ADAP2基因与肺鳞癌患者预后及肿瘤微环境免疫细胞浸润的关联研究

陈峥; 向颖; 邬娜; 夏婷婷; 单亦凡; 谢薇佳; 许斌; 袁志权; 胡琴; 贾潇岳; 吴龙; 李亚斐

doi:10.16016/j.2097-0927.202110066

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ADAP2基因与肺鳞癌患者预后及肿瘤微环境免疫细胞浸润的关联研究

基础医学 | 更新时间：2026-01-09

- ADAP2基因与肺鳞癌患者预后及肿瘤微环境免疫细胞浸润的关联研究
- Association of ADAP2 gene with prognosis and immune infiltration in tumor microenvironment in patients with lung squamous cell carcinoma
- 陆军军医大学学报 2022年44卷第4期页码：337-345
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)军事预防医学系军队流行病学教研室
- 作者简介：
  
  [李亚斐，E-mail: liyafei2008@hotmail.com LI Yafei, E-mail: liyafei2008@hotmail.com
- 基金信息：
  
  国家自然科学基金面上项目(81871896)
- DOI：10.16016/j.2097-0927.202110066
  中图分类号： R394.3;R730.7;R734.2
- 收稿：2021-10-13，
  
  修回：2021-12-01，
  
  纸质出版：2022-02-28
- 稿件说明：
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陈峥, 向颖, 邬娜, 等. ADAP2基因与肺鳞癌患者预后及肿瘤微环境免疫细胞浸润的关联研究[J]. 陆军军医大学学报, 2022,44(4):337-345.

Zheng CHEN, Ying XIANG, Na WU, et al. Association of ADAP2 gene with prognosis and immune infiltration in tumor microenvironment in patients with lung squamous cell carcinoma[J]. Journal of Army Medical University, 2022, 44(4): 337-345.
陈峥, 向颖, 邬娜, 等. ADAP2基因与肺鳞癌患者预后及肿瘤微环境免疫细胞浸润的关联研究[J]. 陆军军医大学学报, 2022,44(4):337-345. DOI： 10.16016/j.2097-0927.202110066.

Zheng CHEN, Ying XIANG, Na WU, et al. Association of ADAP2 gene with prognosis and immune infiltration in tumor microenvironment in patients with lung squamous cell carcinoma[J]. Journal of Army Medical University, 2022, 44(4): 337-345. DOI： 10.16016/j.2097-0927.202110066.

摘要

目的

分析ADAP2基因与肺鳞癌患者预后及其与肿瘤微环境免疫细胞浸润的关联。

方法

下载TCGA(The Cancer Genome Atlas)数据库肺鳞癌患者临床信息和癌组织ADAP2基因转录水平，运用KM生存曲线和Cox比例风险模型分析ADAP2基因和患者预后的关联；采用xCell数据库分析ADAP2基因表达和肿瘤微环境免疫浸润的关系；利用免疫荧光双染实验观察ADAP2蛋白与M2型巨噬细胞标志物CD163的空间共定位。

结果

多因素Cox分析结果显示，ADAP2表达是肺鳞癌患者独立的预后因素，其高表达与肺鳞癌患者不良预后密切相关(

=1.533，95%

: 1.139~2.064，

=0.005)。ADAP2基因与肿瘤微环境评分呈正相关(

=0.609，95%

: 0.550~0.661，

＜0.001)，与免疫评分也同样呈正相关(

=0.596，95%

: 0.536~0.650，

＜0.001)。ADAP2基因与肺鳞癌单核吞噬细胞系统(巨噬细胞、巨噬细胞M1、巨噬细胞M2、单核细胞)的浸润呈高度正相关(

=0.737、0.718、0.603、0.631，

＜0.001)。ADAP2与CD163存在共定位，主要表达于细胞膜。

结论

ADAP2有望成为预测肺鳞癌患者预后和免疫治疗效果的潜在生物标志物。

Abstract

Objective

To investigate the correlation between ADAP2 gene and immune infiltration in tumor microenvironment in lung squamous cell carcinoma (LUSC)

and to explore the prognostic values of ADAP2 in patients with LUSC.

Methods

The clinical information of patients with LUSC as well as the data of ADAP2 mRNA levels in cancer tissues were downloaded from The Cancer Genome Atlas (TCGA) database. The association between ADAP2 gene and prognosis of patients was subsequently analyzed using Kaplan-Meier survival curve and Cox risk model analyses. xCell database was adopted to analyze the correlation of ADAP2 expression with immune infiltration in tumor microenvironment. Immunofluorescence double-staining test was employed to observe the co-localization of ADAP2 protein and CD163 (a specific biomarker of M2 macrophage).

