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AFF3 是一种新型的预后生物标志物,也是胃癌免疫治疗的潜在靶点。

AFF3 is a novel prognostic biomarker and a potential target for immunotherapy in gastric cancer.

机构信息

Department of Blood Transfusion, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou City, China.

Department of Hepatobiliary Surgery, Zhengzhou Central Hospital Affiliated of Zhengzhou University, Zhengzhou City, China.

出版信息

J Clin Lab Anal. 2022 Jun;36(6):e24437. doi: 10.1002/jcla.24437. Epub 2022 Apr 27.

Abstract

BACKGROUND

Gastric cancer (GC) is one of the most common cancers worldwide with a poor prognosis. The tumor microenvironment (TME) serves a pivotal role in affecting the prognosis and efficacy of immunotherapy. Given the poor prognosis of GC patients and the limitation of immunotherapy, we urged to identify new prognostic and immunotherapeutic biomarkers.

METHODS

The transcriptome data were downloaded from the TCGA, GEO, and GEPIA databases, and performed differential analysis of AFF3 in tumor samples and normal samples. The UALCAN, Kaplan-Meier plotter and GEPIA databases were employed to assess the correlation of AFF3 with clinicopathological characteristics and prognosis. The potential mechanism of AFF3 was explored by the GO and KEGG enrichment. The potential role of AFF3 on tumor-infiltrating immune cells (TIICs) was explored by TIMER2.0 and TISIDB. TIMER2.0 and SangerBox3.0 databases were, respectively, used to determine the correlation of AFF3 with immune checkpoint (ICs), tumor mutational burden (TMB), and microsatellite instability (MSI) in GC.

RESULTS

We found significant downregulation of AFF3 in GC tissues as compared with normal tissues. However, GC patients having a higher expression of AFF3 were found to have worse clinicopathological characteristics and prognosis. Moreover, the GO enrichment analysis illustrated that AFF3 might regulate the immune cells in the TME. In addition, the AFF3 was positively correlated with TIICs, ICs, TMB, and MSI.

CONCLUSION

Here, we conclude that AFF3 may be a promising potential marker for the diagnosis and prognosis of GC patients, and may influence response to ICIs by affecting TIICs and ICs expression in the TME.

摘要

背景

胃癌(GC)是全球最常见的癌症之一,预后较差。肿瘤微环境(TME)在影响免疫治疗的预后和疗效方面起着关键作用。鉴于 GC 患者的预后较差和免疫治疗的局限性,我们迫切需要确定新的预后和免疫治疗生物标志物。

方法

从 TCGA、GEO 和 GEPIA 数据库下载转录组数据,并对肿瘤样本和正常样本中的 AFF3 进行差异分析。使用 UALCAN、Kaplan-Meier plotter 和 GEPIA 数据库评估 AFF3 与临床病理特征和预后的相关性。通过 GO 和 KEGG 富集探索 AFF3 的潜在机制。通过 TIMER2.0 和 TISIDB 探索 AFF3 对肿瘤浸润免疫细胞(TIICs)的潜在作用。分别使用 TIMER2.0 和 SangerBox3.0 数据库确定 AFF3 与 GC 中的免疫检查点(ICs)、肿瘤突变负担(TMB)和微卫星不稳定性(MSI)的相关性。

结果

我们发现 AFF3 在 GC 组织中的表达明显低于正常组织。然而,AFF3 表达较高的 GC 患者具有更差的临床病理特征和预后。此外,GO 富集分析表明,AFF3 可能调节 TME 中的免疫细胞。此外,AFF3 与 TIICs、ICs、TMB 和 MSI 呈正相关。

结论

我们得出结论,AFF3 可能是 GC 患者诊断和预后的有前途的潜在标志物,通过影响 TME 中的 TIICs 和 ICs 表达,可能影响对 ICIs 的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b4f/9169183/4b559998b6ba/JCLA-36-e24437-g004.jpg

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