Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Hepatol Commun. 2024 Oct 3;8(10). doi: 10.1097/HC9.0000000000000548. eCollection 2024 Oct 1.
Transarterial chemoembolization (TACE) is the first-line treatment for patients with advanced HCC, but there are limited studies on the microenvironment alterations caused by TACE.
Six fresh HBV-related HCC specimens with or without TACE intervention were used to perform single-cell RNA sequencing. The 757 bulk samples from 3 large-scale multicenter cohorts were applied for comprehensive analysis. The biological functions of the biomarkers were further validated by phenotypic experiments.
Using single-cell RNA sequencing analysis, we delineated the global cell atlas of post-TACE and demonstrated elevated tumor heterogeneity and an enhanced proinflammatory microenvironment induced by TACE. Cell-cell communication analysis revealed that markedly elevated interactions between NABP1+ malignant hepatocytes, neutrophils, and CD8+ T cells after TACE might accelerate the shift from CD8+ effector memory T cells to CD8+ effector T cells. This result was substantiated by the developmental trajectory between the 2 and dramatically decreased resident scores along the pseudotemporal trajectory. Integrating bulk data, we further found that the increased estimated proportion of NABP1+ malignant hepatocytes was related to poor TACE response and dismal prognosis, and its biomarker role could be replaced by NABP1. In vitro, multiple biological experiments consistently verified that NABP1 knockdown significantly inhibited the proliferation and migration of HCC cells.
Based on our depicted global map of post-TACE, we confirmed that the enhanced interactions within the microenvironment after TACE may be the culprits for postoperative progression. NABP1 may become an attractive tool for the early identification of patients sensitive to first-line TACE in clinical practice.
经动脉化疗栓塞术（TACE）是治疗晚期 HCC 患者的一线治疗方法，但关于 TACE 引起的微环境改变的研究有限。
使用单细胞 RNA 测序分析对 6 例伴有或不伴有 TACE 干预的 HBV 相关 HCC 新鲜标本进行分析。对 3 个大型多中心队列的 757 个批量样本进行综合分析。通过表型实验进一步验证了生物标志物的生物学功能。
通过单细胞 RNA 测序分析，我们描绘了 TACE 后的全局细胞图谱，并证明 TACE 引起的肿瘤异质性和促炎微环境增强。细胞间通讯分析表明，TACE 后 NABP1+恶性肝细胞、中性粒细胞和 CD8+T 细胞之间的相互作用明显增加，可能加速 CD8+效应记忆 T 细胞向 CD8+效应 T 细胞的转变。这一结果通过 2 个之间的发育轨迹以及伪时间轨迹上的驻留评分明显降低得到证实。整合批量数据，我们进一步发现，NABP1+恶性肝细胞的估计比例增加与 TACE 反应不良和预后不良有关，其生物标志物作用可被 NABP1 取代。在体外，多项生物学实验一致证实，NABP1 敲低显著抑制 HCC 细胞的增殖和迁移。
基于我们描绘的 TACE 后全局图谱，我们证实 TACE 后微环境内增强的相互作用可能是术后进展的罪魁祸首。NABP1 可能成为临床实践中识别对一线 TACE 敏感患者的有吸引力的工具。
