Table 2 Potential protein biomarkers of head and neck cancers: Serum/plasma/saliva/secretome
From: A systematic review of proteomic biomarkers in oral squamous cell cancer
Sample | Technique | Biomarker [Accession no.] | Confirmation by | Biomarker for | Discussion | Reference |
|---|---|---|---|---|---|---|
OSCC | sDIGE&iTRAQ/2DLC | EGFR [A8K2T7] | ELISA; WB; IHC | Carcinogenesis | High EGFR expression is observed in OSCC suggesting that an uncontrolled growth may be mediated by abnormal EGFR expression. | |
OSCC | 2D-DIGE; MALDI-TOF MS | Vitamin D-binding protein [P02774] | ELISA; WB | OSCC plasma marker | Transport protein for Vitamin D sterols in serum that prevents polymerization of actin. The level of Vitamin D-binding protein level was significantly low in OSCC plasma. | |
OSCC plasma saliva | 2D-DIGE; MALDI-TOF MS | Fibrinogen alpha chain [P02671] | ELISA; WB | OSCC plasma marker | Plasma fibrinogen is a blood coagulation regulator associated with angiogenic and metastatic prediction in numerous tumors. | |
OSCC | 2D-DIGE; MALDI-TOF MS | Fibrinogen beta chain [P02675] | ELISA; WB | OSCC plasma marker | Blood-borne glycoprotein, functions in inflammatory responses. Showed elevated expression in OSCC samples. | [50] |
OSCC | 2D-DIGE; MALDI-TOF MS | Fibrinogen gamma chain [Q9UC63] | ELISA; WB | OSCC plasma marker | Gamma component of fibrinogen has a major function in homeostasis. Can be considered tumor marker, as the protein shows significantly higher expression in OSCC samples compared to the healthy ones. | [50] |
OSCC | 2D-DIGE; MALDI-TOF MS | Haptoglobin [P00738] | ELISA; WB | OSCC plasma marker | Plasma protein that binds to hemoglobin. Strong correlation was found between increasing levels of haptoglobin and clinical stages of OSCC. | |
OSCC | 2D-DIGE; MALDI-TOF MS | Leucine-rich alpha-2-glycoprotein/LRG1 [P02750] | ELISA; WB | OSCC plasma marker | This is involved in protein-protein interaction, signal transduction, cell adhesion and development. It is expressed during granulocyte differentiation. The expression was found up-regulated in the disease state. | [50] |
OSCC | 2D-DIGE; MALDI-TOF MS | RSK2/Ribosomal protein S6 kinase alpha-3 [P51812] | ELISA; WB | OSCC plasma marker | Plays a vital role in cellular and organismal physiology. Activation and elevation of RSK2 is associated with early events of tumorigenesis. | |
OSCC saliva | Cation exchange/reversed phase LC; 2D GE | S90K/Mac-2 binding protein (M2BP) | ELISA; WB; ROC | OSCC | M2BP, a tumor antigen was significantly up-regulated in nasopharyngeal carcinoma. | |
OSCC saliva | Cation exchange/reversed phase LC; 2D GE | S100-A9 | ELISA; WB; ROC | OSCC | It is a calcium-binding protein which is significantly overexpressed in saliva of OSCC patients. | |
OSCC saliva | Cation exchange/reversed phase LC; 2D GE | CD59 | ELISA; WB; ROC | OSCC | CD59 is one of the complement restriction factors that are overexpressed on the tumor cells and enable them to escape from complement-dependent and antibody-mediated killing. | |
OSCC saliva | Cation exchange/reversed phase LC; 2D GE | Profilin | ELISA; WB; ROC | OSCC | Profilin is regulator of the microfilament system. Overexpressed in tumor cells. Involved in various signaling pathways via interaction with cytoplasmic and nuclear ligand. | [88] |
OSCC saliva | Cation exchange/reversed phase LC; 2D GE | Catalase [P04040] | ELISA; WB; ROC | OSCC | Catalase protects the cells against oxidative stress. Altered levels are evident in human tumors and involved in carcinogenesis and tumor progression. | [88] |
