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

Mengyan Zhu,Zhao Li,Yong Li,Jiaqi Wang,Cheng Ding,Ping Wang,Xiaoyan Zhang,Yangyang Ma,Nobuo Kanazawa

doi:10.1155/2020/9237381

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.

Highlights

Cutaneous T-cell lymphomas (CTCLs) originate from malignant T-lymphocytes, and their most common form is mycosis fungoides (MF), accounting for about 55% of cases [1]
The proteins IP-10, SOD2, S100A8, FABP5, and PARP-1 have been identified as potential biomarkers for MF in previous studies [7,8,9, 13]
CD26 soluble serum levels and the expression of TOX, Tplastin, TWIST, CD158, and nkP46 may contribute to the differential diagnosis of MF [18,19,20,21,22]

Summary

Introduction

Cutaneous T-cell lymphomas (CTCLs) originate from malignant T-lymphocytes, and their most common form is mycosis fungoides (MF), accounting for about 55% of cases [1]. MF can be classified into three stages: patch, plaque, and tumor. Most of the cases show indolent biologic behavior. Once there is a progressive skin lesion such as tumor, this disease will show significantly invasive biological behavior, including metastasis through peripheral blood, lymph nodes, or internal organs [2]. The early diagnosis and targeted therapy of MF are of real necessity. It is a great challenge to distinguish MF in the early stage from benign inflammatory skin diseases. Multifactors as BioMed Research International heredity and environment play an essential role in the occurrence and development of MF, but the etiology and pathogenesis of MF have not been elucidated [3]

Methods

Results

Conclusion