Deciphering nasopharyngeal carcinoma pathogenesis via proteomics

ABSTRACT

Introduction: Nasopharyngeal carcinoma (NPC) is a distinct head and neck squamous cell carcinoma in its etiological association of Epstein–Barr virus (EBV) infection, hidden anatomical location, remarkable racial and geographical distribution, and high incidence of locoregional recurrence or metastasis. Thanks to the advancements in proteomics in recent decades, more understanding of the disease etiology, carcinogenesis, and progression has been gained, potentially deciphering the molecular characteristics of the malignancy.

Areas covered: In this review, we provide an overview of the proteomic aberrations that are likely involved or drive NPC development and progression, focusing on the contributions of major EBV-encoded factors, intercommunication with environment, protein features of high metastasis and therapy resistance, and protein–protein interactions that allow NPC cells to evade immune recognition and elimination. Finally, multistep carcinogenesis and subtypes of NPC from a proteomic perspective are inquired.

Expert commentary: Proteomic studies have covered various aspects involved in NPC pathogenesis, yet much remains to be uncovered. Coherent study designs, optimal conditions for obtaining high-quality data, and compelling interpretation are critical in ensuring the emergence of good science out of NPC proteomics. NPC proteogenomics and proteoform analysis are two promising fields to promote the application of the proteomic findings from bench to bedside.

KEYWORDS:

• Epstein–Barr virus
• secretome
• interactome
• metastasis
• multistep carcinogenesis
• nasopharyngeal carcinoma
• proteomics
• therapy resistance

Article highlights

• NPC is a proteomic disease, characterized by EBV infection, and a remarkable racial and geographical distribution.

• EBV and the encoded products are found participating in p53-mediated signaling pathway, NF-κB pathway, NPC angiogenesis, metastasis, and oxidative stress response pathway.

• Secreted proteome in NPC is distinctive from the normal control and plays characteristic roles in the tumor–host cross talk, modulating angiogenesis, immune response, cell proliferation, and tumor invasion.

• The proteomic characteristics associated with NPC metastasis are studied in various cell line models and microdissected tissues such as NPC stroma, revealing multiple metastasis-related biomarkers and alterations in protein phosphorylation and mitochondrial proteome.

• The mechanisms of radioresistance and chemoresistance in NPC and the protein biomarkers responsive to radiotherapy and chemotherapy are explored in proteomic studies.

• Protein interactome researches explain the molecular mechanisms for NPC cells to evade immune recognition and elimination.

• Differentiated expressed proteins of NPC histopathological subtypes and various TNM stages are identified to provide clues for understanding NPC carcinogenesis and early detection of NPC.

• In prospect, NPC proteogenomics and proteoforms might be the next research field, and the aspects including coherent study designs, optimal conditions for obtaining high-quality data, and compelling interpretation need to be improved.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was supported by National Natural Science Foundation of China [No.81202129], and Major State Basic Research Development Program of China 973 Program: No. [2014CBA02000-4].