Comparative RNA-Seq Analysis Revealed Tissue-Specific Splicing Variations during the Generation of the PDX Model.
Comparative RNA-Seq Analysis Revealed Tissue-Specific Splicing Variations during the Generation of the PDX Model.
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DOI：
10.3390/ijms242317001
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发表时间：
2023-11-30
影响因子：
5.6
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中科院分区：
文献类型：
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组织特异性基因表达在每个组织的功能中产生根本差异，并影响由此产生的肿瘤的特征。然而，目前还不清楚在将原发性肿瘤移植到免疫受损小鼠模型中的过程中有多少组织特异性是保守的。在这里，我们对四种不同的原发性患者来源的异种移植（PDX）肿瘤进行了比较RNA-seq分析。分析揭示了一个保守的RNA生物型分布的主要−PDX对，如先前的工作所揭示的。有趣的是，我们检测到PDX剪接模式的显著变化，其主要由跳过的外显子组成。这通过剪接变体特异性RT-PCR分析证实。另一方面，组织特异性基因的相关性分析表明，原发性和PDX肿瘤对之间总体上存在强正相关性，但胃癌病例除外，其显示出负相关性。这些数据表明，PDX形成过程中剪接事件的组织特异性变化是影响初级-PDX完整性的可变因素。
Tissue-specific gene expression generates fundamental differences in the function of each tissue and affects the characteristics of the tumors that are created as a result. However, it is unclear how much the tissue specificity is conserved during grafting of the primary tumor into an immune-compromised mouse model. Here, we performed a comparative RNA-seq analysis of four different primary-patient derived xenograft (PDX) tumors. The analysis revealed a conserved RNA biotype distribution of primary−PDX pairs, as revealed by previous works. Interestingly, we detected significant changes in the splicing pattern of PDX, which was mainly comprised of skipped exons. This was confirmed by splicing variant-specific RT-PCR analysis. On the other hand, the correlation analysis for the tissue-specific genes indicated overall strong positive correlations between the primary and PDX tumor pairs, with the exception of gastric cancer cases, which showed an inverse correlation. These data propose a tissue-specific change in splicing events during PDX formation as a variable factor that affects primary−PDX integrity.
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