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ABSTRACT
Introduction
Proteins are molecules that have role in the progression of the diseases. Proteomics is a tool that can play an effective role in identifying diagnostic and therapeutic biomarkers for lung cancer. Cytokines are proteins that play a decisive role in activating body's immune system in lung cancer. They can increase the growth of the tumor (oncogenic cytokines) or limit tumor growth (anti-tumor cytokines) by regulating related signaling pathways such as proliferation, growth, metastasis, and apoptosis.
Areas covered
In the present study, a total of 223 papers including 196 research papers and 27 review papers, extracted from PubMed and Scopus and published from 1997 to present, are reviewed. The most important involved-cytokines in lung cancer including TNF-α, IFN- γ, TGF-β, VEGF and interleukins such as IL-6, IL-17, IL-8, IL-10, IL-22, IL-1β and IL-18 are introduced. Also, the pathological and biological role of such cytokines in cancer signaling pathways is explained.
Expert opinion
In lung cancer, the cytokine expression changes under the physiological conditions of the immune system, and inflammatory cytokines are associated with the progression of lung cancer. Therefore, the cytokine expression profile can be used in the diagnosis, prognosis, prediction of therapeutic responses, and survival of patients with lung cancer.
Article highlights
In this review paper cytokine proteomics studies in lung cancer and the biological and pathological roles of cytokines are reviewed.
Cytokines are proteins that play a key role in activating the body’s immune system in lung cancer and can be divided into two groups: oncogenic cytokines and anti-tumor cytokines.
Cytokines produced by inflammatory cells control numerous pro-tumorigenic processes and are involved in two stages of tumor initiation and tumor promotion.
Inflammatory cytokines that have been identified as potential targets for lung cancer include TNF-α, IFN-γ, TGF-β, VEGF and several interleukins such as IL-6, IL-17, IL-8, IL-10, IL-22, IL-1β and IL-18.
In lung cancer, the expression level of cytokine changes under the physiological conditions of the immune system.
The essential role of cytokines in the signaling pathways of lung cancer shows that some of them can be used as a diagnostic and prognostic biomarker.
Abbreviations
| Abbreviation | = | Meaning |
| SCLC | = | small cell lung cancer |
| NSCLC | = | non-small cell lung cancer |
| Ab | = | Antibody |
| 2D-PAGE | = | Two-Dimensional Gel Electrophoresis |
| SILAC | = | Stable Isotope Labeling by Amino acids in Cell culture |
| ICAT | = | ICAT: Isotope coded affinity tags |
| iTRAQ | = | Isobaric tags for relative and absolute quantitation |
| MS | = | Mass Spectrometry |
| ESI | = | Electrospray ionization |
| MALDI | = | Matrix-Assisted Laser Desorption Ionization |
| SELDI | = | Surface-Enhanced Laser Desorption/Ionization |
| TIF | = | Tissue Interstitial Fluid |
| FFPE | = | Formalin-Fixed Paraffin-Embedded |
| TNF-α | = | Tumor Necrosis Factor-α |
| IFN-γ | = | Interferon Gamma |
| TGF-β | = | Transforming Growth Factor Beta |
| VEGF | = | Vascular Endothelial Growth Factor |
| HIF | = | Hypoxia-Inducible Factor |
| EGR-1 | = | Early Growth Response-1 |
| EGFR | = | Epidermal Growth Factor |
| STAT | = | Signal Transducer and Activator of Transcription |
| KRAS | = | Kirsten rat sarcoma 2 viral oncogene homolog |
| SP-1 | = | Specificity Protein 1 |
| EMT | = | Epithelial-mesenchymal transition |
| TGFβR1 | = | TGF beta receptor 1 |
| SMAD | = | Sterile Alpha Motif Domain Containing |
| TRAF6 | = | TNF Receptor Associated Factor 6 |
| TAK1 | = | Transforming growth factor beta-activated kinase 1 |
| JNK | = | Jun N-terminal kinases |
| PI3K | = | Phosphoinositide 3-kinases |
| RhoA | = | Ras homolog family member A |
| ERK | = | Extracellular regulated kinases |
| AP-1 | = | Activator protein 1 |
| CTL | = | Cytotoxic T Lymphocytes |
| SOCS | = | Suppressor of Cytokine Signaling |
| MAPK | = | Mitogen-Activated Protein Kinase |
| NF-kB | = | Nuclear Factor-Kappa |
| JAK | = | Janus Kinase |
| PGE2 | = | Prostaglandin E2 |
| ROS | = | Reactive Oxygen Species |
| RNI | = | Reactive Nitrogen Intermediates |
| DEGs | = | Differentially Expressed Genes |
| CSCs | = | Cancer Stem Cells |
| PE | = | Pleural Effusion |
| BALF | = | Bronchoalveolar lavage fluid |
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 in this manuscript have no relevant financial or other relationships to disclose.