Neoplastic signatures: Comparative proteomics of canine hepatobiliary neuroendocrine tumors to normal niche tissue.
Neoplastic signatures: Comparative proteomics of canine hepatobiliary neuroendocrine tumors to normal niche tissue.
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DOI：
10.1371/journal.pone.0280928
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
Johnston, Andrea N.
中科院分区：
文献类型：
--
作者：
Batts, Tifini L.;Sasaki, Emi W.;Miller, Mayzie;Sparago, Joshua;Bauer, Rudy W.;Paulsen, Daniel D.;Boudreaux, Bonnie N.;Liu, Chin-Chi;Byrum, Stephanie D.;Johnston, Andrea N.
肝胆神经内分泌肿瘤在人类和狗中是罕见的癌症。到目前为止，在任何物种中都没有大规模的原发性肝胆肿瘤组学分析。这限制了诊断生物标志物和靶向治疗的发展。神经内分泌癌是一组异质性肿瘤，按其起源组织分类。由于神经内分泌肿瘤的解剖学生态位形成肿瘤表型，我们试图比较3只犬肝胆肿瘤与正常肝胆组织和肾上腺的蛋白质组，目的是识别独特的蛋白质特征。从福尔马林固定的石蜡包埋样品中提取蛋白质，并进行串联质谱分析。32个上调和126个下调的差异表达蛋白被鉴定。值得注意的是，6种（19%）上调的蛋白质与非肝胆神经内分泌肿瘤相关，16种（50%）在神经内分泌信号传导的关键外泌体细胞区室中进行了功能注释。26种（21%）下调的蛋白质在与癌症改变一致的代谢途径中富集。这些结果表明，特征性肿瘤蛋白质签名可以收集从小数据集使用比较蛋白质组学方法。
Hepatobiliary neuroendocrine neoplasms are rare cancers in humans and dogs. To date, no large-scale primary hepatobiliary neoplasm omics analyses exist in any species. This limits the development of diagnostic biomarkers and targeted therapeutics. Neuroendocrine cancers are a heterogenous group of neoplasms categorized by their tissue-of-origin. Because the anatomic niche of neuroendocrine neoplasms shapes tumor phenotype, we sought to compare the proteomes of 3 canine hepatobiliary neoplasms to normal hepatobiliary tissue and adrenal glands with the objective of identifying unique protein signatures. Protein was extracted from formalin-fixed paraffin-embedded samples and submitted for tandem mass spectroscopy. Thirty-two upregulated and 126 downregulated differentially expressed proteins were identified. Remarkably, 6 (19%) of the upregulated proteins are correlated to non-hepatobiliary neuroendocrine neoplasia and 16 (50%) are functionally annotated within the exosome cellular compartment key to neuroendocrine signaling. Twenty-six (21%) downregulated proteins are enriched in metabolic pathways consistent with alterations in cancer. These results suggests that characteristic neoplastic protein signatures can be gleaned from small data sets using a comparative proteomics approach.
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