OSCC saliva | Peptide free flow electro-phoresis; SCX | Signal transducer and activator of transcription 3 [P40763] | WB | OSCC | STAT3 mediates cellular responses to different growth factors. Expression of STAT3 demonstrate its role of development of OSCC. | [92] |
OSCC saliva | Peptide Free Flow Electro-phoresis; SCX | Thioredoxin-dependent peroxide reductase, mitochondrial [P30048] | WB | OSCC | Involved in redox regulation of cell. Expression of PRDX3 in whole saliva of patient confirmed the presence of the protein in saliva and can be considered a prospective biomarker of OSCC. | [92] |
OSCC saliva | Peptide Free Flow Electro-phoresis; SCX | Serpin B3 [P29508] | WB | OSCC | Modulates the host immune response against tumor cells. Plays tumor inhibitor role. | [92] |
OSCC saliva | 2D GE | Alpha-1 antitrypsin (AAT) | ELISA; IHC | OSCC | AAT is a serine protease inhibitor. The level of AAT increased in OSCC saliva. Useful for prediction of aggressive phenotypes in OSCC. | |
OSCC saliva | 2D GE | Complement C3 | ELISA; IHC | OSCC | Complement system helps antibodies fight of infections. Gauges the effectiveness of ongoing treatments for autoimmune disorder, cancers and infectious diseases. Level of C2 is proportional to aggression of tumor. | [93] |
OSCC saliva | 2D GE | Hemopexin [HPX] | ELISA; IHC | OSCC | HPX is plasma protein with highest binding affinity to heme. Distinctive high expression and tumor size parameter shows aggression of cancer. | [93] |
OSCC saliva | 2D GE | Transthyretin [TTR] | ELISA; IHC | OSCC | TTR is thyroid hormone-binding protein. Overexpressed in non-metastatic OSCC as compared to metastatic. | |
OSCC Saliva | MALDI-TOF MS | Zinc finger protein 510 (ZNF510) Zinc finger protein 142 (ZNF142) | IHC; ROC | OSCC | ZNF510 is involved in transcriptional regulation. Found to be expressed in high level in saliva of OSCC patients. | |
OSCC Saliva | 2D GE; MALDI-TOF | Transferrin | WB; ELISA | OSCC | Transferrin is an iron transport protein whose levels were found elevated in saliva. The level of salivary transferrin shows a relation with size and stage of the disease. | |
OSCC saliva | IHC | Lactate dehydrogenase (LDH) | ELISA | OSCC | LDH concentration in saliva indicate cellular necrosis. In an oral OSCC lesion, the level of salivary LDH is expected to increase as the mitotic rate also increases with the aggressiveness of the lesion. | [96] |
OSCC saliva | IHC | Cyclin D1 (CycD1) | ELISA | OSCC | CycD1 is a positive regulator of the transition from G1 to S phase in cell-cycle progression. Expression of CycD1 is amplified and over expressed in OSCC. | [96] |
OSCC saliva | IHC | Salivary carbonyls | ELISA | OSCC | Protein carbonyls are markers of oxidative stress. Increase in salivary carbonyl points at increased free radical attack. In malignant tissues the degree of oxidative DNA damage is increased whereas total anti-oxidant capacity is decreased. | [96] |
OSCC saliva | IHC | Mammary serine protease inhibitor (Maspin) | ELISA | OSCC | Maspin suppress tumor growth and progression, angiogenesis, invasion and metastasis in various malignancies including OSCC. | [96] |
OSCC saliva | IHC | 8-oxoguanine DNA glycosylase (OGG1) | ELISA | OSCC | Enzyme for repairing the oxidative DNA damage. Reduced activity of OGG1 is a risk factor for various cancers including OSCC. | [96] |
