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采用相对和绝对定量同位素标记(isobaric tags for relative and absolute quantification,iTRAQ)技术的早期蕈样肉芽肿(mycosis fungoides,MF)的蛋白质组学特征分析及其意义

Proteomic Profiling Change and Its Implies in the Early Mycosis Fungoides (MF) Using Isobaric Tags for Relative and Absolute Quantification (iTRAQ).

机构信息

The Third People's Hospital of Hangzhou Affiliated to Zhejiang Chinese Medical University, Hangzhou 310009, China.

The Third People's Hospital of Hangzhou, Hangzhou 310009, China.

出版信息

Biomed Res Int. 2020 Nov 23;2020:9237381. doi: 10.1155/2020/9237381. eCollection 2020.

Abstract

PURPOSE

Mycosis fungoides (MF) is the most common T-cell lymphoma, with indolent biologic behavior in the early stage and features of invasive in the tumor stage. The diagnosis of MF is still ambiguous and difficult. We focused on the proteomic profiling change in the pathogenesis of early MF and identified candidate biomarkers for early diagnosis.

METHODS

We collected peripheral blood samples of MF patients and healthy individuals (HI) performed proteomic profiling analysis using isobaric tags for relative and absolute quantification (iTRAQ) platform. Differently expressed proteins (DEPs) were filtered, and involved biological functions were analyzed through Gene Ontology (GO) and Ingenuity Pathway Analysis (IPA) software.

RESULTS

We identified 78 DEPs including fifty proteins were upregulated and 28 proteins were downregulated in the MF group with HI as a control. Total DEPs were analyzed according to the biological regulation and metabolic process through GO analysis. The pathways of LXR/RXR activation and FXR/RXR activation were significantly activated, in which APOH, CLU, and ITIH4 were involved. The top annotated disease and function network was (Cancer, Organismal Injury and Abnormalities, Reproductive System Disease), with a key node CLU. These DEPs were involved in cancer, including thyroid carcinoma, head and neck carcinoma, and cancer of secretory structure, in which CLU, GNAS, and PKM played an indirect role in the occurrence and development of cancer. Relevant causal network was IL12 (family), which is related to GNAS, PKM, and other DEPs.

CONCLUSION

Proteomic profiling of early-stage MF provided candidate protein biomarkers such as CLU, GNAS, and PKM, which benefit the early diagnosis and understanding of the mechanism of MF development. Besides, lipid metabolism may be one of the pathogenesis of MF, and IL12 was a potential marker for the diagnosis and treatment of early MF.

摘要

目的

蕈样真菌病(MF)是最常见的 T 细胞淋巴瘤,在早期具有惰性的生物学行为,在肿瘤期则具有侵袭性。MF 的诊断仍然存在模糊和困难。我们专注于早期 MF 发病机制中的蛋白质组谱变化,并确定早期诊断的候选生物标志物。

方法

我们收集 MF 患者和健康个体(HI)的外周血样本,使用同位素相对标记与绝对定量(iTRAQ)平台进行蛋白质组谱分析。过滤差异表达蛋白(DEPs),并通过基因本体论(GO)和 IPA 软件分析涉及的生物学功能。

结果

我们鉴定了 78 个 DEPs,其中 50 个蛋白上调,28 个蛋白下调。根据 GO 分析,对总 DEPs 进行了生物调节和代谢过程的分析。LXR/RXR 激活和 FXR/RXR 激活途径明显激活,其中 APOH、CLU 和 ITIH4 参与其中。注释疾病和功能网络的顶级节点是 CLU,主要节点是 CLU。这些 DEPs 参与了癌症,包括甲状腺癌、头颈部癌和分泌结构癌,其中 CLU、GNAS 和 PKM 在癌症的发生和发展中起着间接作用。相关因果网络是 IL12(家族),与 GNAS、PKM 等 DEPs 相关。

结论

早期 MF 的蛋白质组谱分析提供了 CLU、GNAS 和 PKM 等候选蛋白生物标志物,有助于早期诊断和了解 MF 发病机制。此外,脂质代谢可能是 MF 发病机制之一,IL12 是早期 MF 诊断和治疗的潜在标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d43a/7707953/352a9cdf1af3/BMRI2020-9237381.001.jpg

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