Expression and clinical significance of CXC motif chemokine ligand 13 in triple-negative breast cancer
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摘要:目的
探讨趋化因子配体13(CXCL13)表达水平对三阴性乳腺癌(TNBC)患者总体生存期(OS)的影响,分析CXCL13与肿瘤浸润性淋巴细胞(TIL)浸润程度及常见免疫检查点表达的关系。
方法下载癌症基因组图谱数据库中TNBC患者的转录组测序结果及临床资料数据,分析CXCL13表达与TNBC患者OS的关系。应用基因集富集分析(GSEA)软件挖掘CXCL13在TNBC中的生物学功能; 应用肿瘤免疫评估资源(TIMER)数据库分析CXCL13与TNBC中TIL浸润程度及常见免疫检查点表达量的相关性。
结果CXCL13在TNBC中呈显著高表达(P < 0.001),其表达量与患者OS具有显著相关性(P < 0.05)。GSEA结果显示, CXCL13在TNBC中高表达可使关键免疫相关通路活化。TIMER数据库分析显示, CXCL13与TNBC中TIL的浸润程度及常见免疫检查点程序性死亡受体1、程序性死亡受体-配体1及细胞毒性T淋巴细胞相关蛋白4的表达量呈显著正相关(P < 0.001)。
结论CXCL13是TNBC患者预后的预测因子,或可在TNBC的免疫治疗中发挥重要作用。
Abstract:ObjectiveTo explore the effect of the expression level of CXC motif chemokine ligand 13 (CXCL13) on the overall survival (OS) of patients with triple-negative breast cancer (TNBC), and to analyze the relationships of CXCL13 with infiltration degree of tumor-infiltrating lymphocytes (TIL) and the expression of common immune checkpoints.
MethodsThe transcriptome sequencing results and clinical data of TNBC patients in the cancer Genome Atlas database were downloaded, and the relationship between CXCL13 expression and OS in TNBC patients was analyzed. The biological function of CXCL13 in TNBC was excavated by Gene-set Enrichment Analysis (GSEA); the Tumor Immune Estimation Resource (TIMER) database was used to analyze the correlations of the expression level of CXCL13 with TIL infiltration degree and the expression of common immune checkpoints in TNBC.
ResultsCXCL13 was significantly highly expressed in TNBC (P < 0.001), and its expression level was significantly correlated with OS of patients (P < 0.05). Results of GSEA showed that the high expression of CXCL13 in TNBC was able to activate key immune-related pathways. TIMER database analysis showed that CXCL13 was significantly positively correlated with the infiltration degree of TIL and the expressions of common immune checkpoints such as programmed death receptor 1, programmed death receptor ligand 1 and cytotoxic T lymphocyte associated protein 4 at in TNBC patients (P < 0.001).
ConclusionCXCL13 is a prognostic factor for patients with TNBC, and may play an important role in immunotherapy of TNBC.
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表 1 TNBC患者CXCL13表达与临床病理资料的关系
临床病理资料 分类 n CXCL13表达水平 χ2 P 低表达组(n=66) 高表达组(n=66) 年龄 ≤60岁 91 46 45 0.005 0.943 >60岁 41 20 21 肿瘤大小 ≤2 cm 35 14 21 1.768 0.184 >2 cm 97 52 45 淋巴结转移 无 84 36 48 4.161 0.041 有 48 30 18 TNM分期 Ⅰ期 24 7 17 5.471 0.019 其他 108 59 49 -
[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] 陈怡萌. 晚期三阴性乳腺癌含铂治疗的真实世界研究及疗效预测因子的探索性研究[D]. 北京: 北京协和医学院, 2021. [3] 刘迅舟. ALDH1A3靶向小分子YD1701抑制三阴性乳腺癌转移的初步研究[D]. 重庆: 西南大学, 2020. [4] 朱洪宇, 史志敏. 微小RNA-338-3p调控信号转导和转录激活因子1对表皮生长因子受体酪氨酸激酶抑制剂耐药肺癌细胞株PC-9/GR中程序性死亡配体1表达和细胞凋亡的影响[J]. 实用临床医药杂志, 2022, 26(4): 100-105. https://www.cnki.com.cn/Article/CJFDTOTAL-XYZL202204023.htm [5] TARANTINO P, ANTONARELLI G, ASCIONE L, et al. Investigational immunomodulatory drugs for enhancement of triple negative breast cancer (TNBC) immunotherapy: early phase development[J]. Expert Opin Investig Drugs, 2022, 31(6): 499-513. doi: 10.1080/13543784.2021.1972968
[6] NAGARSHETH N, WICHA M S, ZOU W P. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy[J]. Nat Rev Immunol, 2017, 17(9): 559-572. doi: 10.1038/nri.2017.49
[7] LACALLE R A, BLANCO R, CARMONA-RODRÍGUEZ L, et al. Chemokine receptor signaling and the hallmarks of cancer[J]. Int Rev Cell Mol Biol, 2017, 331: 181-244.
