胃癌中肿瘤相关中性粒细胞HIF1α的表达及预后分析OA
HIF1α expression in tumor-associated neutrophils and its prognostic significance in gastric cancer
目的 探讨HIF1α在胃癌肿瘤微环境(tumor microenvironment,TME)免疫细胞,特别是肿瘤相关中性粒细胞(tumor-associated neutrophils,TANs)中的表达,并鉴定其细胞来源及其临床预后价值.方法 收集225例胃腺癌手术标本,构建组织芯片.采用免疫组化EnVision法检测HIF1α及多种免疫细胞标志物(CD15、CD68、CD3、CD20、SMA、CD34)的表达.通过多色免疫荧光技术对CD15与HIF1α表达进行共定位分析,以鉴定HIF1α+TANs.分析HIF1α表达与临床病理特征的相关性,并利用Kaplan-Meier生存分析和Cox比例风险回归模型评估其预后意义.结果 胃癌间质中HIF1α高表达与晚期TNM分期显著相关(P=0.028).相关性分析显示,HIF1α表达与中性粒细胞标志物CD15呈中等程度正相关(rs=0.378,P＜0.001),而与巨噬细胞、T细胞、B细胞等标志物无相关性.多色免疫荧光检测证实CD15+HIF1α+TANs亚群的存在.生存分析显示,CD15与HIF1α共同高表达的(CD15+/HIF1α+)患者预后最差(P＜0.001).多因素Cox分析证实,CD15/HIF1α组合表达是影响患者总生存期的独立危险因素(HR=1.444,95%CI:1.019～2.045,P=0.039).结论 HIF1α主要表达于胃癌TME中的TANs,CD15+HIF1α+TANs可能代表一个与肿瘤恶性进展和不良预后密切相关的细胞亚群."CD15/HIF1α组合表达"可作为潜在的预后生物学标志物,并为靶向胃癌缺氧微环境及TANs的联合治疗策略提供了新的理论依据.
Objective To investigate HIF1α expression,its cellular source,and its prognostic significance in immune cells,particularly tumor-associated neutrophils(TANs),within the tumor microenvironment(TME)of gas-tric cancer.Methods Tissue microarrays were constructed from 225 gastric adenocarcinoma resection specimens.Im-munohistochemistry EnVision method was used to assess HIF1α and immune/stromal cell markers(CD15,CD68,CD3,CD20,SMA,and CD34).Multiplex immunofluorescence was performed to colocalize CD15 and HIF1α and identify HIF1α+TANs.Associations between HIF1α expression and clinicopathological features were analyzed,and prognostic significance was evaluated using Kaplan-Meier analysis and Cox proportional hazards regression.Results High stromal HIF1α expression was significantly associated with advanced TNM stage(P=0.028).HIF1α expression showed a moderate positive correlation with the neutrophil marker CD15(rs=0.378,P＜0.001)but no significant cor-relation with macrophage,T-cell,or B-cell markers.Multiplex immunofluorescence confirmed a CD15+/HIF1α+TAN subpopulation.Patients with concomitantly high CD15 and HIF1α expression(CD15+/HIF1α+)had the poorest prog-nosis(P＜0.001).Multivariate Cox analysis identified combined CD15/HIF1α expression as an independent risk fac-tor for overall survival(HR=1.444,95%CI:1.019-2.045,P=0.039).Conclusion HIF1α is predominantly ex-pressed in TANs within the gastric cancer TME,and CD15+/HIF1α+TANs may represent a subpopulation closely asso-ciated with tumor progression and poor prognosis.Combined CD15/HIF1α expression may serve as a prognostic bio-marker and provide a rationale for combination strategies targeting the hypoxic TME and TANs in gastric cancer.
季月霞;梁栋;陈敏;宛传丹;徐逸;张晗婕;陶静霞;郭天威
南京中医药大学常熟附属医院病理科,常熟 215500南京中医药大学常熟附属医院胃肠外科,常熟 215500南京中医药大学常熟附属医院胃肠外科,常熟 215500常熟市医学检验所,常熟 215500南京中医药大学常熟附属医院病理科,常熟 215500南京中医药大学常熟附属医院病理科,常熟 215500南京中医药大学常熟附属医院病理科,常熟 215500南京中医药大学常熟附属医院病理科,常熟 215500
医药卫生
胃肿瘤肿瘤微环境HIF1α肿瘤相关中性粒细胞预后
gastric neoplasmstumor microenvironmentHIF1αtumor-associated neutrophilsprognosis
《临床与实验病理学杂志》 2026 (8)
1040-1047,8
南京中医药大学校自然重点项目(XZR2024048)、苏州市科技局科技发展项目(SKY2023084)、常熟市卫健委科技发展重点项目(csws202023) Key Project of Natural Science Research of Nanjing University of Chinese Medicine(XZR2024048)Science and Technology Development Project of Suzhou Science and Technology Bureau(SKY2023084)Key Science and Technology Development Project of Changshu Health Commission(csws202023)
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