Plasma exosomal CD48 protein as a candidate diagnostic biomarker for hepatocellular carcinoma

Yicai CHENG; Zhenhua DU; Zhijuan FAN; Lan FENG; Pengbo CAO; Gangqiao ZHOU

doi:10.19401/j.cnki.1007-3639.2022.11.005

您当前的位置：

首页 >

文章列表页 >

Plasma exosomal CD48 protein as a candidate diagnostic biomarker for hepatocellular carcinoma

Article | 更新时间：2025-12-31

- Plasma exosomal CD48 protein as a candidate diagnostic biomarker for hepatocellular carcinoma
- China Oncology Vol. 32, Issue 11, Pages: 1074-1083(2022)
- 作者机构：
  
  1. 南华大学衡阳医学院，湖南衡阳 421000
  2. 军事科学院军事医学研究院辐射医学研究所，蛋白质组学国家重点实验室，国家蛋白质科学中心，北京 100850
  3. 天津市武警特色医学中心检验科，天津 300160
  4. 天津市第三中心医院医学重点学科（专科），天津 300170
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2022.11.005
  CLC： R735.7
- Received：15 February 2022，
  
  Revised：2022-04-30，
  
  Published：30 November 2022
- 稿件说明：
移动端阅览
Yicai CHENG, Zhenhua DU, Zhijuan FAN, et al. Plasma exosomal CD48 protein as a candidate diagnostic biomarker for hepatocellular carcinoma[J]. China Oncology, 2022, 32(11): 1074-1083.
DOI：

Yicai CHENG, Zhenhua DU, Zhijuan FAN, et al. Plasma exosomal CD48 protein as a candidate diagnostic biomarker for hepatocellular carcinoma[J]. China Oncology, 2022, 32(11): 1074-1083. DOI： 10.19401/j.cnki.1007-3639.2022.11.005.

摘要

背景与目的：

约60%的肝细胞癌（hepatocellular carcinoma，HCC）患者在晚期才被确诊，因而无法得到及时有效的治疗，目前临床上常用于HCC诊断的血清标志物的灵敏度均偏低。本研究通过分析血浆外泌体蛋白质组的表达差异，鉴定可能用于HCC诊断的候选外泌体蛋白质标志物。

方法：

首先，采用鸟枪法蛋白质组质谱分析方法，对发掘人群[包括4名健康对照者（healthy control，HC）组和4例HCC患者组

]

的血浆外泌体进行全蛋白质组的定性和定量分析，并筛选差异表达蛋白质。然后，采用酶联免疫吸附试验（enzyme-linked immunosorbent assay，ELISA）在独立的验证人群[包括56例HCC患者组、20例肝硬化（liver cirrhosis，LC）患者组和48名HC组

]

中进行验证实验，并评估候选蛋白质分子在HCC诊断中的潜在价值。

结果：

在发掘人群中，共鉴定到1 434种血浆外泌体蛋白质，其中的CD48蛋白在HCC患者中的表达水平显著高于HC组个体。进一步采用ELISA在独立验证人群中证实CD48蛋白在HCC患者中的表达水平显著高于LC和HC个体，受试者工作特征（receiver operating characteristic，ROC）曲线的曲线下面积（area under curve，AUC）为0.886。当联合检测血浆外泌体中的CD48蛋白和血浆中的甲胎蛋白（alpha-fetoprotein，AFP）时，AUC可提升至0.970。

结论：

血浆外泌体中的CD48蛋白可能作为HCC的候选诊断标志物，当其与AFP联合应用时可能进一步提高HCC的临床诊断能力。

Abstract

Background and purpose:

Approximately 60% of patients with hepatocellular carcinoma (HCC) are diagno

sed at an advanced stage

therefore cannot receive timely and effective treatment. At present

the sensitivity of serum biomarkers commonly used in the diagnosis of HCC is low. In this paper

through the differential expression analysis of plasma exosomal proteome

the candidate exosome protein markers which may be used in the diagnosis of HCC were identified.

