|Table of Contents|

Hypoxia-related gene FHDC1 expression and significance in hepatocellular carcinoma

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 19
Page:
3705-3712
Research Field:
Publishing date:

Info

Title:
Hypoxia-related gene FHDC1 expression and significance in hepatocellular carcinoma
Author(s):
LIANG Nianhai1; 2; ZHANG Dan1; DU Lijun1; XIA Huidong1; YANG Yanhui1; YANG Wei3; BAI Ru1
1.Basic Medical School,Ningxia Medical University,Ningxia Yinchuan 750004,China;2.The Fifth People's Hospital of Ningxia Hui Autonomous Region,Ningxia Shizuishan 753000,China;3.Ningxia Hospital of Integrated of Traditional Medicine and Western Medicine,Ningxia Yinchuan 750021,China.
Keywords:
FHDC1; hepatocellular carcinoma; TCGA database; prognosis; immune microenvironment
PACS:
R735.7
DOI:
10.3969/j.issn.1672-4992.2024.19.014
Abstract:
Objective:To analyze the expression and significance of hypoxia-related gene FHDC1 (FH2 domain containing 1) in hepatocellular carcinoma (HCC) and its correlation with the immune microenvironment.Methods:The expression of FHDC1 and hypoxia-inducible factor 1α (HIF-1α) in HCC and the correlation between FHDC1 and major clinicopathological features were analyzed based on the Cancer Genome Atlas (TCGA).ROC curve was used to evaluate the specificity of FHDC1 in the diagnosis of HCC.The predictive value of FHDC1 in HCC patients was analyzed by Kaplan-Meier method and Cox regression.Real-time quantitative PCR (RT-qPCR) and western blot were used to detect the mRNA and protein expression of FHDC1 and HIF-1α in HepG2 and Hep3B cells under hypoxia.The mRNA expression of FHDC1 in HCC tissues was detected by RT-qPCR,and the correlation between FHDC1 and clinical characteristics was analyzed.The relationship between FHDC1 and tumor immune microenvironment in HCC was analyzed by R package based on the TCGA.Results:FHDC1 and HIF-1α were highly expressed in HCC tissues in TCGA database (P＜0.05).FHDC1 was significantly highly expressed in HCC patients with Ⅲ and Ⅳ clinical stages,T2 and T3 stages,G3 and G4 histological grade,AFP＞ 400 ng·mL-1,vascular invasion and overall survival events of patients with death (P＜0.05).The area AUC under the ROC curve was 0.811.High expression of FHDC1 reduced the overall survival rate of patients with HCC (P＜0.01),and FHDC1 was an independent risk factor for survival (HR=0.638,P＜0.05).The mRNA and protein expression of FHDC1 and HIF-1α were significantly increased in HepG2 and Hep3B cells under hypoxia (P＜0.01).FHDC1 was highly expressed in 30 cases of clinical HCC tissues and correlated with AFP,Ⅰ and Ⅳ clinical stages (P＜0.05).The immune score and stromal score were significantly highly expressed in HCC patients with high expression of FHDC1.FHDC1 was negatively correlated with immune infiltration of dendritic cells and eosinophils (P＜0.05),and significantly positively correlated with immune infiltration of macrophages (P＜0.001).Most of the immune checkpoint genes in the high expression group of FHDC1 were also highly expressed (P＜0.05).Conclusion:Hypoxia-related gene FHDC1 is highly expressed in HCC,and is associated with poor prognosis and the immune microenvironment in HCC patients.

References:

