Enhanced interactions within microenvironment accelerates dismal prognosis in HBV-related HCC after TACE.

IF 5.6 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Hepatology Communications Pub Date : 2024-10-03 eCollection Date: 2024-10-01 DOI:10.1097/HC9.0000000000000548
Libo Wang, Jiahui Cao, Zaoqu Liu, Shitao Wu, Yin Liu, Ruopeng Liang, Rongtao Zhu, Weijie Wang, Jian Li, Yuling Sun
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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

微环境中相互作用的增强加速了 TACE 后 HBV 相关 HCC 的不良预后。
背景:经动脉化疗栓塞术(TACE)是晚期HCC患者的一线治疗方法,但有关TACE引起的微环境改变的研究却十分有限:经动脉化疗栓塞术(TACE)是晚期HCC患者的一线治疗方法,但有关TACE引起的微环境改变的研究十分有限:方法:采用6份有或没有TACE干预的新鲜HBV相关HCC标本进行单细胞RNA测序。对来自 3 个大型多中心队列的 757 份批量样本进行了综合分析。通过表型实验进一步验证了生物标志物的生物学功能:利用单细胞 RNA 测序分析,我们绘制了 TACE 后的全球细胞图谱,并证明了 TACE 诱导的肿瘤异质性升高和促炎症微环境增强。细胞-细胞通讯分析表明,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强,这可能会加速 CD8+ 效应记忆 T 细胞向 CD8+ 效应 T 细胞的转变。二者之间的发展轨迹和沿假时空轨迹急剧下降的常驻评分证实了这一结果。综合大量数据,我们进一步发现,NABP1+恶性肝细胞估计比例的增加与 TACE 反应差和预后不良有关,其生物标志物作用可由 NABP1 替代。在体外,多种生物学实验一致验证了敲除 NABP1 能显著抑制 HCC 细胞的增殖和迁移:根据我们描绘的 TACE 术后全局图,我们证实 TACE 术后微环境中增强的相互作用可能是导致术后进展的罪魁祸首。在临床实践中,NABP1 可能成为早期识别对一线 TACE 敏感的患者的一种有吸引力的工具。
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来源期刊
Hepatology Communications
Hepatology Communications GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
8.00
自引率
2.00%
发文量
248
审稿时长
8 weeks
期刊介绍: Hepatology Communications is a peer-reviewed, online-only, open access journal for fast dissemination of high quality basic, translational, and clinical research in hepatology. Hepatology Communications maintains high standard and rigorous peer review. Because of its open access nature, authors retain the copyright to their works, all articles are immediately available and free to read and share, and it is fully compliant with funder and institutional mandates. The journal is committed to fast publication and author satisfaction. ​
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