Comprehensive analysis of BTN3A1 in cancers: mining of omics data and validation in patient samples and cellular models,FEBS Open Bio

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Comprehensive analysis of BTN3A1 in cancers: mining of omics data and validation in patient samples and cellular models
FEBS Open Bio ( IF 2.8 ) Pub Date : 2021-07-22 , DOI: 10.1002/2211-5463.13256
Fan Liang _{1,

2} , Chen Zhang _{1,

2} , Hua Guo ₂ , San-Hui Gao _{1,

2} , Fu-Ying Yang _{1,

2} , Guang-Biao Zhou ₂ , Gui-Zhen Wang ₂

Affiliation

Butyrophilin 3A1 (BTN3A1), a major histocompatibility complex-associated gene that encodes a membrane protein with two extracellular immunoglobulin domains and an intracellular B30.2 domain, is critical in T-cell activation and adaptive immune response. Here, the expression of BTN3A1 in cancers was analyzed in eight databases comprising 86 733 patients of 33 cancers, and the findings were validated in patient samples and cell models. We showed that BTN3A1 was expressed in most cancers, and its expression level was strongly correlated with clinical outcome of 13 cancers. Mutations of BTN3A1 were detected, and the mutations were distributed throughout the entire gene. Gene set enrichment analysis showed that BTN3A1 co-expression genes and interacting proteins were enriched in immune regulation-related pathways. BTN3A1 was associated with tumor-infiltrating immune cells and was co-expressed with multiple immune checkpoints in patients with breast cancer (BRCA) and non-small cell lung cancer (NSCLC). We reported that BTN3A1 was downregulated in 46 of 65 (70.8%) NSCLCs, and its expression level was inversely associated with clinical outcome of the patients. BTN3A1 in tumor samples was lower than in counterpart normal tissues in 31 of 38 (81.6%) BRCAs. Bioinformatics analyses showed that BTN3A1 could be a target gene of transcription factor Spi-1 proto-oncogene (SPI1), and our ‘wet’ experiments showed that ectopic expression of SPI1 upregulated, whereas silencing of SPI1 downregulated, BTN3A1 expression in cells. These results suggest that BTN3A1 may function as a tumor suppressor and may serve as a potential prognostic biomarker in NSCLCs and BRCAs.

中文翻译：

BTN3A1在癌症中的综合分析：组学数据的挖掘和患者样本和细胞模型的验证

Butyrophilin 3A1 ( BTN3A1 ) 是一种主要的组织相容性复合物相关基因，它编码具有两个细胞外免疫球蛋白结构域和一个细胞内 B30.2 结构域的膜蛋白，在 T 细胞活化和适应性免疫反应中至关重要。在这里，BTN3A1在癌症中的表达在 8 个数据库中进行了分析，这些数据库包括 33 种癌症的 86 733 名患者，并在患者样本和细胞模型中验证了研究结果。我们发现BTN3A1在大多数癌症中都有表达，其表达水平与 13 种癌症的临床结果密切相关。检测到BTN3A1的突变，突变分布在整个基因中。基因集富集分析表明，BTN3A1共表达基因和相互作用蛋白在免疫调节相关通路中富集。BTN3A1 与肿瘤浸润性免疫细胞相关，并与乳腺癌 (BRCA) 和非小细胞肺癌 (NSCLC) 患者的多个免疫检查点共同表达。我们报道 BTN3A1 在 65 例（70.8%）非小细胞肺癌中的 46 例中下调，其表达水平与患者的临床结果呈负相关。在 38 个 (81.6%) BRCA 中，肿瘤样本中的 BTN3A1 低于对应的正常组织中的 31 个。生物信息学分析表明BTN3A1可能是转录因子 Spi-1 原癌基因 (SPI1) 的靶基因，我们的“湿”实验表明 SPI1 的异位表达上调，而 SPI1 的沉默下调 BTN3A1 在细胞中的表达。这些结果表明，BTN3A1 可能作为肿瘤抑制因子发挥作用，并可能作为 NSCLC 和 BRCA 的潜在预后生物标志物。

更新日期：2021-09-01

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