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:
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.
Association of ADAP2 gene with prognosis and immune infiltration in tumor microenvironment in patients with lung squamous cell carcinoma
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。
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
2
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
2
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 (
HR
=1.533
95%
CI
: 1.139~2.064
P
=0.005). xCell analysis indicated that ADAP2 gene was positively correlated with both the tumor microenvironment score (
r
=0.609
95%
CI
: 0.550~0.661
P
<
0.001)
and the immune infiltration score (
r
=0.596
95%
CI
: 0.536~0.650
P
<
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 (
r
=0.737
0.718
0.603 and 0.631
respectively
P
<
0.001). Moreover
ADAP2 presented co-localization with CD163 and was mainly expressed in the cell membrane.
Conclusion
2
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.
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.
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.
Immunosuppressive microenvironment of TGIF1-overexpressing gastric cancers and its clinical significance
Relationship of base excision repair pathway-related proteins with immune cell infiltration and prognosis in small cell lung cancer
A novel estrogen receptor expression stratification (low/moderate/high) based on Chinese population provides more accurate prognosis prediction for HR+/HER2- early breast cancer patients
Impact of molecular heterogeneity of NPM1 mutations on prognosis of acute myeloid leukemia: a clinical report of 86 cases
Association of 5-factor modified frailty index and controlling nutritional status score with overall survival in patients with unresectable hepatocellular carcinoma undergoing interventional therapy
Related Author
TONG Huyun
CHEN Xu
ZHANG Wenjie
WANG Tao
LI Xianfeng
QIU Qiu
WANG Bin
LI Chaofan
Related Institution
Department of Gastroenterology, Chongqing Hechuan District People’s Hospital
School of Medicine, Chongqing University
Chongqing Key Laboratory of Precision Prevention and Treatment for Digestive System Tumors, Department of Gastroenterology, Army Medical Center of PLA/Daping Hospital of Third Military Medical University
Cancer Center, Army Medical Center of PLA/Daping Hospital of Third Military Medical University
Department of Breast and Thyroid Surgery, First Affiliated Hospital, Army Medical University (Third Military Medical University)