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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1498528
This article is part of the Research Topic Advancements in the Heterogeneity of Sex for Tumors View all 8 articles

ABCA1 promote tumor environment heterogeneity via epithelial mesenchymal transition in Huh7 and HepG2 liver cancer cell

Provisionally accepted
Dinglai Yu Dinglai Yu 1Fang Guo Fang Guo 2Qiyu Zhang Qiyu Zhang 3Huajun Yu Huajun Yu 3Wenmin Wang Wenmin Wang 4Yunzhi Chen Yunzhi Chen 3*
  • 1 Department of Hepatobiliary Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China
  • 2 Department of Obstetrics and Gynecology, Wenzhou People's Hospital, wenzhou, China
  • 3 Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital of Wenzhou Medical University, wenzhou, China
  • 4 The Yangtze River Delta Biological Medicine Research and Development Center of Zhejiang Province, Yangtze Delta Region Institution of Tsinghua University, Hangzhou, Zhejiang, 314006, China, Hangzhou, China

The final, formatted version of the article will be published soon.

    In this study, we delve into the intrinsic mechanisms of cell communication in hepatocellular carcinoma (HCC). Initially, employing single-cell sequencing, we analyze multiple malignant cell subpopulations and cancer-associated fibroblast (CAF) subpopulations, revealing their interplay through receptor-ligand interactions, with a particular focus on SPP1. Subsequently, employing unsupervised clustering analysis, we delineate two clusters, C1 and C2, and compare their infiltration characteristics using various tools and metrics, uncovering heightened cytotoxicity and overall 2 invasion abundance in C1. Furthermore, our gene risk scoring model indicates heightened activity of the immune therapeutic pathway in C1. Lastly, employing a formulated scoring system, we stratify patients into high and low-risk groups, revealing notably poorer outcomes in the high-risk cohort on Kaplan-Meier curves. Risk scores exhibit a negative correlation with model genes and immune cell infiltration scores, indicating poor prognosis in the high-risk group. Further characterization elucidates the regulatory landscape of the high and low-risk groups across various signaling pathways. In addition, we used wet lab experiments to prove that ABCA1 plays a pro-oncogenic role in hepatocellular carcinoma cells by promoting proliferation, invasion, migration, and reducing apoptosis. In summary, these findings provide crucial insights, offering valuable clues and references for understanding HCC pathogenesis and patient prognosis.

    Keywords: Hepatocellular Carcinoma, single-cell sequencing, Tumor Microenvironment, risk stratification, Immune Therapeutic Pathway

    Received: 19 Sep 2024; Accepted: 03 Dec 2024.

    Copyright: © 2024 Yu, Guo, Zhang, Yu, Wang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Yunzhi Chen, Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital of Wenzhou Medical University, wenzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.