摘要
Background:Current knowledge on apolipoprotein A1(APOA1)in hepatocellular carcinoma(HCC)is fragmented and even contradic-tory.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 cy-tometry,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 choles-terol 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 APOAihigh 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 clinicai target for HCC assessment and intervention in the future.
基金
The studies involving human participants were reviewed and approved by the Institutional Ethics Committee of the leading medical center(Shanghai Easterm Hepatobiliary Surgery Hospital,EHBHKY2020-02-012).
