收稿日期: 2023-12-27
网络出版日期: 2024-03-08
基金资助
国家自然科学基金资助项目(82174453);北京市自然科学基金资助项目(7222270)
The causal relationship between chemokine CCL2 and lung cancer: a two⁃sample Mendelian randomization study
Received date: 2023-12-27
Online published: 2024-03-08
目的 探究趋化因子CCL2(又称单核细胞趋化蛋白1,MCP-1)与肺癌(lung cancer)是否具有因果关系。 方法 从全基因组关联研究(GWAS)提取趋化因子CCL2和肺癌不同病理分型的遗传数据,使用逆方差加权分析(IVW)作为主要分析,另选用加权中位数法、简单模式法、MR-Egger回归法、加权模式法进行补充分析,并进行敏感性分析验证数据的可靠性。 结果 趋化因子CCL2对肺腺癌的IVW分析结果OR = 1.065,95%CI(0.919 ~ 1.234),P = 0.401。趋化因子CCL2对肺鳞状细胞癌的IVW分析结果OR = 1.059,95%CI(0.931 ~ 1.205),P = 0.381。趋化因子CCL2对小细胞肺癌的IVW分析结果OR = 0.959, 95%CI(0.760 ~ 1.208),P = 0.720。 结论 趋化因子CCL2与肺癌没有直接因果关系。
刘梓燊 , 郑瑛瑛 , 袁梦琪 , 张甘霖 , 杨国旺 . 趋化因子CCL2与肺癌的因果关系:两样本孟德尔随机化研究[J]. 实用医学杂志, 2024 , 40(4) : 532 -536 . DOI: 10.3969/j.issn.1006-5725.2024.04.016
Objective To investigate whether chemokine CCL2 (also known as monocyte chemotactic protein 1 or MCP?1) has a causal relationship with lung cancer. Methods Genetic data of chemokine CCL2 and different pathological subtypes of lung cancer were extracted from genome?wide association studies (GWAS), and inverse?variance weighted (IVW) analysis was used as main analysis, while weighted median, simple model, MR?Egger regression, and weighted model were chosen as supplementary analyses. Sensitivity analyses were performed to verify the reliability of the data. Results The result of IVW analysis on chemokine CCL2 to lung adenocarcinoma was OR = 1.065, 95%CI (0.919 ~ 1.234), P = 0.401. The result of IVW analysis on chemokine CCL2 to squamous cell lung carcinoma was OR = 1.059, 95%CI (0.931 ~ 1.205), P = 0.381. The result of IVW analysis on chemokine CCL2 to small cell lung carcinoma was OR = 0.959, 95%CI (0.760 ~ 1.208), P = 0.720. Conclusions There is no direct causal relationship between chemokine CCL2 and lung cancer.
Key words: Mendelian randomization; monocyte chemokine; lung cancer; causality
| 1 | SUNG H, FERLAY J, SIEGEL R L, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. doi:10.3322/caac.21660 |
| 2 | CHEN T Y, FANG Y H, CHEN H L, et al. Impact of cooking oil fume exposure and fume extractor use on lung cancer risk in non-smoking Han Chinese women[J]. Sci Rep, 2020, 10(1): 6774. doi:10.1038/s41598-020-63656-7 |
| 3 | HUANG Y, ZHU M, JI M, et al. Air Pollution, Genetic Factors, and the Risk of Lung Cancer: A Prospective Study in the UK Biobank[J]. Am J Respir Crit Care Med, 2021, 204(7): 817-825. doi:10.1164/rccm.202011-4063oc |
| 4 | JOSEPH A M, ROTHMAN A J, ALMIRALL D, et al. Lung Cancer Screening and Smoking Cessation Clinical Trials. SCALE (Smoking Cessation within the Context of Lung Cancer Screening) Collaboration[J]. Am J Respir Crit Care Med, 2018, 197(2): 172-182. doi:10.1164/rccm.201705-0909ci |
| 5 | WANG M, HERBST R S, BOSHOFF C. Toward personalized treatment approaches for non-small-cell lung cancer[J]. Nat Med, 2021, 27(8): 1345-1356. doi:10.1038/s41591-021-01450-2 |
| 6 | BHUSAL R P, FOSTER S R, STONE M J. Structural basis of chemokine and receptor interactions: Key regulators of leukocyte recruitment in inflammatory responses[J]. Protein Sci, 2020, 29(2): 420-432. doi:10.1002/pro.3744 |
| 7 | 吴文娜, 陈晓红. MCP-1的表达与高血压病、动脉粥样硬化的关系[J]. 实用医学杂志, 2011, 27(15): 2876-2878. |
| 8 | LI L, LIU Y, ZHAN Y, et al. High levels of CCL2 or CCL4 in the tumor microenvironment predict unfavorable survival in lung adenocarcinoma[J]. Thoracic Cancer, 2018, 9(7): 775-784. doi:10.1111/1759-7714.12643 |
