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hsa-miR-9-5p 介导的 TSPAN9 下调与肝细胞癌不良预后和肿瘤免疫浸润呈正相关。

hsa-miR-9-5p-Mediated TSPAN9 Downregulation Is Positively Related to Both Poor Hepatocellular Carcinoma Prognosis and the Tumor Immune Infiltration.

机构信息

Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, 410078 Hunan, China.

Department of Epidemiology and Health Statistics, Guilin Medical University, Guilin, 541004 Guangxi, China.

出版信息

J Immunol Res. 2022 May 12;2022:9051229. doi: 10.1155/2022/9051229. eCollection 2022.

Abstract

Tetraspanins (TSPANs) play crucial roles in cell adhesion, migration, and metastasis of human cancer. However, there is no study in revealing the aspects of TSPAN9 traits and its functions in hepatocellular carcinoma (HCC) prognosis. Our study is the first to portray the TSPAN9 expression in HCC tissues with immunohistochemistry (IHC) analysis. Subsequently, a series of bioinformatics analyses such as expression estimation, survival assessment, and correlation analysis were implemented to dig out the possible upstream noncoding RNAs (ncRNAs) for TSPAN9 in HCC. In this way, the relevance within TSPAN9 and tumor immunity was then explored. We found that the TSPAN9 was downregulated in HCC tissues and had a correlation with HCC prognosis. Furthermore, we identified that the AL139383.1-hsa-miR-9-5p axis was the upstream ncRNA-related pathway most associated with TSPAN9 in HCC. Besides that, expression of TSPAN9 held a significantly negative correlation with tumor immunocyte infiltration as well as immune checkpoint CTLA4. TSPAN9-related immunomodulators were mainly enriched in T cell activation, leukocyte cell-cell adhesion, regulation of T cell activation, and regulation of leukocyte cell-cell adhesion signaling pathway. In conclusion, our results indicated that hsa-miR-9-5p-mediated downregulation of TSPAN9 was associated with poor HCC prognosis, immune-related signaling pathway, and tumor immune infiltration.

摘要

四跨膜蛋白(Tetraspanins,TSPANs)在人类癌症的细胞黏附、迁移和转移中发挥着关键作用。然而,目前尚无研究揭示 TSPAN9 特征及其在肝细胞癌(HCC)预后中的功能。我们的研究首次通过免疫组织化学(IHC)分析描绘了 HCC 组织中 TSPAN9 的表达。随后,我们进行了一系列生物信息学分析,如表达估计、生存评估和相关性分析,以挖掘 HCC 中 TSPAN9 的可能上游非编码 RNA(ncRNA)。通过这种方式,我们进一步探讨了 TSPAN9 与肿瘤免疫之间的相关性。我们发现 TSPAN9 在 HCC 组织中下调,并且与 HCC 预后相关。此外,我们确定了 AL139383.1-hsa-miR-9-5p 轴是与 HCC 中 TSPAN9 最相关的上游 ncRNA 相关途径。此外,TSPAN9 的表达与肿瘤免疫细胞浸润以及免疫检查点 CTLA4 呈显著负相关。TSPAN9 相关免疫调节剂主要富集在 T 细胞激活、白细胞细胞间黏附、T 细胞激活调节以及白细胞细胞间黏附信号通路调节中。总之,我们的研究结果表明,hsa-miR-9-5p 介导的 TSPAN9 下调与 HCC 不良预后、免疫相关信号通路和肿瘤免疫浸润有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f247/9119760/ccae0bcaee07/JIR2022-9051229.001.jpg

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