[8] HUSSAIN M, ADAH D, TARIQ M, et al. CXCL13/CXCR5 signaling axis in cancer[J]. Life Sci, 2019, 227: 175-186. doi: 10.1016/j.lfs.2019.04.053
[9] COSGROVE J, NOVKOVIC M, ALBRECHT S, et al. B cell zone reticular cell microenvironments shape CXCL13 gradient formation[J]. Nat Commun, 2020, 11(1): 3677. doi: 10.1038/s41467-020-17135-2
[10] LITCHFIELD K, READING J L, PUTTICK C, et al. Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition[J]. Cell, 2021, 184(3): 596-614, e14. doi: 10.1016/j.cell.2021.01.002
[11] LI Y X, WANG S M, LI C Q. Four-lncRNA immune prognostic signature for triple-negative breast cancer Running title: immune lncRNAs predict prognosis of TNBC[J]. Math Biosci Eng, 2021, 18(4): 3939-3956. doi: 10.3934/mbe.2021197
[12] KEENAN T E, TOLANEY S M. Role of immunotherapy in triple-negative breast cancer[J]. J Natl Compr Canc Netw, 2020, 18(4): 479-489. doi: 10.6004/jnccn.2020.7554
[13] 李洋, 蒋立峰, 孙旭, 等. 免疫检查点抑制剂在表皮生长因子受体突变非小细胞肺癌中的研究进展[J]. 实用临床医药杂志, 2022, 26(2): 142-148. https://www.cnki.com.cn/Article/CJFDTOTAL-XYZL202202029.htm [14] CORTES J, CESCON D W, RUGO H S, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial[J]. Lancet, 2020, 396(10265): 1817-1828. doi: 10.1016/S0140-6736(20)32531-9
[15] YARCHOAN M, HOPKINS A, JAFFEE E M. Tumor mutational burden and response rate to PD-1 inhibition[J]. N Engl J Med, 2017, 377(25): 2500-2501. doi: 10.1056/NEJMc1713444
[16] NISHINO M, RAMAIYA N H, HATABU H, et al. Monitoring immune-checkpoint blockade: response evaluation and biomarker development[J]. Nat Rev Clin Oncol, 2017, 14(11): 655-668. doi: 10.1038/nrclinonc.2017.88
[17] ZARETSKY J M, GARCIA-DIAZ A, SHIN D S, et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma[J]. N Engl J Med, 2016, 375(9): 819-829. doi: 10.1056/NEJMoa1604958
[18] 王红卫, 赵阳, 张帆, 等. 肿瘤浸润淋巴细胞与三阴性乳腺癌预后关系的系统评价[J]. 国际外科学杂志, 2021, 48(9): 609-617, F3. [19] 陈碧薇. 三阴乳腺癌免疫检查点抑制剂联合化疗有效性及安全性的Meta分析[D]. 张家口: 河北北方学院, 2021. -
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