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揭示人类胰腺癌中差异表达的标志物和异质性。

Uncovering Differently Expressed Markers and Heterogeneity on Human Pancreatic Cancer.

作者信息

Yoon Sorah, Li Haiqing, Quintanar Loren, Armstrong Brian, Rossi John J

机构信息

Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, California, 91010, USA.

Research Informatics, City of Hope, Duarte, California, 91010, USA.

出版信息

Transl Oncol. 2020 Mar;13(3):100749. doi: 10.1016/j.tranon.2020.100749. Epub 2020 Mar 3.

Abstract

Discovery of biomarkers is critical to understand tumor heterogeneity and microenvironment. To determine differently expressed makers on cancer tissue for comprehensive profiling, the multiplexed tissue imaging mass cytometer (IMC) which uniquely combines time-of-flight mass spectrometry with metal-labeling technology to enable breakthrough discovery on single cell level was employed to investigate the expression of seven markers related to the epithelial-to-mesenchymal transition [α-smooth muscle actin (α-SMA), vimentin, collagen I, cytokeratin 7, pan-keratin], tumor proliferation (Ki-67), and human leucocyte antigen (HLA-DR) on human pancreatic cancer tissue. The difference was analyzed using bioinformatic tools. We observed the high expression of α-SMA, vimentin, collagen I, and Ki-67 on grade I but not on grade III. HLA-DR was highly expressed on grade I/III but not on grade II. Overall, the expression of markers has elucidated the heterogeneity intratumors. Additionally, to identify biomarkers on pancreatic cancer cells by blind systematic evolution of ligands by exponential enrichment (SELEX), aptamer pull-down assay and liquid chromatography-tandem mass spectrometry were used. Mortalin was identified as a potential a prognostic marker of pancreatic cancer. Our studies demonstrate that the IMC and blind SELEX might be implemented to discover biomarkers which can be used to better understand tumor biology and biomedical research applications.

摘要

生物标志物的发现对于理解肿瘤异质性和微环境至关重要。为了确定癌症组织上差异表达的标志物以进行全面分析,采用了多重组织成像质谱仪(IMC),它将飞行时间质谱与金属标记技术独特地结合起来,能够在单细胞水平上实现突破性发现,以研究与上皮-间质转化相关的七种标志物[α-平滑肌肌动蛋白(α-SMA)、波形蛋白、胶原蛋白I、细胞角蛋白7、泛角蛋白]、肿瘤增殖(Ki-67)和人类白细胞抗原(HLA-DR)在人胰腺癌组织上的表达。使用生物信息学工具分析差异。我们观察到α-SMA、波形蛋白、胶原蛋白I和Ki-67在I级而非III级上高表达。HLA-DR在I/III级上高表达而在II级上不高表达。总体而言,标志物的表达阐明了肿瘤内的异质性。此外,为了通过指数富集的配体系统进化(SELEX)在胰腺癌细胞上鉴定生物标志物,使用了适体下拉分析和液相色谱-串联质谱。Mortalin被鉴定为胰腺癌的潜在预后标志物。我们的研究表明,IMC和盲法SELEX可能被用于发现可用于更好地理解肿瘤生物学和生物医学研究应用的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6504/7056725/f1afcbed123d/gr1.jpg

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