Transcriptomic analysis identifies a tumor subtype mRNA classifier for invasive non-functioning pituitary neuroendocrine tumor diagnostics.
Transcriptomic analysis identifies a tumor subtype mRNA classifier for invasive non-functioning pituitary neuroendocrine tumor diagnostics.
复制标题
转录组分析确定了肿瘤亚型mRNA分类剂，用于侵入性无功能的垂体神经内分泌肿瘤诊断。
作者：
Bao X;Wang G;Yu S;Sun J;He L;Zhao H;Ma Y;Wang F;Wang X;Wang R;Yu J
理由：无功能垂体神经内分泌肿瘤（NF-PitNEts）的侵袭性行为给完全手术切除带来了障碍，预示着预后不良。因此，开发可靠的诊断工具来识别侵袭性PitNEts将有助于指导手术决策，特别是后续治疗。方法：通过高通量测序、基因共表达和功能注释分析了39例非侵袭性和22例侵袭性NF-PitNEts的差异基因表达谱。在另外143份NF-PitNEt样本中，用Taqman-qPCR进一步验证了21个转录本。采用组织芯片和微滴数字PCR检测3个候选基因的组织学表达和血清外泌体mRNA。结果：非侵入性和侵入性NF-PitNEts由于其促性腺激素、促皮质激素或无细胞谱系而聚集成不同的组，并有一些异常值。具有强侵袭潜力的基因标记在“癌症通路”和“MAPK通路”中富集，在侵袭性NF-PitNEts中INSM1和HSPA2蛋白的原位表达显著升高。进一步整合20个qpcr验证的差异表达基因和垂体细胞系，提供了一个基因亚型面板，对NF-PitNEts的侵袭性诊断准确率为80.00-90.24%。结论：我们的方法定义了有侵袭性NF-PitNEt风险患者核心分子网络的新特征，代表了侵袭性PitNEt诊断的重大临床进展。
Rationale: The invasive behavior of non-functioning pituitary neuroendocrine tumors (NF-PitNEts) presents obstacles for complete surgical resection and is indicative of poor prognosis. Therefore, developing reliable diagnostic tools for identifying invasive PitNEts would be helpful in guiding surgical decisions and, in particular, the follow-up treatment. Methods: We analyzed differential gene expression profiles between 39 non-invasive and 22 invasive NF-PitNEts by high-throughput sequencing, gene co-expression, and functional annotation. Twenty-one transcripts were further validated by Taqman-qPCR in another 143 NF-PitNEt samples. The histological expression and serum-exosomal mRNA of three candidate genes were examined by tissue microarray and droplet digital PCR. Results: Non-invasive and invasive NF-PitNEts were clustered into distinct groups with a few outliers because of their gonadotroph, corticotroph, or null cell lineages. The gene signature with strong invasive potential was enriched in 'Pathways in cancers' and 'MAPK pathway', with significantly higher in situ INSM1 and HSPA2 protein expression in invasive NF-PitNEts. Further integration of the 20 qPCR-validated differentially expressed genes and pituitary cell lineages provided a gene-subtype panel that performed 80.00-90.24% diagnostic accuracy for the invasiveness of NF-PitNEts. Conclusion: Our approach defined new characteristics in the core molecular network for patients at risk for invasive NF-PitNEt, representing a significant clinical advance in invasive PitNEt diagnostics.
影响因子：
3.9
作者：
Wallace TJ;Qian J;Avital I;Bay C;Man YG;Wellman LL;Moskaluk C;Troyer D;Ramnani D;Stojadinovic A
通讯作者：
Stojadinovic A