| 9 | BURGESS S, DAVEY SMITH G, DAVIES N M, et al. Guidelines for performing Mendelian randomization investigations: update for summer 2023[J]. Wellcome Open Res, 2019, 4: 186. doi:10.12688/wellcomeopenres.15555.1 |
| 10 | FOLKERSEN L, GUSTAFSSON S, WANG Q, et al. Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals[J]. Nat Metab, 2020, 2(10): 1135-1148. doi:10.1038/s42255-020-00287-2 |
| 11 | MCKAY J D, HUNG R J, HAN Y, et al. Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes[J]. Nat Genet, 2017, 49(7): 1126-1132. |
| 12 | PALMER T M, LAWLOR D A, HARBORD R M, et al. Using multiple genetic variants as instrumental variables for modifiable risk factors[J]. Stat Methods Med Res, 2012, 21(3): 223-242. doi:10.1177/0962280210394459 |
| 13 | XU M, WANG Y, XIA R, et al. Role of the CCL2-CCR2 signalling axis in cancer: Mechanisms and therapeutic targeting[J]. Cell Prolif, 2021, 54(10): e13115. doi:10.1111/cpr.13115 |
| 14 | FRAN?A C N, IZAR M C O, HORTêNCIO M N S, et al. Monocyte subtypes and the CCR2 chemokine receptor in cardiovascular disease[J]. Clin Sci (Lond), 2017, 131(12): 1215-1224. doi:10.1042/cs20170009 |
| 15 | LIU H, YANG Z, LU W, et al. Chemokines and chemokine receptors: A new strategy for breast cancer therapy[J]. Cancer Med, 2020, 9(11): 3786-3799. doi:10.1002/cam4.3014 |
| 16 | MOADAB F, KHORRAMDELAZAD H, ABBASIFARD M. Role of CCL2/CCR2 axis in the immunopathogenesis of rheumatoid arthritis: Latest evidence and therapeutic approaches[J]. Life Sci, 2021, 269: 119034. doi:10.1016/j.lfs.2021.119034 |
| 17 | YANG H, ZHANG Q, XU M, et al. CCL2-CCR2 axis recruits tumor associated macrophages to induce immune evasion through PD-1 signaling in esophageal carcinogenesis[J]. Mol Cancer, 2020, 19(1): 41. doi:10.1186/s12943-020-01165-x |
| 18 | DING M, HE S J, YANG J. MCP-1/CCL2 Mediated by Autocrine Loop of PDGF-BB Promotes Invasion of Lung Cancer Cell by Recruitment of Macrophages Via CCL2-CCR2 Axis[J]. J Interferon Cytokine Res, 2019, 39(4): 224-232. doi:10.1089/jir.2018.0113 |
| 19 | CHEN C H, SU L J, TSAI H T, et al. ELF-1 expression in nasopharyngeal carcinoma facilitates proliferation and metastasis of cancer cells via modulation of CCL2/CCR2 signaling[J]. Cancer Manag Res, 2019, 11: 5243-5254. doi:10.2147/cmar.s196355 |
| 20 | FENG L, QI Q, WANG P, et al. Serum level of CCL2 predicts outcome of patients with pancreatic cancer[J].Acta Gastroenterol Belg, 2020, 83(2): 295-299. |
| 21 | XIE M, LIN Z, JI X, et al. FGF19/FGFR4-mediated elevation of ETV4 facilitates hepatocellular carcinoma metastasis by upregulating PD-L1 and CCL2[J]. J Hepatol, 2023, 79(1): 109-125. doi:10.1016/j.jhep.2023.02.036 |
| 22 | YOSHIMURA T, LI C, WANG Y, et al. The chemokine monocyte chemoattractant protein-1/CCL2 is a promoter of breast cancer metastasis[J]. Cell Mol Immunol, 2023, 20(7): 714-738. doi:10.1038/s41423-023-01013-0 |
| 23 | WANG Y, ZHANG X, YANG L, et al. Blockade of CCL2 enhances immunotherapeutic effect of anti-PD1 in lung cancer[J]. J Bone Oncol, 2018, 11: 27-32. doi:10.1016/j.jbo.2018.01.002 |
| 24 | XU H, WANG J, AL-NUSAIF M, et al. CCL2 promotes metastasis and epithelial-mesenchymal transition of non-small cell lung cancer via PI3K/Akt/mTOR and autophagy pathways[J]. Cell Prolif, 2023: e13560. doi:10.1111/cpr.13560 |
| 25 | YASUI H, KAJIYAMA H, TAMAUCHI S, et al. CCL2 secreted from cancer-associated mesothelial cells promotes peritoneal metastasis of ovarian cancer cells through the P38-MAPK pathway[J]. Clin Exp Metastasis, 2020, 37(1): 145-158. doi:10.1007/s10585-019-09993-y |
