CLEC5A在胃癌组织中表达的临床意义及与肿瘤浸润免疫细胞相关性研究
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1.南京医科大学附属克州人民医院普通外科;2.南通大学附属医院生物样本库;3.南京医科大学附属克州人民医院转化医学中心

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]本研究得到了新疆自然科学基金青年基金(编号:2021D01B12)和江苏省科技厅(编号:BE2018673)的资助。


CLEC5A is a Prognostic Biomarker and Correlated With Immune Infiltrates in Gastric Cancer
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1.Department of General Surgery,Centre for Translational Medicine,Nanjing Medical University Affiliated Kizilsu People’s Hospital,Kizilsu Kirgiz;2.Centre for Translational Medicine, Nanjing Medical University Affiliated Kizilsu People’s Hospital

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This research was supported by the Youth Fund of Natural Science Foundation of Xinjiang (No.2021D01B12) and the Science and Technology Bureau of Jiangsu Province (BE2018673).

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    摘要:

    目的 观察胃癌组织中C型凝集素5A(CLEC5A)的表达状况,分析其临床意义及涉及的肿瘤浸润免疫细胞(TILs)。方法 应用生物信息学方法对癌症基因组图谱(TCGA)数据库中胃癌的高通量测序数据进行分析,探讨CLEC5A mRNA在胃癌组织表达和预后的关系;胃癌组织芯片145例胃癌[男 101例,女 44例,年龄(60.6±11.2)岁]和36例对照无癌胃黏膜组织经免疫组化染色方法分析CLEC5A蛋白表达与患者临床特征和预后的关系;应用TIMER 2.0和CIBERSORT数据库对CLEC5A mRNA的表达与肿瘤纯度及免疫浸润水平的相关性进行评估;采用多重免疫组织化学(mIHC)方法,检测免疫细胞在微环境中的分布,对生信分析得到的结果进行验证;用STRING数据库和Cytoscape工具构建CLEC5A的蛋白-蛋白相互作用(PPI)网络。结果CLEC5A mRNA在胃癌组织中的表达高于良性胃组织中的表达。免疫组化结果显示免疫荧光结果表明 CLEC5A 在肿瘤细胞和间质淋巴细胞中都有表达,胃癌组织中CLEC5A的表达(114/145,78.6%)高于正常胃黏膜组织(13/36,36.1%,p<0.05),而且其高表达提示患者预后较差。多因素分析结果表明CLEC5A高表达和TNM 分期早是胃癌患者预后相关的风险因素(均P<0.05)。TILs中CLEC5A的高表达与下淋巴结和CEA分期相关(p<0.01)。TIMER2.0和CIBERSORT分析发现CLEC5A表达增加与TILs之间呈正相关。mIHC表明,CLEC5A的表达与TILs相关,并且CLEC5A高表达组中 CD4+ T、 CD8+ T 、CD45RO+、 FOXP3+ T、 PD1+和PDL1+细胞的浸润水平高于低表达组(p<0.05)。结论 在胃癌发展中,GARP 与胃癌患者的恶性进展和预后相关并且可以很好地预测胃癌患者的总生体生存率。上调的CLEC5A表达与GC中TIL比例的增加相关,提示CLEC5A可能对胃癌患者的靶向治疗具有重要意义。

    Abstract:

    Objective: The C-type lectin 5A (CLEC5A) is a key protein involved in the inflammatory response. However, the role of CLEC5A in the prognosis and tumor-infiltrating immune cells (TILs) of Gastric cancer (GC) remains unclear. Methods:In the current study, the raw data on CLEC5A expression in GC were obtained from TCGA data bases. TIMER2.0, CIBERSORT and Tissue microarray (TMA) analysis (145 GC tissues, 36 normal gastric mucosal tissues) method were used to investigate the association between CLEC5A and TILs invasion. The roles of CLEC5A expression and clinicopathologic characteristics in prognosis of GC patients were analyzed by univariate and multivariate Cox regression analysis. Results:CLEC5A protein expression was higher in GC tissues (114/145, 78.6%) than in normal gastric mucosal tissues (13/36, 36.1%, p < 0.05), demonstrated by IHC scores in TMA. Multivariate Cox regression analysis revealed that the up-regulated CLEC5A expression in tumor cells was associated with better overall survival (OS) of GC cases. Moreover, high CLEC5A expression in TILs was correlated with lower N stage and lower CEA level (p < 0.01). Specifically, a positive correlation was identified between increased CLEC5A expression and the more TILs using TIMER2.0 and CIBERSORT analysis. The Multiplex immunohistochemical (mIHC) demonstrated that that the expression of CLEC5A is associated with TILs, and CD4+T The infiltration levels of CD8+T, CD45RO+, FOXP3+T, PD1+, and PDL1+cells were higher in the low expression group (p < 0.05). Conclusion:Together, these results indicated that up-regulated CLEC5A expression correlated with the increased proportion of immune cells and favorable prognosis in GC.

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  • 收稿日期:2025-03-27
  • 最后修改日期:2025-06-19
  • 录用日期:2026-03-24
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