宫颈癌组织中机械敏感离子通道蛋白1表达变化及M1/M2型巨噬细胞浸润情况观察分析OACSTPCD
Expression changes of mechanosensitive ion channel protein 1 in cervical cancer tissues and the infiltration of M1/M2 macrophages
目的 观察宫颈癌组织中机械敏感离子通道蛋白1(Piezo-type mechanosensitive ion channel component 1,Piezo1)的表达变化及M1/M2型巨噬细胞浸润情况,探讨其可能作用机制.方法 选择病理明确诊断为宫颈癌患者的宫颈癌组织35例份、子宫肌瘤或子宫腺肌瘤行子宫全切患者正常宫颈组织30例份,分别采用免疫组织化学染色法及Western Blotting法检测Piezo1.从TCGA宫颈癌RNA-seq数据库中,使用R 软件通过CIBERSORT法分析不同Piezo1表达的宫颈癌组织22种免疫细胞浸润情况,利用GSEA 4.2.3软件筛选1NES1>1、P<0.05、FDR<0.25的Piezo1巨噬细胞相关信号通路.采用免疫组织化学染色法和Pearson相关性分析法分析Piezo1表达与宫颈癌组织M1/M2巨噬细胞浸润的相关性.结果 与正常宫颈组织相比,宫颈癌组织Piezo1相对表达量高(P<0.05).宫颈癌组织和正常宫颈组织中M1巨噬细胞浸润强度为7.70±1.31、7.17±2.05(P>0.05),M2巨噬细胞浸润强度分别为16.21±6.36、3.89±1.56(P<0.05).Piezo1表达与宫颈癌组织M2型巨噬细胞浸润水平成正相关(r=0.861 7,P<0.001).与Piezo1低表达者相比,Piezo1高表达的宫颈癌组织M2型巨噬细胞比例高(P<0.01).Piezo1与M2型巨噬细胞极化细胞相关信号通路主要有IL6/JAK/STAT3信号通路、TGF-β信号通路及TNF-α/NF-κB信号通路.结论 Piezo1在宫颈癌组织中高表达、M2巨噬细胞浸润多.Piezo1可能通过激活宫颈癌组织IL6/JAK/STAT3信号通路、TGF-β信号通路和TNF-α/NF-κB信号通路,促进M2型巨噬细胞极化,参与宫颈癌的发生发展.
Objective To observe the expression changes of mechanosensitive ion channel protein 1(Piezo1)in cer-vical cancer tissues and the infiltration of M1/M2 macrophages,and to explore their possible mechanisms.Methods Thirty-five cervical cancer tissue samples from patients with the pathological diagnosis of cervical cancer and 30 normal cervical tissue samples from patients undergoing total hysterectomy for uterine fibroids or adenomyosis were selected.Im-munohistochemistry and Western blotting were used to detect Piezo1.The CIBERSORT method was used to analyze the infiltration of 22 types of immune cells in cervical cancer tissues with different Piezo1 expression from the TCGA cervical cancer RNA-seq database using R software.GSEA 4.2.3 software was used to screen for Piezo1-related macrophage sig-naling pathways with|NES|>1,P<0.05,and FDR<0.25.The correlation between Piezo1 expression and M1/M2 macrophage infiltration in cervical cancer tissues was analyzed using immunohistochemistry and Pearson correlation analy-sis.Results Compared with the normal cervical tissues,the relative expression level of Piezo1 in the cervical cancer tissues was higher(P<0.05).The infiltration intensities of M1 macrophages in cervical cancer tissues and normal cervical tissues were 7.70±1.31 and 7.17±2.05,respectively(both P>0.05),while the infiltration intensities of M2 macro-phages were 16.21±6.36 and 3.89±1.56,respectively(both P<0.05).The expression of Piezo1 was positively corre-lated with the level of M2 macrophage infiltration in cervical cancer tissues(r=0.8617,P<0.001).Compared with those with low Piezo1 expression,cervical cancer tissues with high Piezo1 expression had a higher proportion of M2 macro-phages(P<0.01).The signaling pathways related to Piezo1 and M2 macrophage polarization mainly included the IL6/JAK/STAT3 signaling pathway,TGF-β signaling pathway,and TNF-α/NF-κB signaling pathway.Conclusion Piezo1 is highly expressed in cervical cancer tissues,and there is significant infiltration of M2 macrophages.Piezo1 may promote the polarization of M2 macrophages by activating the IL6/JAK/STAT3 signaling pathway,TGF-β signaling pathway,and TNF-α/NF-κB signaling pathway in cervical cancer tissues,thus participating in the development and progression of cer-vical cancer.
廖文欣;李洋;刘婷婷;申复进
武汉大学人民医院妇产科,武汉 430000
临床医学
机械敏感离子通道蛋白1巨噬细胞M2型巨噬细胞宫颈癌
mechanosensitive ion channel protein 1macrophagesM2 macrophagescervical carcinoma
《山东医药》 2024 (030)
10-13 / 4
湖北省自然科学基金面上项目(2021CFB430);中央高校基本科研业务费专项资金(2042022kf1110).
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