Results

Multivariate Cox analysis showed that the expression of ADAP2 was an independent prognostic factor for LUSC patients

and its high expression was closely associated with the poor prognosis of patients (

=1.533

95%

: 1.139~2.064

=0.005). xCell analysis indicated that ADAP2 gene was positively correlated with both the tumor microenvironment score (

=0.609

95%

: 0.550~0.661

0.001)

and the immune infiltration score (

=0.596

95%

: 0.536~0.650

0.001)

and the expression of ADAP2 also showed a high positive association with mononuclear phagocyte system (macrophage

macrophage M1

macrophage M2 and monocyte) in LUSC (

=0.737

0.718

0.603 and 0.631

respectively

0.001). Moreover

ADAP2 presented co-localization with CD163 and was mainly expressed in the cell membrane.

Conclusion

ADAP2 can act as a potential biomarker for predicting prognosis and evaluating the efficacy of immunotherapy in LUSC.

关键词

Keywords

references

SUNG H, FERLAY J, SIEGEL R L, et al . Global cancer statistics2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J ] . CA A Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.

THORSTEINSSON H, ALEXANDERSSON A, OSKARSDOTTIR G N, et al . Resection rate and outcome of pulmonary resections for non-small-cell lung cancer: a nationwide study from Iceland[J ] . J Thorac Oncol, 2012, 7(7): 1164-1169. DOI: 10.1097/jto.0b013e318252d022.

HAMID O, SCHMIDT H, NISSAN A, et al . A prospective phase Ⅱ trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma[J ] . J Transl Med, 2011, 9: 204. DOI: 10.1186/1479-5876-9-204.

CHEN P L, ROH W, REUBEN A, et al . Analysis of immune signatures in longitudinal tumor samples yields insight into biomarkers of response and mechanisms of resistance to immune checkpoint blockade[J ] . Cancer Discov, 2016, 6(8): 827-837. DOI: 10.1158/2159-8290.cd-15-1545.

JOHNSON D B, ESTRADA M V, SALGADO R, et al . Melanoma-specific MHC-Ⅱ expression represents atumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy[J ] . Nat Commun, 2016, 7: 10582. DOI: 10.1038/ncomms10582.

BIST P, KIM S S Y, PULLOOR N K, et al . ArfGAP domain-containing protein 2 (ADAP2) integrates upstream and downstream modules of RIG-Ⅰ signaling and facilitates type Ⅰ interferon production[J ] . Mol Cell Biol, 2017, 37(6): e00537-16. DOI: 10.1128/MCB.00537-16.

ZHANG M, WANG X, CHEN X, et al . Prognostic value of astemness index-associated signature in primary lower-grade glioma[J ] . Front Genet, 2020, 11: 441. DOI: 10.3389/fgene.2020.00441.

BUENO R, RICHARDS W G, HARPOLE D H, et al . Multi-institutional prospective validation of prognostic mRNA signatures in early stage squamous lung cancer (alliance)[J ] . J Thorac Oncol, 2020, 15(11): 1748-1757. DOI: 10.1016/j.jtho.2020.07.005.

ARAN D, HU Z, BUTTE A J. xCell: digitally portraying the tissue cellular heterogeneity landscape[J]. Genome Biol, 2017, 18(1): 220. DOI: 10.1186/s13059-017-1349-1.

段怡平, 陈梁玥, 柳家翠, 等. 基于TCGA数据库分析PFKFB4在肝细胞癌的临床意义及分子机制[J]. 分子诊断与治疗杂志, 2021, 13(1): 25-29. DOI: 10.19930/j.cnki.jmdt.2021.01.007.

DUAN Y P, CHEN L Y, LIU J C, et al . Analysis of the clinical significance and molecular mechanism of PFKFB4in hepatocellular carcinoma based on the TCGA database[J ] . J Mol Diagn Ther, 2021, 13(1): 25-29. DOI: 10.19930/j.cnki.jmdt.2021.01.007.

SZKLARCZYK D, GABLEA L, NASTOU K C, et al . The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets[J ] . Nucleic Acids Res, 2021, 49(D1): D605-D612. DOI: 10.1093/nar/gkaa1074.