OSCC saliva | IHC | Phosphorylated-SRC | ELISA | OSCC | Src (a cytoplasmic kinase) drives adhesion changes that are associated with transition, proliferation and metastasis. It changes to phosphor-Src the inhibited form by oxidants by a reversible process. Src is expected to be increased while phosphor-Src is expected to be decreased to promote carcinogenesis in cancer patients. | [96] |
OSCC saliva | IHC | Ki-67 | ELISA | OSCC | A cell-cycle promoter that correlate with cellular proliferation, and tumor progression, metastasis and poor prognosis and are expected to increase in tumors. | [96] |
OSCC saliva | Immunoradiometric analysis | Carcinoembryonic antigen (CEA) | ELISA | OSCC | A type of glycoprotein produced by cells of gastrointestinal tract during embryonic development and involved in cell adhesion. Salivary and serum levels of CEA were found to be increased in malignant tumors than in healthy tissues. | [97] |
OSCC saliva | Immunoradiometric analysis | Carcinoma associated antigen (CA 50) | ELISA | OSCC | A cancer-associated carbohydrate marker. CA50 is not organ-specific and its elevated levels in serum can be seen in variety of malignancies. CA 50 in saliva and serum showed significantly high levels in malignant tumors as compared to the healthy normal tissues. | [97] |
OSCC saliva | Radial immunodiffusion | Insulin growth factor-1 (IGF-1) | ELISA | OSCC | IGF plays significant role in carcinogenesis by modifying cancer-cell proliferation, survival, growth and apoptosis. Salivary IGF level was shown to be substantially raised in cancer patients. | [96] |
OSCC saliva | Radial immunodiffusion | Metalloproteinase (MMP2) | ELISA | OSCC | Metalloproteinases participates in cancer pathogenesis by degrading type-IV collagen, elastin, and fibronectin. Highly expressed in stromal cells surrounding the invading front of metastasizing tumors and their levels are elevated in tumor endothelium. | |
OSCC saliva | Radial immunodiffusion | Metalloproteinase (MMP9) | ELISA | OSCC | Level of MMP-9 showed an increase in OSCC patients. | |
OSCC saliva | WB;PCR | CD44 and soluble CD44 | ELISA | OSCC | CD44 shows elevation in majority of HNSCC. Distinguishes cancer from benign disease with high specificity. | |
OSCC Serum and Saliva | 2-D gel electrophoresis | Tetranectin | Liquid chromatography/tandem mass spectrometry | Lymph node involvement | Plasminogen-binding protein with a C-type lectin domain may be involved in packaging molecules for exocytosis | [102] |
OSCC Saliva | ELISA | Interleukin 1b (IL1b) | ELISA | Carcinogenesis | Cytokine mediator of inflammatory response | |
OSCC saliva | ELISA | Interleukin 8 (IL8) | ELISA | Carcinogenesis | Chemoattractant cytokine mediates inflammatory response | |
OSCC Saliva | ELISA | Mac-2 binding protein (M2BP) | ELISA | Carcinogenesis | Cell-adhesive protein of the extracellular matrix which self-assembles into ring-like structures and binds beta1 integrins, collagens, and fibronectin | [103] |
OSCC saliva Plasma | 2DE | Apolipoprotein A1 APOA1 | MS | Differentiate from leukoplakia | As component of HDL participate in lipid metabolism | |
OSCC saliva | 2DE | Alpha amylase | MS | Differentiate from leukoplakia | Hydrolyses alpha bonds of large, alpha-linked polysaccharides, such as starch and glycogen, yielding shorter chains thereof, dextrins, and maltose, normally present in saliva | [108] |
OSCC saliva | 2DE | cystatins | MS | Differentiate from leukoplakia | Cysteine protease inhibitors | [108] |
OSCC saliva | 2DE | Keratin 10 | MS | Differentiate from leukoplakia | Intermediate filament protein of cytokeratin family. Fibrous protein forming the cellular framework | [108] |
