhou, 310003, China.
J Cancer Res Clin Oncol. 2023 Dec;149(18):16261-16277. doi: 10.1007/s00432-023-05370-1. Epub 2023 Sep 12.
Immunogenic cell death (ICD) has emerged as a promising strategy to activate the adaptive immune response, modulate the tumor microenvironment (TME) and enhance the efficacy of immune therapy. However, the relationship between ICD and TME reprogramming in hepatocellular carcinoma (HCC) remains poorly understood.
Transcriptional profiles and clinical spectrum of 486 HCC patients were obtained from TCGA and GEO databases. We utilized consensus clustering analysis to construct two distinct molecular subtypes and established an ICD-based scoring system (named ICD score) via WGCNA and LASSO Cox regression to predict the prognosis of the HCC cohort. Then we employed CIBERSORT and ESTIMATE methods to analyze the immune landscape of ICD score in HCC. Subsequently, the immunophenoscore (IPS) and tumor immune dysfunction and rejection (TIDE) analyses were performed to determine whether the ICD score could influence the immune therapeutic effect. Based on the ICD scoring system, a novel nomogram was generated to provide a numerical probability of HCC patients' overall survival (OS).
We identified two independent ICD clusters (cluster A/B), and cluster B possessed a worse prognosis and higher immune cell infiltration. Using ICD scoring system, the HCC patients were divided into high- and low-ICD-score groups. Through integrative analyses, the high-ICD cohort owned advanced TNM stage, high pathologic grade and increased suppressive immune cell enrichment. We developed a nomogram containing the ICD score, demonstrating a high predictive accuracy with a C-index of 0.703. We further discovered that PSMD2 and PSMD14 could serve as ICD-associated prognostic biomarkers and therapeutic targets in HCC.
The ICD score exhibits a high degree of reliability for predicting prognosis and may provide valuable guidance for the selection of immunotherapy for HCC patients. This novel scoring system enables the estimation of clinical immunotherapy response for HCC patients, offering new opportunities for personalized immunotherapy.
免疫原性细胞死亡（ICD）已成为一种有前途的策略，可以激活适应性免疫反应、调节肿瘤微环境（TME）并增强免疫治疗的疗效。然而，肝细胞癌（HCC）中 ICD 与 TME 重编程之间的关系仍知之甚少。
从 TCGA 和 GEO 数据库中获取 486 例 HCC 患者的转录谱和临床谱。我们利用共识聚类分析构建了两个不同的分子亚型，并通过 WGCNA 和 LASSO Cox 回归建立了基于 ICD 的评分系统（命名为 ICD 评分），以预测 HCC 队列的预后。然后，我们采用 CIBERSORT 和 ESTIMATE 方法分析 HCC 中 ICD 评分的免疫景观。随后，进行免疫表型评分（IPS）和肿瘤免疫功能障碍和排斥（TIDE）分析，以确定 ICD 评分是否会影响免疫治疗效果。基于 ICD 评分系统，生成了一个新的列线图，以提供 HCC 患者总生存率（OS）的数值概率。
我们确定了两个独立的 ICD 簇（簇 A/B），簇 B 具有更差的预后和更高的免疫细胞浸润。使用 ICD 评分系统，将 HCC 患者分为高 ICD 评分组和低 ICD 评分组。通过综合分析，高 ICD 组具有更先进的 TNM 分期、更高的病理分级和增加的抑制性免疫细胞富集。我们开发了一个包含 ICD 评分的列线图，其 C 指数为 0.703，具有较高的预测准确性。我们进一步发现 PSMD2 和 PSMD14 可以作为 HCC 中与 ICD 相关的预后生物标志物和治疗靶点。
ICD 评分在预测预后方面具有高度可靠性，可为 HCC 患者的免疫治疗选择提供有价值的指导。这个新的评分系统可以估计 HCC 患者的临床免疫治疗反应，为个性化免疫治疗提供新的机会。
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