广西原发性肝细胞癌合并肝吸虫病患者的转录组测序分析

黄新磊, 黄在达, 彭凯, 蓝晨露, 覃海飞, 韦勇光, 廖锡文, 杨成昆, 韩创业, 朱广志

黄新磊, 黄在达, 彭凯, 蓝晨露, 覃海飞, 韦勇光, 廖锡文, 杨成昆, 韩创业, 朱广志. 广西原发性肝细胞癌合并肝吸虫病患者的转录组测序分析[J]. 广西医科大学学报, 2024, 41(5): 646-652. DOI: 10.16190/j.cnki.45-1211/r.2024.05.002
引用本文: 黄新磊, 黄在达, 彭凯, 蓝晨露, 覃海飞, 韦勇光, 廖锡文, 杨成昆, 韩创业, 朱广志. 广西原发性肝细胞癌合并肝吸虫病患者的转录组测序分析[J]. 广西医科大学学报, 2024, 41(5): 646-652. DOI: 10.16190/j.cnki.45-1211/r.2024.05.002
HUANG Xinlei, HUANG Zaida, PENG Kai, LAN Chenlu, QIN Haifei, WEI Yongguang, LIAO Xiwen, YANG Chengkun, HAN Chuangye, ZHU Guangzhi. Transcriptome sequencing analysis of primary hepatocellular carcinoma patients with hepatic trematodiasis in Guangxi[J]. Journal of Guangxi Medical University, 2024, 41(5): 646-652. DOI: 10.16190/j.cnki.45-1211/r.2024.05.002
Citation: HUANG Xinlei, HUANG Zaida, PENG Kai, LAN Chenlu, QIN Haifei, WEI Yongguang, LIAO Xiwen, YANG Chengkun, HAN Chuangye, ZHU Guangzhi. Transcriptome sequencing analysis of primary hepatocellular carcinoma patients with hepatic trematodiasis in Guangxi[J]. Journal of Guangxi Medical University, 2024, 41(5): 646-652. DOI: 10.16190/j.cnki.45-1211/r.2024.05.002

广西原发性肝细胞癌合并肝吸虫病患者的转录组测序分析

基金项目: 

国家自然科学基金资助项目(No.82360465)

详细信息
    通讯作者:

    朱广志,E-mail:zhuguangzhi0792@hotmail.com

  • 中图分类号: R735.7

Transcriptome sequencing analysis of primary hepatocellular carcinoma patients with hepatic trematodiasis in Guangxi

  • 摘要   目的:利用转录组学数据探索肝细胞癌(HCC)合并肝吸虫病的分子机制与免疫环境特征。方法:收集2022年1月至2023年12月在广西医科大学第一附属医院接受手术切除的6例HCC患者(其中3例合并肝吸虫病,3例未合并肝吸虫病)的癌组织及其癌旁组织样本,进行转录组测序。比较合并与未合并肝吸虫病的HCC患者的基因表达谱,使用“Limma”包鉴定差异表达基因,并对这些基因进行功能富集(GO)分析以确定所涉及的生物学通路。使用Cibersort算法对HCC患者肿瘤微环境中的免疫细胞浸润模式进行精确量化,并构建蛋白—蛋白相互作用(PPI)网络,揭示这些差异表达基因之间的潜在相互作用和信号传导机制。结果:从合并肝吸虫病患者中鉴定出131个差异表达基因以及31个枢纽基因,它们均与代谢和炎症信号通路相关。免疫分析显示,HCC合并肝吸虫病患者肿瘤组织中静息的记忆CD4+ T细胞浸润上调。结论:代谢途径的重编程、炎症信号通路的异常激活以及免疫微环境的改变可能共同构成了肝吸虫感染背景下HCC患者预后较差的潜在生物学基础。
    Abstract   Objective: To explore the molecular mechanism and immune environmental characteristics of hepatocellular carcinoma (HCC) with hepatic trematodiasis using transcriptomic data. Methods: The cancerous tissue and adjacent tissue samples from 6 HCC patients (3 patients with hepatic trematodiasis and 3 patients without hepatic trematodiasis) who underwent surgical resection in the First Affiliated Hospital of Guangxi Medical University from January 2022 to December 2023 were collected for transcriptome sequencing. The gene expression profiles of HCC patients with and without hepatic trematodiasis were compared, "Limma" package was used to identify differentially expressed genes (DEGs), and functional enrichment (GO) analysis of these genes was performed to determine the biological pathways involved. Cibersort algorithm was used to precisely quantify immune cell infiltration patterns in the tumor microenvironment of HCC patients and construct protein-protein interaction (PPI) networks to reveal the potential interactions and signaling mechanisms between these DEGs. Results: A total of 131 DEGs and 31 Hub gens were identified in HCC patients with hepatic trematodiasis, all of which were related to metabolic and inflammatory signaling pathways. Immunological analysis revealed an upregulation of T cells CD4+ memory resting infiltration in the tumor tissues of HCC patients with hepatic trematodiasis. Conclusion: Reprogramming of metabolic pathways, aberrant activation of inflammatory signaling pathways, and alterations in the immune microenvironment may collectively constitute contribute the potential biological basis for the poor prognosis of HCC patients with hepatic trematodiasis.
  • [1]

    NAGARAJU G P, DARIYA B, KASA P, et al. Epigenetics in hepatocellular carcinoma[J]. Seminars in cancer biology, 2022, 86(Pt 3): 622-632.

