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WDR76表达与肺腺癌生存结局及免疫浸润的相关性

The correlation of WDR76 expression with survival outcomes and immune infiltrates in lung adenocarcinoma.

作者信息

Fang Likui, Yu Guocan, Yu Wenfeng, Chen Gang, Ye Bo

机构信息

Department of Thoracic Surgery, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

PeerJ. 2021 Oct 4;9:e12277. doi: 10.7717/peerj.12277. eCollection 2021.

Abstract

BACKGROUND

WD repeat domain 76 (WDR76) is a predicted member of the WD40-repeat-containing domain superfamily and possibly involves in various biological processes, but its function in cancers is poorly characterized. This study aimed to evaluate the role of WDR76 in the prognosis and immune infiltrates of lung adenocarcinoma (LUAD).

METHODS

WDR76 expressions in LUAD tissues and normal tissues were primarily compared by The Cancer Genome Atlas (TCGA) database, and were validated in cohorts from Gene Expression Omnibus (GEO) database. The associations between WDR76 expression and clinicopathologic characteristics were analyzed. Kaplan-Meier and Cox regression analyses were performed to determine the impact of WDR76 expression on survival outcomes. The protein interaction network of WDR76 was built using STRING website. TIMER and GEPIA databases were used to investigate the correlation between WDR76 expression and immune infiltrates.

RESULTS

WDR76 expression was elevated in LUAD ( < 0.001) and high WDR76 expression was associated with advanced N stage, M stage and pathologic stage. Expectedly, high WDR76 expression significantly correlated with poor survival outcomes and was the independent risk factor for overall survival (OS) (HR 1.468, 95% CI [1.031-2.089],  = 0.033) and disease specific survival (DSS) (HR 1.764, 95% CI [1.095-2.842],  = 0.020). DDB1 and LSH were the important proteins interacting with WDR76. WDR76 expression correlated with CD8+ T cells presence and was also positively associated with levels of inhibitory receptors.

CONCLUSION

WDR76 expression was involved in the regulation of immune infiltrates and had predictive value for prognosis in LUAD.

摘要

背景

WD重复结构域76(WDR76)是WD40重复结构域超家族的一个预测成员,可能参与多种生物学过程,但其在癌症中的功能尚不清楚。本研究旨在评估WDR76在肺腺癌(LUAD)预后和免疫浸润中的作用。

方法

通过癌症基因组图谱(TCGA)数据库初步比较LUAD组织和正常组织中WDR76的表达,并在基因表达综合数据库(GEO)的队列中进行验证。分析WDR76表达与临床病理特征之间的关联。进行Kaplan-Meier和Cox回归分析,以确定WDR76表达对生存结果的影响。使用STRING网站构建WDR76的蛋白质相互作用网络。利用TIMER和GEPIA数据库研究WDR76表达与免疫浸润之间的相关性。

结果

LUAD中WDR76表达升高(<0.001),高WDR76表达与晚期N分期、M分期和病理分期相关。不出所料,高WDR76表达与较差的生存结果显著相关,是总生存(OS)(HR 1.468,95%CI[1.031-2.089],=0.033)和疾病特异性生存(DSS)(HR 1.764,95%CI[1.095-2.842],=0.020)的独立危险因素。DDB1和LSH是与WDR76相互作用的重要蛋白质。WDR76表达与CD8+T细胞的存在相关,也与抑制性受体水平呈正相关。

结论

WDR76表达参与免疫浸润的调节,对LUAD的预后具有预测价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/128c/8496460/849fc01c8183/peerj-09-12277-g001.jpg

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