Methods:

First

we performed shot-gun proteome mass spectrometry assays in the plasma exosomes from the discovery cohort [including 4 healthy control (HC) group and 4 HCC patients group

]

and identified differentially expressed proteins by qualitative and quantitative analyses. Then

we carried out enzyme-linked immunosorbent assay (ELISA) in plasma samples of an independent verification cohort [including 56 HCC patients group

20 liver cirrhosis (LC) patients group and 48 HC group

]

and evaluated the diagnostic value of the candidate protein in HCC.

Results:

In the discovery cohort

we identified a total of 1 434 exosomal proteins

of which CD48 exhibited higher levels in HCC than in HC. We further verified in the validation cohort by ELISA that CD48 was markedly higher in HCC compared with LC and HC groups

with the area under receiver operating characteristic (ROC) curve (AUC) of 0.886. When combined with plasma alpha-fetoprotein (AFP)

the AUC reached 0.970.

Conclusion:

The plasma exosomal CD48 protein can be used as a candidate diagnostic biomarker for HCC

and its combination with AFP may further improve the clinical diagnostic ability for HCC.

关键词

Keywords

references

SUNG H , FERLAY J , SIEGEL R L , et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J ] . CA Cancer J Clin , 2021 , 71 ( 3 ): 209 - 249 . DOI: 10.3322/caac.21660 http://doi.org/10.3322/caac.21660 https://onlinelibrary.wiley.com/doi/10.3322/caac.21660 https://onlinelibrary.wiley.com/doi/10.3322/caac.21660

WANG M J , WANG Y T , FENG X S , et al. Contribution of hepatitis B virus and hepatitis C virus to liver cancer in China north areas: experience of the Chinese National Cancer Center [J ] . Int J Infect Dis , 2017 , 65 : 15 - 21 . DOI: S1201-9712(17)30227-8 http://doi.org/S1201-9712(17)30227-8

中国临床肿瘤学会(CSCO) . 原发性肝癌诊疗指南(2020) [M ] . 人民卫生出版社 , 2020 .

Chinese society of clinical oncology (CSCO) . Guidelines for diagnosis and treatment of primary liver cancer (2020) [M ] .People’s Health Publishing House[J ] , 2020. 2020 .

TAYOB N , LOK A S , DO K A , et al. Improved detection of hepatocellular carcinoma by using a longitudinal alpha-fetoprotein screening algorithm [J ] . Clin Gastroenterol Hepatol , 2016 , 14 ( 3 ): 469 - 475 .e2. DOI: 10.1016/j.cgh.2015.07.049 http://doi.org/10.1016/j.cgh.2015.07.049 https://linkinghub.elsevier.com/retrieve/pii/S1542356515010691 https://linkinghub.elsevier.com/retrieve/pii/S1542356515010691

PAN B T , TENG K , WU C , et al. Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes [J ] . J Cell Biol , 1985 , 101 ( 3 ): 942 - 948 .

YU W , HURLEY J , ROBERTS D , et al. Exosome-based liquid biopsies in cancer: opportunities and challenges [J ] . Ann Oncol , 2021 , 32 ( 4 ): 466 - 477 . DOI: 10.1016/j.annonc.2021.01.074 http://doi.org/10.1016/j.annonc.2021.01.074

GE Y , MU W , BA Q , et al. Hepatocellular carcinoma-derived exosomes in organotropic metastasis, recurrence and early diagnosis application [J ] . Cancer Lett , 2020 , 477 : 41 - 48 . DOI: S0304-3835(20)30065-3 http://doi.org/S0304-3835(20)30065-3

BRUIX J , SHERMAN M , American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update [J ] . Hepatology , 2011 , 53 ( 3 ): 1020 - 1022 . DOI: 10.1002/hep.24199 http://doi.org/10.1002/hep.24199

KINOSHITA A , ONODA H , FUSHIYA N , et al. Staging systems for hepatocellular carcinoma: current status and future perspectives [J ] . World J Hepatol , 2015 , 7 ( 3 ): 406 - 424 . DOI: 10.4254/wjh.v7.i3.406 http://doi.org/10.4254/wjh.v7.i3.406

WILD C P , HALL A J . Primary prevention of hepatocellular carcinoma in developing countries [J ] . Mutat Res Mutat Res , 2000 , 462 ( 2/3 ): 381 - 393 .

