OSCAR facilitates malignancy with enhanced metastasis correlating to inhibitory immune microenvironment in multiple cancer types.
OSCAR facilitates malignancy with enhanced metastasis correlating to inhibitory immune microenvironment in multiple cancer types.
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DOI：
10.7150/jca.51964
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发表时间：
2021
影响因子：
3.9
通讯作者：
Zhang C
中科院分区：
文献类型：
--
作者：
Liao X;Bu Y;Zhang Y;Xu B;Liang J;Jia Q;Zhang C
肿瘤和免疫微环境之间的相互作用在恶性进展中发挥着关键作用。破骨细胞相关受体 (OSCAR) 是淋巴细胞分化和成熟的调节因子，但人们对 OSCAR 在多种癌症类型中的作用知之甚少。我们使用 Oncomine、TIMER、Gene GEPIA2 和 CCLE 综合分析了 OSCAR 表达，并探讨了其与多种癌症类型预后的相关性。我们使用 UALCAN 和 GEPIA2 检查了肿瘤样本中 OSCAR 表达与淋巴结转移和病理分期的相关性。我们使用 Kaplan Meier 绘图仪分析了 OSCAR 对生存的影响。我们使用 LinkedOmics 数据库探索与 OSCAR 共表达的基因，并使用 Metascape 分析相关基因本体。此外，我们使用 TIMER 检查了 OSCAR 表达与免疫细胞浸润、上皮间质转化标志物和淋巴细胞亚型之间的相关性。与邻近正常组织相比，大多数癌症类型中 OSCAR mRNA 水平上调。 OSCAR 的较高表达与淋巴结转移或晚期亚组相关。 OSCAR 的高表达与肿瘤纯度低有关，大多数癌症类型中 M2 巨噬细胞极化、T 细胞耗竭和间充质表型水平增加。我们还表明，自然杀伤细胞的浸润减轻了 OSCAR 表达对恶性进展和抑制性免疫微环境的影响强度。这些发现揭示了 OSCAR 在大多数癌症类型中的促癌作用，并表明 OSCAR 可以成为未来疗法的目标，以逆转抑制性免疫微环境。
Cross talk between tumors and the immune microenvironment play a critical role in the malignant progression. The osteoclast-associated receptor (OSCAR) is a regulator of lymphocyte differentiation and maturation, but little is known about the role of OSCAR in multiple cancer types. We comprehensively analyzed OSCAR expression and explored its correlation with prognosis in multiple cancer types using Oncomine, TIMER, Gene GEPIA2 and CCLE. We examined OSCAR expression correlations with lymph node metastasis and pathological stage across tumor samples using UALCAN and GEPIA2. We analyzed the effects of OSCAR on survival using the Kaplan Meier plotter. We explored genes co-expressed with OSCAR using the LinkedOmics database and analyzed associated gene ontologies using Metascape. Further, we examined the correlation between OSCAR expression and immunocyte infiltration, markers of epithelial-mesenchymal transition, and lymphocyte subtypes using TIMER. OSCAR mRNA levels were upregulated in most cancer types compared with adjacent normal tissues. Higher expression of OSCAR correlated with lymph node metastasis or advanced stage subgroups. High expression of OSCAR was related to low tumor purity, with increased levels of M2 macrophage polarization, T cells exhaustion, and mesenchymal phenotype in most cancer types. We also showed that the strength of OSCAR expression influence in malignant progression and inhibitory immune microenvironment is mitigated by the infiltration of natural killer cells. These findings shed light on the pro-carcinogenic role of OSCAR in most cancer types and indicate OSCAR could be targeted in future therapeutics to reverse the inhibitory immune microenvironment.
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影响因子：
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