陈梦雷, 袁帅, 周玫余, 等. 长链非编码RNA SFTA1P在肺腺癌中的表达及预后预测研究[J]. 第三军医大学学报, 2020, 42(21): 2075-2080, 2115. DOI: 10.16016/j.1000-5404.202005271.

CHEN M L, YUAN S, ZHOU M Y, et al . Expression of long non-coding RNA SFTA1P in lung adenocarcinoma and its predictive value for prognosis[J ] . J Third Mil Med Univ, 2020, 42(21): 2075-2080, 2115. DOI: 10.16016/j.1000-5404.202005271.

CAMP R L, DOLLED-FILHART M, RIMM D L. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-pointoptimization[J]. Clin Cancer Res, 2004, 10(21): 7252-7259. DOI: 10.1158/1078-0432.ccr-04-0713.

SHU Q, LENNEMANN N J, SARKAR S N, et al . ADAP2 is an interferon stimulated gene that restricts RNA virus entry[J ] . PLoS Pathog, 2015, 11(9): e1005150. DOI: 10.1371/journal.ppat.1005150.

LIU X, WU S, YANG Y, et al . The prognostic landscape of tumor-infiltrating immune cell and immunomodulators in lung cancer[J ] . Biomed Pharmacother, 2017, 95: 55-61. DOI: 10.1016/j.biopha.2017.08.003.

CHEN D S, MELLMAN I. Elements of cancer immunity and the cancer-immune set point[J]. Nature, 2017, 541(7637): 321-330. DOI: 10.1038/nature21349.

BINGLE L, BROWN N J, LEWIS C E. The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies[J]. J Pathol, 2002, 196(3): 254-265. DOI: 10.1002/path.1027.

YEUNG O W, LO C M, LING C C, et al . Alternatively activated (M2) macrophages promote tumour growth and invasiveness in hepatocellular carcinoma[J ] . J Hepatol, 2015, 62(3): 607-616. DOI: 10.1016/j.jhep.2014.10.029.

SCHMALL A, AL-TAMARI H M, HEROLD S, et al . Macrophage and cancer cell cross-talk via CCR2 and CX3CR1 is a fundamental mechanism driving lung cancer[J ] . Am J Respir Crit Care Med, 2015, 191(4): 437-447. DOI: 10.1164/rccm.201406-1137oc..

ROUMENINA L T, DAUGAN M V, NOÉ R, et al . Tumor cells hijack macrophage-produced complement C1q to promote tumor growth[J ] . Cancer Immunol Res, 2019, 7(7): 1091-1105. DOI: 10.1158/2326-6066.cir-18-0891.

STEIDL C, LEE T, SHAH S P, et al . Tumor-associated macrophages and survival in classic Hodgkin's lymphoma[J ] . N Engl J Med, 2010, 362(10): 875-885. DOI: 10.1056/nejmoa0905680.

PAWELEK J M. Tumour-cell fusion as a source of myeloid traits in cancer[J]. Lancet Oncol, 2005, 6(12): 988-993. DOI: 10.1016/s1470-2045(05)70466-6.

FRANCIAN A, MANN K, KULLBERG M. Complement C3-dependent uptake of targeted liposomes into human macrophages, B cells, dendritic cells, neutrophils, and MDSCs[J]. Int J Nanomed, 2017, 12: 5149-5161. DOI: 10.2147/ijn.s138787.

YIN Z, ZHOU Y, MA T, et al . Down-regulated lncRNA SBF2-AS1 in M2 macrophage- derived exosomes elevates miR-122-5p to restrict XIAP, thereby limiting pancreatic cancer development[J ] . J Cell Mol Med, 2020, 24(9): 5028-5038. DOI: 10.1111/jcmm.15125.

LAMBERTI M J, MENTUCCI F M, ROSELLI E, et al . Photodynamic modulation of type 1 interferon pathway on melanoma cells promotes dendritic cell activation[J ] . Front Immunol, 2019, 10: 2614. DOI: 10.3389/fimmu.2019.02614.

GARRIS C S, PITTET M J. ER stress in dendritic cells promotes cancer[J]. Cell, 2015, 161(7): 1492-1493. DOI: 10.1016/j.cell.2015.06.006.

HOOS A. Development of immuno-oncology drugs—from CTLA4 to PD1 to the next generations[J]. Nat Rev Drug Discov, 2016, 15(4): 235-247. DOI: 10.1038/nrd.2015.35.

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