巨噬细胞相关基因与非小细胞肺癌预后和肿瘤微环境的分析

doi:10.16288/j.yczz.23-077

遗传 ›› 2023, Vol. 45 ›› Issue (8): 684-699.doi: 10.16288/j.yczz.23-077

巨噬细胞相关基因与非小细胞肺癌预后和肿瘤微环境的分析

孙清玙(), 周阳(), 杜丽娟, 张梦珂, 王家乐, 任媛媛, 刘芳()

哈尔滨医科大学附属肿瘤医院，哈尔滨 150081

收稿日期:2023-03-28 修回日期:2023-05-21 出版日期:2023-08-20 发布日期:2023-05-29
通讯作者: 刘芳 E-mail:sun18790538507@163.com;664192792@qq.com;fangliu@hrbmu.edu.cn
作者简介:孙清玙，在读硕士研究生，专业方向：肿瘤学。E-mail: sun18790538507@163.com.|周阳，在读博士研究生，专业方向：肿瘤学。E-mail: 664192792@qq.com.
基金资助:
海燕科研基金重点项目(91339107);中青年肺癌达医科研项目横向项目(31471095);国家癌症中心攀登基金横向项目(NCC201908B11);北京科创医学发展基金会横向项目(81270113)

Analysis between macrophage-related genes with prognosis and tumor microenvironment in non-small cell lung cancer

Qingyu Sun(), Yang Zhou(), Lijuan Du, Mengke Zhang, Jiale Wang, Yuanyuan Ren, Fang Liu()

Harbin Medical University Cancer Hospital, Harbin 150081, China

Received:2023-03-28 Revised:2023-05-21 Published:2023-08-20 Online:2023-05-29
Contact: Fang Liu E-mail:sun18790538507@163.com;664192792@qq.com;fangliu@hrbmu.edu.cn
Supported by:
Major Program of Haiyan Foundation(91339107);Horizontal Project of Medical Research Project for Young and Middle-aged Lung Cancer(31471095);Horizontal Project of National Cancer Center Climbing Foundation(NCC201908B11);Horizontal Project of Beijing Science and Technology Innovation Medical Development Foundation(81270113)

摘要/Abstract

摘要：

非小细胞肺癌(non-small cell lung cancer，NSCLC)是一种高发病率和高死亡率的疾病，其预后和药物治疗效果存在个体化差异。因此,了解肺癌发生和发展的分子机制可以有效提高早期诊断和治疗，改善患者预后。巨噬细胞具有高度可塑性和异质性，是肿瘤微环境(tumor microenvironment, TME)中发挥抗肿瘤作用的关键细胞之一，在肿瘤发生发展过程中起着复杂的作用。为了阐明NSCLC中肿瘤相关巨噬细胞(tumor-associated macrophages, TAMs)相关基因在肺癌中的发生机制，本研究采用转录组测序、单因素COX回归、LASSO回归、多因素COX回归分析方法，筛选出与预后最相关的11个基因(FCRLA、LDHA、LMOD3、MAP3K8、NT5E、PDGFB、S100P、SFXN1、TDRD1、TFAP2A、TUBB6)。计算风险评分(risk score，RS)，根据RS中位数将所有样本分为高风险组和低风险组，并采用CIBERSORT反卷积算法验证RS及11个基因与巨噬细胞的相关性。上述结果表明，本研究所建立的风险评分可用于非小细胞肺癌患者预后预测，还可评估患者的免疫浸润状态，为后续肿瘤免疫治疗及基因靶向治疗提供参考。

关键词: 非小细胞肺癌, 肿瘤微环境, 肿瘤相关巨噬细胞

Abstract:

Non-small cell lung cancer (NSCLC) is a highly morbid and fatal disease that exhibits individualized differences in prognosis and drug efficacy. Therefore, understanding the molecular mechanism of the occurrence and progression of lung cancer can improve early diagnosis, treatment and prognosis. Macrophages are a crucial component of the tumor microenvironment (TME) due to their high plasticity and heterogeneity. They play a multifaceted role in tumor initiation and progression. In order to elucidate the pathogenesis of tumor-associated macrophages (TAMs) related genes in NSCLC, transcriptomic sequencing, univariate COX regression, LASSO regression and multivariate COX regression analyses were conducted to identify the 11 genes that have the most significant association with prognosis. These genes include FCRLA, LDHA, LMOD3, MAP3K8, NT5E, PDGFB, S100P, SFXN1, TDRD1, TFAP2A and TUBB6. The risk score (RS) was computed, and all samples were split into high- and low-risk groups based on the median RS. The correlation of RS and 11 genes with macrophages was verified by the CIBERSORT deconvolution algorithm. These above results suggest that the risk score developed in this study can be utilized for predicting patients' prognosis and evaluating their immune infiltration status. This study can serve as a guide for subsequent tumor immunotherapy and gene targeting therapy.

Key words: non-small cell lung cancer, tumor microenvironment, tumor-associated macrophages

孙清玙, 周阳, 杜丽娟, 张梦珂, 王家乐, 任媛媛, 刘芳. 巨噬细胞相关基因与非小细胞肺癌预后和肿瘤微环境的分析[J]. 遗传, 2023, 45(8): 684-699.

Qingyu Sun, Yang Zhou, Lijuan Du, Mengke Zhang, Jiale Wang, Yuanyuan Ren, Fang Liu. Analysis between macrophage-related genes with prognosis and tumor microenvironment in non-small cell lung cancer[J]. Hereditas(Beijing), 2023, 45(8): 684-699.

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基因	风险比(95%CI)	显著性	系数值	基因	风险比(95%CI)	显著性	系数值
FCRLA	0.90(0.83~0.97)	0.007	-0.109236	S100P	1.09(1.04~1.15)	0.001	0.0881211
LDHA	1.25(0.98~1.59)	0.073	0.2212343	SFXN1	1.26(0.93~1.71)	0.144	0.2285379
LMOD3	0.80(0.65~0.97)	0.025	-0.226136	TDRD1	0.95(0.90~1.01)	0.092	-0.050309
MAP3K8	0.76(0.62~0.93)	0.007	-0.279034	TFAP2A	1.08(1.00~1.17)	0.054	0.0776191
NT5E	1.10(1.00~1.21)	0.053	0.0965542	TUBB6	1.13(0.96~1.33)	0.142	0.1235577
PDGFB	1.31(1.10~1.56)	0.002	0.2690441

巨噬细胞相关基因与非小细胞肺癌预后和肿瘤微环境的分析

Analysis between macrophage-related genes with prognosis and tumor microenvironment in non-small cell lung cancer

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[1]	张强, 顾明亮. 单细胞测序技术及其在乳腺癌研究中的应用[J]. 遗传, 2020, 42(3): 250-268.
[2]	王诗铭, 宋晓, 赵雪莹, 陈红岩, 王久存, 吴俊杰, 高志强, 钱吉, 白春学, 李强, 韩宝惠, 卢大儒. 自噬通路基因多态性与晚期非小细胞肺癌含铂化疗疗效的相关性分析[J]. 遗传, 2017, 39(3): 250-262.
[3]	黄昀，杨焕杰，金焰，李慧敏，傅松滨. 13q14断裂重排与非小细胞肺癌转移潜能关系的研究[J]. 遗传, 2005, 27(4): 531-534.