［1］CHEN X,KOU L,XIE X,et al.Prognostic biomarkers associated with immune checkpoint inhibitors in hepatocellular carcinoma［J］.Immunology,2024,172(1):21-45.
［2］刘宗超，李哲轩，张阳，等.2020全球癌症统计报告解读［J］.肿瘤综合治疗电子杂志，2021,7(02):1-14. LIU ZC,LI ZX,ZHANG Y,et al.Interpretation of 2020 global cancer statistics report［J］.Journal of Integrated Cancer Therapy Electronic,2021,7(02):1-14.
［3］CHEN H,CHEN J,YUAN H,et al.Hypoxia-inducible factor-1α:A critical target for inhibiting the metastasis of hepatocellular carcinoma［J］.Oncology Letters,2022,24(2):284.
［4］CHEN Z,HAN F,DU Y,et al.Hypoxic microenvironment in cancer:molecular mechanisms and therapeutic interventions［J］.Signal Transduct Target Ther,2023,8(1):70.
［5］COWMAN SJ,KOH MY.Revisiting the HIF switch in the tumor and its immune microenvironment［J］.Trends Cancer,2022,8(1):28-42.
［6］林小钦，熊克宫，刘邦，等.竹节香附素A对HepG2细胞缺氧诱导因子-1α基因和蛋白表达的影响［J］.现代肿瘤医学，2017,25(15):2369-2372. LIN XQ,XIONG KG,LIU B,et al.Raddeanin A on HepG2 cells and the expression of hypoxia-inducible factor-1 alpha gene and protein in vitro［J］.Modern Oncology，2017,25(15):2369-2372.
［7］CHU Q,GU X,ZHANG Q,et al.Regulatory mechanism of HIF-1α and its role in liver diseases:a narrative review［J］.Ann Transl Med,2022,10(2):109.
［8］WANG R,ZHU H,YANG M,et al.DNA methylation profiling analysis identifies a DNA methylation signature for predicting prognosis and recurrence of lung adenocarcinoma［J］.Oncol Lett,2019,18(6):5831-5842.
［9］QU Y,LU J,MEI W,et al.Prognostic biomarkers of pancreatic cancer identified based on a competing endogenous RNA regulatory network［J］.Transl Cancer Res,2022,11(11):4019-4036.
［10］COPELAND SJ,MCRAE A,GUARGUAGLINI G,et al.Actin-dependent regulation of cilia length by the inverted formin FHDC1［J］.Mol Biol Cell,2018,29(13):1611-1627.
［11］TONG CS,SU M,SUN H,et al.Collective dynamics of actin and microtubule and its crosstalk mediated by FHDC1［J］.Front Cell Dev Biol,2024,11:1261117.
［12］KATOH M,KATOH M.Identification and characterization of human FHDC1,mouse Fhdc1 and zebrafish fhdc1 genes in silico［J］.Int J Mol Med,2004,13(6):929-934.
［13］WANG S,WANG Y,LU J,et al.LncRNA LINC00665 promotes ovarian cancer cell proliferation and inhibits apoptosis via targeting miR-181a-5p/FHDC［J］.Appl Biochem Biotechnol,2022,194(9):3819-3832.
［14］LI XL,ZHU XD,CAI H,et al.Postoperative α-fetoprotein response predicts tumor recurrence and survival after hepatectomy for hepatocellular carcinoma:A propensity score matching analysis［J］.Surgery,2019,165(6):1161-1167.
［15］BAO Q,ZENG Y,LOU Q,et al.Clinical significance of RNA methylation in hepatocellular carcinoma［J］.Cell Commun Signal,2024,22(1):204.
［16］HAO X,SUN G,ZHANG Y,et al.Targeting immune cells in the tumor microenvironment of HCC:New opportunities and challenges［J］.Front Cell Dev Biol,2021,9:775462.
［17］GUPTA T,JARPULA NS.Hepatocellular carcinoma immune microenvironment and check point inhibitors-current status［J］.World J Hepatol,2024,16(3):353-365.
［18］MINTON K.Enhancing antitumour eosinophils［J］.Nat Rev Immunol,2019,19(4):202-203.
［19］ORSI G,TOVOLI F,DADDUZIO V,et al.Prognostic role of blood eosinophil count in patients with sorafenib-treated hepatocellular carcinoma［J］.Target Oncol,2020,15(6):773-785.
［20］BIAN Z,GONG Y,HUANG T,et al.Deciphering human macrophage development at single-cell resolution［J］.Nature,2020,582(7813):571-576.
［21］程叶，蒯晴叶，张艳，等.TAM在肿瘤免疫治疗中的研究进展［J/OL］.肿瘤:1-11［2023-10-20］.http://kns.cnki.net/kcms/detail/31.1372.R.20230901.0848.002.html.DOI:10.3781/j.issn.1000-7431.2023.2209-0609. CHENG Y,KUAI QY,ZHANG Y,et al.Research progress of TAM in tumor immunotherapy［J/OL］.Tumor: 1-11［2023-10-20］.http://kns.cnki.net/kcms/detail/31.1372.R.20230901.0848.002.html.DOI:10.3781/j.issn.1000-7431.2023.2209-0609.
［22］王方园，孔宪斌，杨玉莹，等.M2型TAMs激活NF-κB通路促进结肠癌细胞侵袭转移的实验研究［J］.现代肿瘤医学，2020,28（21）：3651-3656. WANG FY,KONG XB,YANG YY,et al.The experimental study of M2 TAMs activating NF-κB pathway to promote the invasion and metastasis of colon cancer cells［J］.Modern Oncology，2020,28（21）：3651-3656.
［23］ZHANG H,DAI Z,WU W,et al.Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer［J］.J Exp Clin Cancer Res,2021,40(1):184.
［24］PESSION G,SCOTTI C,MAGGI M,et al.Hepatocellular carcinoma:Old and emerging therapeutic targets［J］.Cancers(Basel),2024,16(5):901.
［25］CUI JW,LI Y,YANG Y,et al.Tumor immunotherapy resistance:Revealing the mechanism of PD-1/PD-L1-mediated tumor immune escape［J］.Biomed Pharmacother,2024,171:116203.

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Memo:
宁夏自然科学基金（编号：2023AAC03721）
Last Update: 2024-08-30