| 26 | WANG T, ZHAN Q, PENG X, et al. CCL2 influences the sensitivity of lung cancer A549 cells to docetaxel[J]. Oncol Lett, 2018, 16(1): 1267-1274. |
| 27 | KALBASI A, KOMAR C, TOOKER G M, et al. Tumor-Derived CCL2 Mediates Resistance to Radiotherapy in Pancreatic Ductal Adenocarcinoma[J]. Clin Cancer Res, 2017, 23(1): 137-148. doi:10.1158/1078-0432.ccr-16-0870 |
| 28 | SALCEDO R, PONCE M L, YOUNG H A, et al. Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression[J]. Blood, 2000, 96(1): 34-40. doi:10.1182/blood.v96.1.34.013a49_34_40 |
| 29 | BONAPACE L, COISSIEUX M M, WYCKOFF J, et al. Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis[J]. Nature, 2014, 515(7525): 130-133. doi:10.1038/nature13862 |
| 30 | WEI C, YANG C, WANG S, et al. Crosstalk between cancer cells and tumor associated macrophages is required for mesenchymal circulating tumor cell-mediated colorectal cancer metastasis[J]. Mol Cancer, 2019, 18(1): 64. doi:10.1186/s12943-019-0976-4 |
| 31 | CHEN X, YANG M, YIN J, et al. Tumor-associated macrophages promote epithelial-mesenchymal transition and the cancer stem cell properties in triple-negative breast cancer through CCL2/AKT/β-catenin signaling[J]. Cell Commun Signal, 2022, 20(1): 92. doi:10.1186/s12964-022-00888-2 |
| 32 | LI X, YAO W, YUAN Y, et al. Targeting of tumour-infiltrating macrophages via CCL2/CCR2 signalling as a therapeutic strategy against hepatocellular carcinoma[J]. Gut, 2017, 66(1): 157-167. doi:10.1136/gutjnl-2015-310514 |
| 33 | MOISAN F, FRANCISCO E B, BROZOVIC A, et al. Enhancement of paclitaxel and carboplatin therapies by CCL2 blockade in ovarian cancers[J]. Mol Oncol 2014, 8(7): 1231-1239. doi:10.1016/j.molonc.2014.03.016 |
| 34 | QIAN B Z, LI J, ZHANG H, et al. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis[J]. Nature, 2011, 475(7355): 222-225. doi:10.1038/nature10138 |
| 35 | CHEN S, SHAO F, ZENG J, et al. Cullin-5 deficiency orchestrates the tumor microenvironment to promote mammary tumor development through CREB1-CCL2 signaling[J]. Sci Adv, 2023, 9(3): eabq1395. doi:10.1126/sciadv.abq1395 |
| 36 | MA W J, LI Z H, WU Z R, et al. PI3K-CCL2-CCR2-MDSCs axis: A potential pathway for tumor Clostridia-promoted CD 8+ T lymphocyte infiltration in bile tract cancers[J]. Neoplasia 2023, 43: 100920. doi:10.1016/j.neo.2023.100920 |
| 37 | HU W M, LI M, NING J Z, et al. FAM171B stabilizes vimentin and enhances CCL2-mediated TAM infiltration to promote bladder cancer progression[J]. J Exp Clin Cancer Res, 2023, 42: 290. doi:10.1186/s13046-023-02860-5 |
| 38 | ZHOU C, WENG J, LIU C, et al. Disruption of SLFN11 Deficiency-Induced CCL2 Signaling and Macrophage M2 Polarization Potentiates Anti-PD-1 Therapy Efficacy in Hepatocellular Carcinoma[J]. Gastroenterology, 2023, 164(7): 1261-1278. doi:10.1053/j.gastro.2023.02.005 |
| 39 | KO K P, HUANG Y, ZHANG S, et al. Key Genetic Determinants Driving Esophageal Squamous Cell Carcinoma Initiation and Immune Evasion[J]. Gastroenterology, 2023, 165(3): 613-628.e20. doi:10.1053/j.gastro.2023.05.030 |
| 40 | PAN B, WAN T, ZHOU Y, et al. The MYBL2-CCL2 axis promotes tumor progression and resistance to anti-PD-1 therapy in ovarian cancer by inducing immunosuppressive macrophages[J]. Cancer Cell Int, 2023, 23(1): 248. doi:10.1186/s12935-023-03079-2 |
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