摘要
背景与目的肿瘤微环境是肿瘤细胞赖以生存的复杂环境。其中肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)、肿瘤新生血管及程序性死亡受体1/程序性死亡受体-配体1(programmed cell death protein 1/programmed cell death ligand 1,PD-1/PD-L1)作为关键部分,在肿瘤发生、发展过程中起重要作用,影响患者预后。本研究旨在阐明TAMs、肿瘤新生血管和PD-L1的表达与非小细胞肺癌(non-small cell lung cancer,NSCLC)临床病理特征的相关性,并探讨它们对NSCLC预后的影响。方法收集92例NSCLC患者的临床病理资料及手术标本,采用免疫组化法检测癌组织和癌旁组织中TAMs、肿瘤新生血管和PD-L1的表达,采用配备有Olympus-DP72图像采集系统的OlympusBX51正置显微镜进行拍照并用Image-pro Plus 6.0软件进行半定量分析。结果癌组织与癌旁组织中TA Ms、肿瘤新生血管和PD-L1的表达差异无统计学意义(P>0.05)。根据肿瘤微环境中各组分的定量表达,可将其分为低、中、高表达组。癌组织中TAMs的低、中和高密度组的中位总生存(overall survival,OS)分别是36个月(95%CI:25.3-46.7)、26个月(95%CI:12.2-39.8)和16个月(95%CI:9.4-22.6),差异具有统计学意义(P=0.016);肿瘤新生血管的低、中和高密度组的中位OS分别为30个月(95%CI:22.5-37.5)、28个月(95%CI:18.1-37.9)和25个月(95%CI:14.6-35.4),差异无统计学意义(P=0.626);PD-L1的低、中和高表达组的中位OS分别为35个月(95%CI:29.4-40.6),28个月(95%CI:13.6-42.4)和17个月(95%CI:10.5-23.5),差异具有统计学意义(P=0.002)。联合低、中和高表达组的中位OS分别为36个月(95%CI:30.6-41.4)、26个月(95%CI:19.2-32.8)和9个月(95%CI:4.4-13.6),差异具有统计学意义(P=0.001)。Cox回归分析结果显示,病理分型、TAMs和PD-L1均为肺癌患者的独立预后因素。结论肿瘤微环境关键成分PD-L1及TAMs的表达与NSCLC患者的预后密切相关。
Background and Objective Tumor microenvironment is a complex and dynamic community, which plays a crucial role in tumor progression via the co-evolution of cancer cells and tumor stroma. Among them, tumorassociated macrophages(TAMs) and tumor neo-vessels are two key components in the tumor microenvironment during cancer invasion. In addition, programmed cell death ligand 1/programmed cell death ligand 1(PD-1/PD-L1) also plays an important role in tumorigenesis and development, and the clinical strategies to block PD-1/PD-L1 pathway could have great benefits for cancer patients. This study was aimed at analyzing the quantitative expression and prognostic significance of TAMs, tumor neo-vessels and PD-L1 in tumor microenvironment and exploring the relations between the expression of above components with the patients’ prognosis of non-small cell lung cancer(NSCLC). Methods Clinicopathological data and surgical specimens of 92 patients with NSCLC were collected, and immunohistochemistry was used to stain the expression of TAMs, tumor neo-vessels and PD-L1 on tumor tissue and peri-tumor tissues. The inverted microscopy was used to take pictures and Image-pro Plus 6.0 software was used for quantitative analysis. The clinicopathological characteristics and overall survival(OS) were analyzed. Results The median OS of 92 NSCLC cases was 22.5 month. The expression of TAMs, tumor neo-vessels and PD-L1 in tumor tissue and peri-tumor tissues were not statistically significant(P>0.05). According to the cutoff of above key three components in tumor microenvironment, all the cases could be classified into high, middle and low expression groups. The survival analysis demonstrated that the OS in high expression group of TAMs(P=0.016) and PD-L1(P=0.002) was shorter than the other two groups, respectively, with statistical significance. The OS in high tumor neo vessels group was shorter than the other two groups. However, there was no statistical significance between these three group(P=0.626). Combined with above the three compo
作者
杭青青
应航洁
程国平
杨世锋
金佳男
陈亚梅
陈奇勋
蒋友华
赵强
方敏
陈明
赖霄晶
Qingqing HANG;Hangjie YING;Guoping CHENG;Shifeng YANG;Jianan JIN;Yamei CHEN;Qixun CHEN;Youhua JIANG;Qiang ZHAO;Min FANG;Ming CHEN;Xiaojing LAI(The Second Clinical Medical College Zhejiang Chinese Medical University,Hangzhou 310053,China;Zhejiang Key Laboratory of Radiation Oncology,Department of Thoracic Radiotherapy,Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital),Institute of Cancer and Basic Medicine(IBMC),Chinese Academy of Sciences,Hangzhou 310022,China;Department of Pathology,Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital),Institute of Cancer and Basic Medicine(IBMC),Chinese Academy of Sciences,Hangzhou 310022,China;Department of Thoracic Surgery,Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital),Institute of Cancer and Basic Medicine(IBMC),Chinese Academy of Sciences,Hangzhou 310022,China)
出处
《中国肺癌杂志》
CAS
CSCD
北大核心
2020年第10期837-844,共8页
Chinese Journal of Lung Cancer
基金
国家自然科学基金项目(No.81703018)
浙江省医药卫生科技计划项目(No.2020KY466)资助。