    [2]

    GOMEZ-QUIROZ L E, ROMAN S. Influence of genetic and environmental risk factors in the development of hepatocellular carcinoma in Mexico[J]. Annals of hepatology, 2022, 27(Suppl 1): 100649.

    [3]

    VILLANUEVA A. Hepatocellular carcinoma[J]. The New England journal of medicine, 2019, 380(15): 1450-1462.

    [4]

    CRAIG A J, VON FELDEN J,GARCIA-LEZANA T,et al. Tumour evolution in hepatocellular carcinoma[J]. Nature reviews gastroenterology & hepatology, 2020, 17(3): 139-152.

    [5]

    JIANG Z H, WAN X L, LV G L, et al. High prevalence of clonorchis sinensis infection in Guangxi, southern China [J]. Tropical medicine and health, 2021, 49(1): 6.

    [6]

    BOUVARD V, BAAN R, STRAIF K, et al. A review of human carcinogens--Part B: biological agents[J]. The lancet oncology, 2009, 10(4): 321-322.

    [7]

    SHI Y, JIANG Z, YANG Y, et al. Clonorchis sinensis infection and co-infection with the hepatitis B virus are important factors associated with cholangiocarcinoma and hepatocellular carcinoma[J]. Parasitology research, 2017, 116(10): 2645-2649.

    [8]

    XIA J, JIANG S C, PENG H J. Association between liver fluke infection and hepatobiliary pathological changes: a systematic review and meta-analysis[J]. Plos one, 2015, 10(7): e0132673.

    [9]

    LIN Q, TANG Z, QIN Y, et al. Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis[J]. Plos neglected tropical diseases, 2024, 18(1): e0011906.

    [10]

    LIU J Q, WANG J, HUANG X L, et al. A radiomics model based on magnetic resonance imaging to predict cytokeratin 7/19 expression and liver fluke infection of hepatocellular carcinoma[J]. Scientific reports, 2023, 13(1): 17553.

    [11]

    FAGERBERG L, HALLSTRöM B M, OKSVOLD P,et al. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibodybased proteomics[J]. Molecular & cellular proteomics: MCP, 2014, 13(2): 397-406.

    [12]

    RITCHIE M E, PHIPSON B, WU D, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies[J]. Nucleic acids research,2015, 43(7): e47.

    [13]

    YU G, WANG L G, HAN Y, et al. clusterProfiler: an R package for comparing biological themes among gene clusters[J]. Omics: a journal of integrative biology, 2012, 16(5): 284-287.

    [14]

    NEWMAN A M, LIU C L, GREEN M R, et al. Robust enumeration of cell subsets from tissue expression profiles [J]. Nature methods, 2015, 12(5): 453-457.

    [15]

    SZKLARCZYK D, FRANCESCHINI A, WYDER S,et al. STRING v10: protein-protein interaction networks, integrated over the tree of life[J]. Nucleic acids research, 2015, 43: 447-452.

    [16]

    DONCHEVA N T, MORRIS J H, GORODKIN J, et al. Cytoscape StringApp: Network Analysis and Visualization of Proteomics Data[J]. Journal of proteome research, 2019, 18(2): 623-632.

    [17]

    YOUNOSSI Z M, WONG G, ANSTEE Q M, et al. The global burden of liver disease[J]. Clinical gastroenterology and hepatology, 2023, 21(8): 1978-1991.

    [18]

    SUN J, XIN H, JIANG Z, et al. High endemicity of clonorchis sinensis infection in Binyang County, southern China[J]. PLoS neglected tropical diseases, 2020, 14(8): e0008540.

    [19]

    WANG K, SHI J H, GAO J, et al. Arachidonic acid metabolism CYP450 pathway is deregulated in hepatocellular carcinoma and associated with microvascular invasion[J]. Cell biology international, 2024, 48(1): 31-45.

    [20]

    CHEN J,GINGOLD J A,SU X.Immunomodulatory TGF-β signaling in hepatocellular carcinoma[J]. Trends in molecular medicine, 2019, 25(11): 1010-1023.

    [21]

    QI Y, HU J, LIANG J, et al. Clonorchis sinensis infection contributes to hepatocellular carcinoma progression in rat [J]. Parasitology research, 2022, 121(12): 3403-3415.

    [22]

    LAL G, SHAILA M S, NAYAK R. Booster immunization of antigen primed mice with anti-idiotypic T cells generates antigen-specific memory T cell response[J]. Vaccine, 2006, 24(8): 1149-1158.

    [23]

    REINA-CAMPOS M, SCHARPING N E, GOLDRATH A W. CD8(+) T cell metabolism in infection and cancer[J]. Nature reviews immunology, 2021, 21(11): 718-738.

  • 期刊类型引用(1)

    1. 杨文龙,张国荣. 吡喹酮对肝吸虫病患者γ-谷氨酰转肽酶、嗜酸性粒细胞水平及预后的影响. 中国地方病防治. 2025(01): 62-63 . 百度学术

    其他类型引用(0)

计量
  • 文章访问数:  54
  • HTML全文浏览量:  3
  • PDF下载量:  8
  • 被引次数: 1
出版历程
  • 收稿日期:  2024-04-15
  • 网络出版日期:  2024-07-31

目录

    /

    返回文章
    返回
    x 关闭 永久关闭