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中华肝脏外科手术学电子杂志 ›› 2025, Vol. 14 ›› Issue (05) : 716 -724. doi: 10.3877/cma.j.issn.2095-3232.2025.05.009

临床研究

基于多组学分析MCAM在肝癌中表达及其与生存预后和免疫细胞浸润的关系
方兴保1, 庞国莲2, 李月宏1, 蔡艳3,()   
  1. 1 655000 云南省 曲靖市,昆明医科大学附属曲靖医院(曲靖市第一人民医院)肝胆胰外科
    2 655000 云南省 曲靖市,昆明医科大学附属曲靖医院(曲靖市第一人民医院)病理科
    3 655000 云南省 曲靖市,曲靖健康医学院病理教研室
  • 收稿日期:2025-05-10 出版日期:2025-10-10
  • 通信作者: 蔡艳
  • 基金资助:
    云南省基础研究计划昆医联合专项重点项目(202301AY070001-019); 云南省基础研究计划昆医联合专项面上项目(202401AY070001-260); 云南省教育厅科学研究基金项目(2025J1662)

Multiomics-based analysis of expression of MCAM in hepatocellular carcinoma and its relationship with survival prognosis and immune cell infiltration

Xingbao Fang1, Guolian Pang2, Yuehong Li1, Yan Cai,3()   

  1. 1 Department of Hepatobiliary and Pancreatic Surgery, Qujing Hospital affiliated to Kunming Medical University (Qujing No.1 Hospital), Qujing 655000, China
    2 Department of Pathology, Qujing Hospital Affiliated to Kunming Medical University (Qujing the First People's Hospital), Qujing 655000, China
    3 Pathology Teaching and Research Section, Qujing Health Medical College, Qujing 655000, China
  • Received:2025-05-10 Published:2025-10-10
  • Corresponding author: Yan Cai
引用本文:

方兴保, 庞国莲, 李月宏, 蔡艳. 基于多组学分析MCAM在肝癌中表达及其与生存预后和免疫细胞浸润的关系[J/OL]. 中华肝脏外科手术学电子杂志, 2025, 14(05): 716-724.

Xingbao Fang, Guolian Pang, Yuehong Li, Yan Cai. Multiomics-based analysis of expression of MCAM in hepatocellular carcinoma and its relationship with survival prognosis and immune cell infiltration[J/OL]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2025, 14(05): 716-724.

目的

探讨黑色素瘤细胞黏附分子(MCAM)在肝细胞癌(肝癌)中表达、生物功能、临床相关性及其在患者生存预后、免疫治疗反应中作用。

方法

从TCGA、UCSC,Xena和GEO数据库中检索MCAM mRNA表达数据和临床信息。使用ggplot2进行差异表达分析。使用“survival”和“survminer”R包进行生存分析。MCAM蛋白表达通过临床蛋白质组学肿瘤分析联盟(CPTAC)数据库进行评估。通过LinkedOmics进行基因本体(GO)功能和KEGG通路富集分析。使用单样本基因集富集分析(ssGSEA)和TIMER数据库评估免疫细胞浸润和免疫检查点关系。通过临床标本进行免疫组化验证。利用BEST数据库预测免疫治疗反应。

结果

基于TCGA-LIHC数据集、GEO数据库、UALCA、CPTACP数据库的多组学分析显示,肝癌组织MCAM高表达。TCGA-LIHC数据集中MCAM高表达患者总体生存期(OS)及无进展生存期(PFS)明显低于低表达患者(HR=0.70,0.68;P<0.05)。GSE144269及GSE54236中高表达MCAM患者OS明显低于低表达患者(HR=0.67,0.72;P<0.05)。UALCA数据库分析显示,高表达MCAM患者与肝癌临床分期、肿瘤分级和淋巴结转移呈正相关(P<0.05)。MCAM表达在TCGA-LIHC数据集ROC曲线下面积(AUC)为0.921,95%CI:0.887~0.954,MCAM具有良好的诊断效能。GO功能和KEGG通路富集分析显示,MCAM共表达基因参与免疫反应通路,包括Th1/Th2细胞分化。MCAM高表达明显影响免疫细胞浸润水平及参与多种促癌信号通路。免疫组化证实肝癌组织中MCAM蛋白水平高表达。BEST分析表明,MCAM高表达可能预测对PD-1、PD-L1和CTLA-4靶向治疗的更好反应。