LI M Y , ZHAO C , CHEN L , et al. Quantitative proteomic analysis of plasma exosomes to identify the candidate biomarker of imatinib resistance in chronic myeloid leukemia patients [J ] . Front Oncol , 2021 , 11 : 779567 . DOI: 10.3389/fonc.2021.779567 http://doi.org/10.3389/fonc.2021.779567 https://www.frontiersin.org/articles/10.3389/fonc.2021.779567/full https://www.frontiersin.org/articles/10.3389/fonc.2021.779567/full

WHITESIDE T L . Cytokine assays [J ] . BioTechniques , 2002 , Suppl: 4 - 8 , 10, 12 - 15 .

MONDELLO S , GUEDES V A , LAI C , et al. Circulating brain injury exosomal proteins following moderate-to-severe traumatic brain injury: temporal profile, outcome prediction and therapy implications [J ] . Cells , 2020 , 9 ( 4 ): E977 .

VAUGHAN H A , HENNING M M , PURCELL D F , et al. The isolation of cDNA clones for CD48 [J ] . Immunogenetics , 1991 , 33 ( 2 ): 113 - 117 .

TARAZONA R , DELGADO E , GUARNIZO M C , et al. Human prostasomes express CD48 and interfere with NK cell function [J ] . Immunobiology , 2011 , 216 ( 1/2 ): 41 - 46 . DOI: 10.1016/j.imbio.2010.03.002 http://doi.org/10.1016/j.imbio.2010.03.002 https://linkinghub.elsevier.com/retrieve/pii/S0171298510000252 https://linkinghub.elsevier.com/retrieve/pii/S0171298510000252

AALBERTS M , STOUT T A E , STOORVOGEL W . Prostasomes: extracellular vesicles from the prostate [J ] . Reprod Camb Engl , 2014 , 147 ( 1 ): R1 -R14.

ZHU N Q , HOU J Y . Assessing immune infiltration and the tumor microenvironment for the diagnosis and prognosis of sarcoma [J ] . Cancer Cell Int , 2020 , 20 ( 1 ): 577 . DOI: 10.1186/s12935-020-01672-3 http://doi.org/10.1186/s12935-020-01672-3

Views

2467

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Preliminary study on the role and mechanism of ISG15 in exosomes in platinum resistance in ovarian cancer

PARP1 promotes the progression of hepatocellular carcinoma by regulating expression of POU2F2

Significance of infiltration of M1 tumor-associated macrophages in hepatocellular carcinoma

Progress in research, diagnosis, and treatment of hepatocellular carcinoma in 2022

Mechanism of LINC00601 in regulating sensitivity of hepatocellular carcinoma cells to oxaliplatin chemotherapy

Related Author

Yanan TIAN

Hui ZHENG

Tianqing YAN

Heng ZHANG

Renquan LU

Lin GUO

Ziqiang WEN

Junliang LAN

Related Institution

Department of Clinical Laboratory, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University

Department of Hepatobiliary Surgery, Linfen People’s Hospital, The Seventh Clinical Medical College of Shanxi Medical University

Clinical Medicine, Major of Medical College Nantong University

Department of Surgery, the Third People’s Hospital of Nantong, Affiliated Nantong Hospital Three of Nantong University

Department of Pathology, the Third People's Hospital of Nantong, Affiliated Nantong Hospital Three of Nantong University

AI问答

⁰