>
网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
基于生物信息学分析WNT7B基因在肺腺癌中的表达及其临床意义
作者:卫斐然1  秦伟卓2  费高强2  张学宁3 
单位:1. 东南大学 附属中大医院, 江苏 南京 210009;
2. 东南大学 公共卫生学院, 江苏 南京 210009;
3. 江苏省卫生健康发展研究中心, 江苏 南京 210000
关键词:WNT7B基因 肺腺癌 预后 免疫浸润 
分类号:R734.2
出版年·卷·期(页码):2023·42·第六期(820-830)
摘要:

目的:基于生物信息学分析WNT7B基因在肺腺癌(LUAD)中的表达及其临床意义。方法:应用生物信息学方法评价WNT7B在LUAD中的诊断和预后预测价值。通过TCGA、GEO数据库研究WNT7B基因在肺癌中表达情况,并分析WNT7B基因在肺癌和非癌组织中表达差异及其表达与生存率、免疫细胞浸润之间的关系。应用STRING数据库筛选共表达基因并构建调控网络,将共表达基因进行基因本体论(GO)以及京东基因和基因组(KEGG)富集分析,同时应用cBioportal探究WNT7B基因突变对肺癌患者生存期的影响。结果:与正常肺组织相比,LUAD组织中WNT7B基因表达水平明显升高(P<0.01),WNT7B基因作为标志物的灵敏度为0.628。K-M生存分析显示,高表达WNT7B组预后较差(P<0.05)。GSEA揭示了5条与WNT7B基因相关的信号通路,WNT7B基因突变的LUAD患者总生存期(P=0.035 8)的预后预测作用不佳。此外,还发现WNT7B基因表达与免疫显著相关。结论:WNT7B基因有望成为LUAD诊断、预后评估和治疗的新靶点,但仍须进一步开展临床相关研究。

Objective: To analyze of the expression and clinical significance of WNT7B gene in lung adenocarcinoma(LUAD) based on bioinformatics. Methods: Bioinformatics methods were used to evaluate the diagnostic and prognostic value of WNT7B gene in LUAD. The expression of WNT7B gene in lung cancer was studied by TCGA and GEO databases, and the expression difference of WNT7B gene in lung cancer and non-cancer tissues and its relationship with survival rate and immune cell infiltration were analyzed. The STRING database was used to screen co-expressed genes and construct regulatory networks. The co-expressed genes were subjected to gene ontology(GO) and Jingdong gene and genome(KEGG) enrichment analysis. At the same time, cBioportal was used to explore the effect of WNT7B gene mutation on the survival of lung cancer patients. Results: Compared with normal lung tissue, the expression level of WNT7B gene in LUAD tissue was significantly increased(P<0.01), and the sensitivity of WNT7B gene as a marker was 0.628. K-M survival analysis showed that the high expression of WNT7 B group had a poor prognosis(P<0.05). GSEA revealed five WNT7B-related signaling pathways. The prognosis of LUAD patients with WNT7B gene mutation was poor(P=0.035 8). In addition, it was also found that WNT7B expression was significantly associated with immunity. Conclusion: WNT7B gene can be used as a prognostic and diagnostic biomarker, which provides a deeper perspective for the treatment of LUAD and the development of prognostic markers.

参考文献:

[1] IMIELINSKI M,BERGER A H,HAMMERMAN P S,et al.Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing[J].Cell,2012,150(6):1107-1120.
[2] ABDULJABBAR K,RAZA S E A,ROSENTHAL R,et al.Geospatial immune variability illuminates differential evolution of lung adenocarcinoma[J].Nat Med,2020,26(7):1054-1062.
[3] HERBST R S,MORGENSZTERN D,BOSHOFF C.The biology and management of non-small cell lung cancer[J].Nature,2018,553(7689):446-454.
[4] HIRSCH F R,SCAGLIOTTI G V,MULSHINE J L,et al.Lung cancer:current therapies and new targeted treatments[J].Lancet,2017,389(10066):299-311.
[5] NUSSE R,CLEVERS H.Wnt/β-catenin signaling,disease,and emerging therapeutic modalities[J].Cell,2017,169(6):985-999.
[6] PACHECO-PINEDO E C,DURHAM A C,STEWART K M,et al.Wnt/β-catenin signaling accelerates mouse lung tumorigenesis by imposing an embryonic distal progenitor phenotype on lung epithelium[J].J Clin Invest,2011,121(5):1935-1945.
[7] PARR B A,CORNISH V A,CYBULSKY M I,et al.Wnt7b regulates placental development in mice[J].Dev Biol,2001,237(2):324-332.
[8] SHU W,JIANG Y Q,LU M M,et al.Wnt7b regulates mesenchymal proliferation and vascular development in the lung[J].Development,2002,129(20):4831-4842.
[9] RAJAGOPAL J,CARROLL T J,GUSEH J S,et al.Wnt7b stimulates embryonic lung growth by coordinately increasing the replication of epithelium and mesenchyme[J].Development,2008,135(9):1625-1634.
[10] ZHANG Z,XU Y,ZHAO C.Fzd7/Wnt7b signaling contributes to stemness and chemoresistance in pancreatic cancer[J].Cancer Med,2021,10(10):3332-3345.
[11] HAN J,DENG X,SUN R,et al.GPI is a prognostic biomarker and correlates with immune infiltrates in lung adenocarcinoma[J].Front Oncol,2021,11:752642.
[12] 易宣洪,黄晓智,王静,等.肺癌组织miR-29a-3p、TRIB2水平及其与患者病理特征、预后的关系[J].东南大学学报(医学版),2023,42(3):405-411.
[13] JIN C Y,DU L,NUERLAN A H,et al.High expression of RRM2 as an independent predictive factor of poor prognosis in patients with lung adenocarcinoma[J].Aging(Albany NY),2020,13(3):3518-3535.
[14] LI H,GUO L,CAI Z.TCN1 is a potential prognostic biomarker and correlates with immune infiltrates in lung adenocarcinoma[J].World J Surg Oncol,2022,20(1):83.
[15] LIU X S,ZHOU L M,YUAN L L,et al.NPM1 is a prognostic biomarker involved in immune infiltration of lung adenocarcinoma and associated with m6A modification and glycolysis[J].Front Immunol,2021,12:724741.
[16] MEADOR C B,HATA A N.Acquired resistance to targeted therapies in NSCLC:updates and evolving insights[J].Pharmacol Ther,2020,210:107522.
[17] RILEY R S,JUNE C H,LANGER R,et al.Delivery technologies for cancer immunotherapy[J].Nat Rev Drug Discov,2019,18(3):175-196.
[18] BAGCHI S,YUAN R,ENGLEMAN E G.Immune checkpoint inhibitors for the treatment of cancer:clinical impact and mechanisms of response and resistance[J].Annu Rev Pathol,2021,16:223-249.
[19] WU F,LI B,HU X,et al.Wnt7b inhibits osteoclastogenesis via AKT activation and glucose metabolic rewiring[J].Front Cell Dev Biol,2021,9:771336.
[20] FENG B,PEI J,GU S.Wnt7b:is it an important factor in the bone formation process after calvarial damage?[J].J Clin Med,2023,12(3):800.
[21] BOULTER L,GUEST R V,KENDALL T J,et al.WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited[J].J Clin Invest,2015,125(3):1269-1285.
[22] 陈奕鹤,马立文,殷旭峰,等.WNT7b促进黑素瘤细胞的迁移、侵袭与上皮间质转化[J].南京医科大学学报(自然科学版),2021,41(9):1322-1328.
[23] JIANG S,LI Q,LIU Y,et al.Activation of WNT7b autocrine eases metastasis of colorectal cancer via epithelial to mesenchymal transition and predicts poor prognosis[J].BMC Cancer,2021,21(1):180.
[24] CHEN S,DING H,WANG K,et al.Inhibition of Wnt7b reduces the proliferation,invasion,and migration of colorectal cancer cells[J].Mol Biol Rep,2023,50(2):1415-1424.
[25] NA L,WANG Z,BAI Y,et al.WNT7B represses epithelial-mesenchymal transition and stem-like properties in bladder urothelial carcinoma[J].Biochim Biophys Acta Mol Basis Dis,2022,1868(1):166271.
[26] MA S,ZHOU B,YANG Q,et al.A transcriptional regulatory loop of master regulator transcription factors,PPARG,and fatty acid synthesis promotes esophageal adenocarcinoma[J].Cancer Res,2021,81(5):1216-1229.
[27] CHO J K,LEE G J,YI K I,et al.Development and external validation of nomograms predictive of response to radiation therapy and overall survival in nasopharyngeal cancer patients[J].Eur J Cancer,2015,51(10):1303-1311.
[28] LI J,LIU Y,YAN Z,et al.A nomogram predicting pulmonary metastasis of hepatocellular carcinoma following partial hepatectomy[J].Br J Cancer,2014,110(5):1110-1117.
[29] GUO Y,SONG J,WANG Y,et al.Concurrent genetic alterations and other biomarkers predict treatment efficacy of EGFR-TKIs in EGFR-mutant non-small cell lung cancer:a review[J].Front Oncol,2020,10:610923.
[30] HSU L W,HUANG K H,CHEN M H,et al.Genetic alterations in gastric cancer patients according to sex[J].Aging(Albany NY),2020,13(1):376-388.
[31] CHEN L,CHEN F,LI J,et al.CAR-T cell therapy for lung cancer:potential and perspective[J].Thorac Cancer,2022,13(7):889-899.
[32] WANG S S,LIU W,LY D,et al.Tumor-infiltrating B cells:their role and application in anti-tumor immunity in lung cancer[J].Cell Mol Immunol,2019,16(1):6-18.
[33] ZHOU F,QIAO M,ZHOU C.The cutting-edge progress of immune-checkpoint blockade in lung cancer[J].Cell Mol Immunol,2021,18(2):279-293.
[34] ZHANG Q,TANG L,ZHOU Y,et al.Immune checkpoint inhibitor-associated pneumonitis in non-small cell lung cancer:current understanding in characteristics,diagnosis,and management[J].Front Immunol,2021,12:663986.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 400699 位访问者


copyright ©《东南大学学报(医学版)》编辑部
联系电话:025-83272481 83272483
电子邮件:
bjb@pub.seu.edu.cn

苏ICP备09058364