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ANKRD6高表达是结肠癌不良预后的有效预测指标
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作者 赵海远 刘刚 +2 位作者 李阳 杨年钊 赵军 《南方医科大学学报》 CAS CSCD 北大核心 2023年第10期1715-1724,共10页
目的探讨ANKRD6基因在结肠癌(COAD)中的表达情况以及其在结肠癌预后和治疗中的潜在作用。方法通过免疫组化检测20例配对的结直肠腺癌组织和癌旁组织,利用实时定量PCR方法比较结肠癌细胞系和正常结肠细胞中ANKRD6基因的表达差异。通过TCG... 目的探讨ANKRD6基因在结肠癌(COAD)中的表达情况以及其在结肠癌预后和治疗中的潜在作用。方法通过免疫组化检测20例配对的结直肠腺癌组织和癌旁组织,利用实时定量PCR方法比较结肠癌细胞系和正常结肠细胞中ANKRD6基因的表达差异。通过TCGA数据库下载521例COAD患者和41例正常组织的基因表达矩阵、免疫浸润数据和临床信息,利用R软件分析ANKRD6在COAD组织中与临床病理特征的表达差异、相关基因集富集和免疫浸润情况。采用单因素和多因素Cox回归以及Kaplan-Meier方法评估COAD的预后及相关因素,并构建含ANKRD6的预后列线图。最后进行体外实验,通过Westernblot、CCK-8实验、划痕实验和Transwell检测siANKRD6与siCtrl的COAD细胞生物学活性。结果ANKRD6在COAD细胞系中高表达,并在恶性程度较高的COAD组织中表达上调(P<0.05)。ANKRD6的表达上调与COAD患者的不良预后(总体生存期和无病生存期)相关(P<0.05)。单因素和多因素Cox回归分析显示,高表达的ANKRD6与患者整体生存率相关(P<0.05)。在此基础上,构建了预后Nomogram,其C-index值为0.739,能有效地预测患者1年、3年和5年的生存预后因素,Calibration校准曲线、DCA曲线和ROC曲线评估该模型的准确性较高。免疫浸润分析结果显示,ANKRD6的表达与巨噬细胞等免疫浸润程度呈正相关(P<0.05),而与Th17细胞等免疫浸润程度呈负相关(P<0.05)。GOKEGG的富集分析结果显示,ANKRD6在COAD中主要富集于Wnt信号通路、血管内皮生长因子受体信号通路和钙信号通路等。体外实验显示,相对于siCtrl,siANKRD6可减弱COAD细胞的增殖、迁移和侵袭能力(P<0.05)。结论ANKRD6是COAD预后不良的有效预测指标,为COAD的诊断、治疗靶点的寻找和个体化治疗等提供了参考。 展开更多
关键词 结肠癌 ankrd6 肿瘤免疫浸润 预后
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Pan-cancer analyses demonstrate that ANKRD6 is associated with a poor prognosis and correlates with M2 macrophage infiltration in colon cancer 被引量:1
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作者 Rui Bai Dehao Wu +6 位作者 Zhong Shi Wangxiong Hu Juan Li Yuanyuan Chen Weiting Ge Ying Yuan Shu Zheng 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2021年第1期93-102,共10页
Objective:Ankyrin repeat domain-containing protein 6(ANKRD6)is an ankyrin repeat-containing protein which is structurally related to vertebrate inversin and Drosophila Diego.However,the correlations between ANKRD6 and... Objective:Ankyrin repeat domain-containing protein 6(ANKRD6)is an ankyrin repeat-containing protein which is structurally related to vertebrate inversin and Drosophila Diego.However,the correlations between ANKRD6 and tumor-infiltrating immune cells in cancers is not clear.Methods:ANKRD6 expression was analyzed by Oncomine,Tumor Immune Estimation Resource(TIMER)and Gene Expression Profiling Interactive Analysis(GEPIA).PrognoScan and GEPIA were used to evaluate the influence of ANKRD6 on clinical prognosis.TIMER and CIBERSORT were used to analyze correlations between ANKRD6 expression levels and tumor immune cell infiltrates.Immunohistochemical analysis of the relationship between ANKRD6 expression and overall survival,as well as the relationship between ANKRD6 expression and M2 macrophage infiltration,was performed.Results:High level of ANKRD6 expression was associated with poor prognosis of colon cancer.ANKRD6 expression level was positively correlated with infiltrating levels of CD8+T cells,CD4+T cells,macrophages,neutrophils and dendritic cells in colon cancer by using TIMER.Using CIBERSORT,we found that in plasma cells,CD8+T cells,CD4+memory resting T cells,follicular helper T cells and activated natural killer cells were significantly lower in the ANKRD6-high group than in the ANKRD6-low group.M0 and M2 macrophages were significantly higher in the ANKRD6-high group than in the ANKRD6-low group.Immunohistochemistry confirmed that M2 macrophage infiltration in the ANKRD6-high group significantly increased.Conclusions:The high ANKRD6 expression is associated with poor prognosis of colon cancer.ANKRD6 expression is positively correlated with M2 macrophage infiltration in colon cancer. 展开更多
关键词 ankrd6 colon cancer pan-cancer prognosis tumor-infiltrating
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