• Lin Liu, Siyu Hao, Shuang Gou, Xiaolong Tang, Yao Zhang, Dan Cai, Mintao Xiao, Xinyi Zhang, Duoli Zhang, Jing Shen, Yan Li, Yu Chen, Yueshui Zhao, Shuai Deng, Xu Wu, Mingxing Li, Zhuo Zhang, Zhangang Xiao, and Fukuan Du.
• Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Sichuan Luzhou 646000, China; Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Sichuan Luzhou, 646000, China; South Sichuan Institute of Translational Medicine, Sichuan Luzhou 646000, China.
• Transl Res. 2024 Oct 1; 272: 194019-40.

AbstractHCC is a malignancy characterized by high incidence and mortality rates. Traditional classifications of HCC primarily rely on tumor morphology, phenotype, and multicellular molecular levels, which may not accurately capture the cellular heterogeneity within the tumor. This study integrates scRNA-seq and bulk RNA-seq to spotlight HP as a critical gene within a subgroup of HCC malignant cells. HP is highly expressed in HCC malignant cells and lowly expressed in T cells. Within malignant cells, elevated HP expression interacts with C3, promoting Th1-type responses via the C3/C3AR1 axis. In T cells, down-regulating HP expression favors the expression of Th1 cell-associated marker genes, potentially enhancing Th1-type responses. Consequently, we developed a "HP-promoted Th1 response reclassification" gene set, correlating higher activity scores with improved survival rates in HCC patients. Additionally, four predictive models for neoadjuvant treatment based on HP and C3 expression were established: 1) Low HP and C3 expression with high Th2 cell infiltration; 2) High HP and low C3 expression with high Th2 cell infiltration; 3) High HP and C3 expression with high Th1 cell infiltration; 4) Low HP and high C3 expression with high Th1 cell infiltration. In conclusion, the HP gene selected from the HCC malignant cell subgroup (Malignant_Sub 6) might serve as a potential ally against the tumor by promoting Th1-type immune responses. The establishment of the "HP-promoted Th1 response reclassification" gene set offers predictive insights for HCC patient survival prognosis and neoadjuvant treatment efficacy, providing directions for clinical treatments.Copyright © 2024 Elsevier Inc. All rights reserved.

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