OSCC saliva | LC-MRM/MS | Alpha-1-acid glycoprotein (A1AG1; AGP1; OMD1) | MS | Carcinogenesis | Inflammatory acute phase reactant | [110] |
OSCC saliva | LC-MRM/MS | Alpha-1-antitrypsin A1AT | MS | Carcinogenesis | Protease inhibitor | [110] |
OSCC saliva | LC-MRM/MS | Alpha-1-B Glycoprotein | MS | Carcinogenesis | Glycoprotein of unknown function | [110] |
OSCC saliva and plasma | MS | Matrix metaaloprotein 1 (MMP1) | MS | Carcinogenesis | Interstitial collagenase and fibroblast collagenase participate in breakdown of extracellular matrix | |
OSCC saliva and plasma | MS | Matrix metaaloprotein 3 (MMP3) Stromelysin-1 | MS | Carcinogenesis | Interstitial collagenase and fibroblast collagenase participate in breakdown of extracellular matrix. degrades collagen types II, III, IV, IX, and X, proteoglycans, fibronectin, laminin, and elastin | [111] |
OSCC saliva | iTRAQ | Complement factor H (CFH) | MS | Carcinogenesis | Regulators of complement activation family | [84] |
OSCC saliva | Luminex-based multiplex | Tumor necrosis factor (TNF) | Carcinogenesis | Cytokine used by immune system for cell signaling | [104] | |
OSCC saliva | Luminex-based multiplex | Vascular endothelial growth factor (VEGF) | Carcinogenesis | Signaling protein that promotes angiogenesis | ||
OSCC saliva | MS | Actin | MS | Carcinogenesis | Multi-functional protein form microfilaments in the cytoskeleton | [113] |
OSCC Saliva | MS | Myosin | MS | Carcinogenesis | Motor proteins that interact with actin. | |
OSCC blood | ELISA, IHC MALDI-TOF-MS | C-reactive protein (CRP) | ELISA, IHC, MS | Carcinogenesis | A protein whose concentration increase in response to inflammation—acute phase protein | |
OSCC blood | ELISA, IHC | Leucine-rich alpha-2-glycoprotein (LRG) | ELISA, IHC | Carcinogenesis | Acute phase protein | [114] |
OSCC saliva | 2D-GE | Zinc-alpha-2-glycoprotein (ZAG) | MS | Carcinogenesis | Participate in glycolipid metabolism | [115] |
OSCC saliva | 2D-GE | Peroxiredoxin-2 (PRDX-2) | MS | Carcinogenesis | Catalyzes the reduction of peroxides | |
OSCC saliva | LC-MS/MS | α-2-Macroglobulin-like protein 1 | MS | Carcinogenesis | Inhibitor of proteases, role in auto immune diseases | [117] |
OSCC saliva | LC-MS/MS | Kininogen -1 | MS | Carcinogenesis | Cofactor for the activation of prekallikrein, factor XII and factor XI | [117] |
OSCC saliva | SDS-PAGE and MALDI TOF/TOF | Annexin A8 | MS | Carcinogenesis | Participate in membrane-cytoskeleton dynamics | [116] |
OSCC Saliva | ELISA | IL6 | ELISA | Carcinogenesis | Acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine | [118] |
OSCC plasma | MALDI-TOF | GIMAP7 GTPase, IMAP Family Member 7 | MS | Carcinogenesis | Regulators of lymphocyte survival and homeostasis, GTP Binding | [119] |
OSCC plasma | MALDI-TOF | Rabl3 RAB like protein 3 | MS | Carcinogenesis | Unknown function, supposed to participate in cellular regulation | [119] |
OSCC plasma | MALDI-TOF | Heat shock protein 90 (HSP 90) | MS | Carcinogenesis | Cell cycle control, cell survival, hormone and other signaling pathways | [120] |
OSCC saliva | SDS Page | Resistin adipose tissue-specific secretory factor (ADSF) or C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein (XCP1) | LS-MS | Carcinogenesis | Increases production of LDL | [121] |
OSCC brush biopsy | MS | Secretory leukocyte protease inhibitor | MS | Carcinogenesis | Anti-microbial and anti-inflammatory, found in saliva, breast milk, etc. | [122] |
OSCC serum | ELISA | Guanylate-binding protein 1 (GBP1) | ELISA | Carcinogenesis | Regulation of membrane, cytoskeleton, and cell cycle progression | [123] |