PURPOSE In hopes of discovering new markers for metastatic or aggressive phenotypes of pheochromocytomas and paragangliomas (PCPG), we analyzed the noncoding transcriptome from patient gene expression data in The Cancer Genome Atlas. METHODS Differential expression of miRNAs was observed between PCPG molecular subtypes. We specifically characterized candidate miRNAs that are upregulated in pseudohypoxic PCPGs with mutations in succinate dehydrogenase complex subunits, B and/or D (SDHB and/or SDHD, respectively), which are mutations associated with unfavorable clinical outcomes. RESULTS Our computational analysis identified four candidate miRNAs that showed elevated expression in metastatic compared to non-metastatic PCPGs: miR-182, miR-183, miR-96, and miR-383. We also found six candidate lncRNAs harboring opposite expression patterns from the miRNAs when we analyzed the expression profiles of their predicted target lncRNAs. Three of these lncRNA candidates, USP3-AS1, LINC00877, and AC009312.1, were validated to have reduced expression in metastatic compared to non-metastatic PCPGs. Finally, using univariate and multivariate analysis, we found miRNA miR-182 to be an independent predictor of metastasis-free survival in PCPGs. CONCLUSIONS We identified candidate miRNA and lncRNAs associated with metastasis-free survival in PCPGs.

中文翻译：

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长非编码 RNA-microRNA 表达特征可预测嗜铬细胞瘤和副神经节瘤的转移特征。

目的为了发现嗜铬细胞瘤和副神经节瘤（PCPG）转移性或侵袭性表型的新标记，我们分析了癌症基因组图谱中患者基因表达数据的非编码转录组。方法观察 PCPG 分子亚型之间 miRNA 的差异表达。我们特别鉴定了在假性缺氧 PCPG 中上调的候选 miRNA，其琥珀酸脱氢酶复合体亚基 B 和/或 D（分别为 SDHB 和/或 SDHD）发生突变，这些突变与不利的临床结果相关。结果我们的计算分析确定了四种候选 miRNA，与非转移性 PCPG 相比，它们在转移性 PCPG 中表达升高：miR-182、miR-183、miR-96 和 miR-383。当我们分析预测的目标 lncRNA 的表达谱时，我们还发现了 6 个候选 lncRNA，它们的表达模式与 miRNA 相反。其中三种 lncRNA 候选物 USP3-AS1、LINC00877 和 AC009312.1 经验证，与非转移性 PCPG 相比，转移性 PCPG 中的表达降低。最后，通过单变量和多变量分析，我们发现 miRNA miR-182 是 PCPG 中无转移生存的独立预测因子。结论 我们确定了与 PCPG 中无转移生存相关的候选 miRNA 和 lncRNA。通过单变量和多变量分析，我们发现 miRNA miR-182 是 PCPG 中无转移生存的独立预测因子。结论 我们确定了与 PCPG 中无转移生存相关的候选 miRNA 和 lncRNA。通过单变量和多变量分析，我们发现 miRNA miR-182 是 PCPG 中无转移生存的独立预测因子。结论 我们确定了与 PCPG 中无转移生存相关的候选 miRNA 和 lncRNA。