2. Academic Validation
  3. Impact of apolipoprotein A1 on tumor immune microenvironment, clinical prognosis and genomic landscape in hepatocellular carcinoma

Impact of apolipoprotein A1 on tumor immune microenvironment, clinical prognosis and genomic landscape in hepatocellular carcinoma

  • Precis Clin Med. 2023 Sep 2;6(3):pbad021. doi: 10.1093/pcmedi/pbad021.
Ying Wang 1 2 3,  Shipeng Chen 4,  Xiao Xiao 1,  Fan Yang 5,  Jinhan Wang 6,  Hui Zong 3 7,  Yuzhen Gao 8,  Chenjun Huang 1,  Xuewen Xu 1,  Meng Fang 2,  Xiaoyan Zhang 3,  Chunfang Gao 1
Affiliations

Affiliations

  • 1 Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
  • 2 Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China.
  • 3 Research Center for Translational Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
  • 4 Department of Medical Microbiology and Infection Prevention, Tumor Virology and Cancer Immunotherapy, University Medical Center Groningen, University of Groningen, Groningen 9712 CP, The Netherlands.
  • 5 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China.
  • 6 Department of Hepatobiliary and Pancreatic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai200120, China.
  • 7 Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 8 Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
PMID: 38025972 DOI: 10.1093/pcmedi/pbad021
Abstract

Background: Current knowledge on Apolipoprotein A1 (APOA1) in hepatocellular carcinoma (HCC) is fragmented and even contradictory. Multi-dimensional analyses are required to comprehensively elucidate its value and underlying mechanism.

Methods: We collected 49 RNA-seq datasets, 40 cell line types data and 70 scRNA pan-cancer datasets public available, including 17 HCC datasets (1754 tumor samples), and enrolled 73 pairs of HCC tissue and 516 blood samples independently from our clinics. APOA1 impacting on the HCC tumor microenvironment (TME) was analyzed using intensive data mining. Methylation Sequencing, flow cytometry, quantitative PCR, western blot, immunohistochemistry and clinical chemistry assays were conducted for wet experimental investigation.

Results: The APOA1 ontology fingerprint indicated that it played various crucial biological roles in HCC, primarily involved in Cholesterol efflux. Consistent findings at histology, serology, and clinical follow-up revealed that high APOA1 was a good prognosis indicator of HCC. Hypermethylation in the APOA1 promoter region was found in clinical samples which is in accordance with the reduction of APOA1 in HCC. The cell cycle, DNA replication, mismatch repair pathways, and tumor cell proliferation were less observed in the HCC APOA1high subgroup. The favorable immunoregulatory abilities of APOA1 showed interesting findings: a positive correlation between APOA1 and anti-tumor immune cells (NK, CD8+ T cells) and a negative association with immune cells exerting immunosuppressive effects, including M2 macrophages.

Conclusion: This is an integrative multidimensional exploration of APOA1 using bioinformatics and experiments. Both the prognostic value and anti-tumor effects based on APOA1 panoramic exploration in the HCC TME demonstrate a new potential clinical target for HCC assessment and intervention in the future.

Keywords

APOA1; HCC; NK cell; immune cells; prognosis; tumor microenvironment.

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