Mining Transcriptomic Data to Uncover the Association between CBX Family Members and Cancer Stemness.
Mining Transcriptomic Data to Uncover the Association between CBX Family Members and Cancer Stemness.
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DOI：
10.3390/ijms232113083
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发表时间：
2022-10-28
影响因子：
5.6
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中科院分区：
文献类型：
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遗传和表观遗传改变可能促进肿瘤干细胞样表型的获得，导致更糟糕的患者预后。尽管染色盒(CBX)结构域蛋白在几种肿瘤类型的发病机制中的作用已有很好的文献报道，但对它们与癌症干性的关系却知之甚少。在这里，我们利用公开可用的TCGA和GEO数据库，并利用几种生物信息学工具(即Oncomine、GEPIA2、TISIDB、GSCA、UALCAN、R2 Platform、Enrichr、GSEA)，表征了CBX家族成员的表达与肝、肺、胰腺和子宫肿瘤的癌症干性之间的关系。我们证明，CBX3的显著上调和CBX7的下调与不同肿瘤类型中丰富的肿瘤干细胞样表型一致相关。在表现出干细胞样特征的高级别肿瘤中观察到CBX3的高表达，无论肿瘤类型如何，CBX3相关的基因表达谱都被茎干标记和c-Myc转录因子靶标强健地丰富。与高干肿瘤类似，CBX3过表达的癌症表现出更高的突变负荷。另一方面，高级别肿瘤的特征是CBX7显著下调，CBX7相关基因表达谱明显被干细胞标记物耗尽。与高干肿瘤相比，CBX7上调的癌症表现出较低的突变负担。我们的结果清楚地表明，CBX3的高表达和CBX7的低表达与实体瘤的肿瘤干细胞样表型之间存在尚未被认识的关联。
Genetic and epigenetic changes might facilitate the acquisition of stem cell-like phenotypes of tumors, resulting in worse patients outcome. Although the role of chromobox (CBX) domain proteins, a family of epigenetic factors that recognize specific histone marks, in the pathogenesis of several tumor types is well documented, little is known about their association with cancer stemness. Here, we have characterized the relationship between the CBX family members’ expression and cancer stemness in liver, lung, pancreatic, and uterine tumors using publicly available TCGA and GEO databases and harnessing several bioinformatic tools (i.e., Oncomine, GEPIA2, TISIDB, GSCA, UALCAN, R2 platform, Enrichr, GSEA). We demonstrated that significant upregulation of CBX3 and downregulation of CBX7 are consistently associated with enriched cancer stem-cell-like phenotype across distinct tumor types. High CBX3 expression is observed in higher-grade tumors that exhibit stem cell-like traits, and CBX3-associated gene expression profiles are robustly enriched with stemness markers and targets for c-Myc transcription factor regardless of the tumor type. Similar to high-stemness tumors, CBX3-overexpressing cancers manifest a higher mutation load. On the other hand, higher-grade tumors are characterized by the significant downregulation of CBX7, and CBX7-associated gene expression profiles are significantly depleted with stem cell markers. In contrast to high-stemness tumors, cancer with CBX7 upregulation exhibit a lower mutation burden. Our results clearly demonstrate yet unrecognized association of high CBX3 and low CBX7 expression with cancer stem cell-like phenotype of solid tumors.
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影响因子：
--
作者：
Czerwińska P;Shah PK;Tomczak K;Klimczak M;Mazurek S;Sozańska B;Biecek P;Korski K;Filas V;Mackiewicz A;Andersen JN;Wiznerowicz M
通讯作者：
Wiznerowicz M
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
4.8
作者：
Kim, Hey-Yon;Park, Ji-Hye;Kong, Gu
通讯作者：
Kong, Gu
影响因子：
4.7
作者：
Carvalho, Joao
通讯作者：
Carvalho, Joao