结论

肝癌中MCAM高表达,其高表达与患者不良预后和免疫调节相关,MCAM可作为癌症预后的有价值生物标志物和免疫治疗疗效的潜在预测因子。

Objective

To investigate the expression, biological function and clinical relevance of melanoma cell adhesion molecule (MCAM) in hepatocellular carcinoma (HCC), and its role in the survival prognosis and immunotherapy response of HCC patients.

Methods

The MCAM mRNA expression level and clinical information were retrieved from TCGA, UCSC Xena and GEO databases. Differential expression analysis was performed using ggplot2. The "survival" and "survminer" R packages were used for survival analysis. The expression of MCAM protein was evaluated by the data base of Clinical Proteomic Tumor Analysis Consortium (CPTAC). Gene ontology (GO) functional and KEGG pathway enrichment analyses were conducted by LinkedOmics. Single-sample gene set enrichment analysis (ssGSEA) and TIMER database were used to evaluate the relationship between immune cell infiltration and immune checkpoints. Immunohistochemical assay was validated by using clinical samples. The response to immunotherapy was predicted by the BEST database.

Results

Multiomics analysis based on the TCGA-LIHC data set, GEO, UALCA and CPTACP databases showed that MCAM was highly expressed in HCC tissues. In TCGA-LIHC data set, the overall survival (OS) and progression-free survival (PFS) of patients with high expression of MCAM were significantly lower than those with low MCAM expression (HR=0.70, 0.68; both P<0.05). In GSE144269 and GSE54236 databases, the OS of patients with high expression of MCAM was lower than that of patients with low MCAM expression (HR=0.67, 0.72; both P<0.05). UALCA database demonstrated that high expression of MCAM in HCC patients was positively correlated with clinical stage, tumor grade and lymph node metastasis (all P<0.05). In TCGA-LIHC data set, the area under the ROC curve (AUC) of MCAM expression was 0.921 (95%CI: 0.887-0.954), indicating that MCAM had high diagnostic efficiency. GO functional and KEGG pathway enrichment analyses showed that the co-expressed genes of MCAM participated in the immune response pathway, including Th1/Th2 cell differentiation. High MCAM expression significantly affected the level of immune cell infiltration and participated in multiple cancer-promoting signal pathways. Immunohistochemistry found high expression of MCAM protein in HCC tissues. BEST analysis demonstrated that high MCAM expression might predict better response to targeted therapy of PD-1, PD-L1 and CTLA-4.

Conclusions

MCAM is highly expressed in HCC, which is associated with poor prognosis and immune regulation of HCC patients. MCAM can be used as a valuable biomarker for cancer prognosis and a potential predictor for clinical efficacy of immunotherapy.

图1 CPTACP数据库分析MCAM在泛癌组织中的表达 注:ns为P>0.05,**为P<0.01,***为P<0.001;MCAM为黑色素瘤细胞黏附分子
图2 数据库分析MCAM在肝癌中的表达 注:a为TCGA-LIHC数据库正常肝组织与肝癌组织比较;b为TCGA-LIHC数据库癌与癌旁配对组织比较,c为GSE144269数据集;d为GSE54236数据集;e为UALCAN数据库;f为CPTAC数据库;***为P<0.001;MCAM为黑色素瘤细胞黏附分子
图3 数据库分析MCAM表达与肝癌患者预后关系 注:a为TCGA-LIHC数据库OS;b为TCGA-LIHC数据库PFS;MCAM为黑色素瘤细胞黏附分子
图4 MCAM的GO功能分析 注:MCAM为黑色素瘤细胞黏附分子
图5 MCAM与免疫细胞浸润相关性 注:MCAM为黑色素瘤细胞黏附分子
图6 肝癌中MCAM免疫组化表达(×400) 注:MCAM为黑色素瘤细胞黏附分子
图7 MCAM与免疫治疗反应预测的关系 注:MCAM为黑色素瘤细胞黏附分子
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