Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer.
Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer.
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基质细胞相关M2巨噬细胞中PLXDC2的过表达与EMT和胃癌进展有关
DOI：
10.3389/fcell.2021.673295
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发表时间：
2021
影响因子：
5.5
通讯作者：
Hu Y
中科院分区：
文献类型：
--
作者：
Guan Y;Du Y;Wang G;Gou H;Xue Y;Xu J;Li E;Chan DW;Wu D;Xu P;Ni P;Xu D;Hu Y
肿瘤微环境（TME）由不同的细胞类型组成，包括成纤维细胞和巨噬细胞等基质类型，它们最近已成为肿瘤发生和进展的关键因素。在这里，我们在高基质分数群体中鉴定了 TME 相关基因，即含有 2 的 plexin 结构域 (PLXDC2)。我们从癌症基因组图谱数据库中发现，该基因与胃癌 (GC) 患者的较差生存率和晚期（肿瘤-淋巴结-转移）阶段有关。对肿瘤浸润免疫细胞比例的整合基因谱和功能分析表明，M2巨噬细胞标记物CD163的表达与PLXDC2表达呈正相关。此外，M2巨噬细胞基因特征和高PLXDC2表达与炎症信号通路和上皮间质转化（EMT）相关基因特征相关。 GC 的单细胞研究发现 PLXDC2 在成纤维细胞和单核细胞/巨噬细胞群中特异性富集，这支持了其在基质中的重要作用。此外，根据组织微阵列免疫组织化学分析，与肿瘤组织样本相比，人GC基质样本中PLXDC2的表达升高。此外，基质室中PLXDC2的过度表达与CD163阳性调节性M2巨噬细胞相关，其功能与GC的发病机制相关。多重免疫组织化学验证了 PLXDC2 与 EMT 标志物的相关性。我们的数据表明 PLXDC2 在基质细胞中表达，并且它与肿瘤相关巨噬细胞的串扰可以通过诱导 EMT 过程来促进癌症生物学。
The tumor microenvironment (TME) comprises distinct cell types, including stromal types such as fibroblast cells and macrophage cells, which have recently become a critical factor in tumor development and progression. Here, we identified the TME-related gene, plexin domain containing 2 (PLXDC2), in a high-stromal-score population. And we revealed that this gene was related to poor survival and advanced (tumor-node-metastasis) stage in gastric cancer (GC) patients from The Cancer Genome Atlas database. An integrated gene profile and functional analysis of the proportions of tumor-infiltrating immune cells revealed that the expression of the M2 macrophages cell marker CD163 was positively correlated with PLXDC2 expression. In addition, the M2 macrophages gene signature and high PLXDC2 expression were associated with the inflammatory signaling pathway and the epithelial-to-mesenchymal transition (EMT)-related gene signature. Single-cell study of GC identified PLXDC2 was enriched specifically in fibroblasts and monocytes/macrophages populations, which supported its important role in the stroma. Furthermore, according to a tissue microarray immunohistochemistry analysis, the expression of PLXDC2 elevated in human GC stromal specimens compared to tumor tissue specimens. Moreover, PLXDC2 overexpression in the stromal compartment was associated with CD163-positive regulatory M2 macrophages, and its functions were related to the pathogenesis of GC. Multiplexed immunohistochemistry verified PLXDC2’s correlation with EMT markers. Our data suggested that PLXDC2 was expressed in stromal cells and that its crosstalk with tumor-associated macrophages could contribute to cancer biology by inducing the EMT process.
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影响因子：
48
作者：
Huber W;Carey VJ;Gentleman R;Anders S;Carlson M;Carvalho BS;Bravo HC;Davis S;Gatto L;Girke T;Gottardo R;Hahne F;Hansen KD;Irizarry RA;Lawrence M;Love MI;MacDonald J;Obenchain V;Oleś AK;Pagès H;Reyes A;Shannon P;Smyth GK;Tenenbaum D;Waldron L;Morgan M
通讯作者：
Morgan M
DOI：
10.1073/pnas.1720948115
发表时间：
2018-04-24
影响因子：
11.1
作者：
Peranzoni E;Lemoine J;Vimeux L;Feuillet V;Barrin S;Kantari-Mimoun C;Bercovici N;Guérin M;Biton J;Ouakrim H;Régnier F;Lupo A;Alifano M;Damotte D;Donnadieu E
通讯作者：
Donnadieu E
影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
单细胞 RNA 测序强调了炎性癌症相关成纤维细胞在膀胱尿路上皮癌中的作用。
影响因子：
16.6
作者：
Chen Z;Zhou L;Liu L;Hou Y;Xiong M;Yang Y;Hu J;Chen K
通讯作者：
Chen K
锌指蛋白 CTCF 调节胃癌中与 Wnt 信号通路相关的细胞外基质 (ECM) 相关基因表达
影响因子：
4.7
作者：
Liu C;Deng L;Lin J;Zhang J;Huang S;Zhao J;Jin P;Xu P;Ni P;Xu D;Ying L;Hu Y
通讯作者：
Hu Y