Table 1 Potential protein tissue biomarkers of head and neck cancers
From: A systematic review of proteomic biomarkers in oral squamous cell cancer
Sample | Technique | Biomarker [accession no.] | Confirmation by | Biomarker for | Discussion | Reference |
|---|---|---|---|---|---|---|
OSCC | RPLC-MS/MS: MS | Desmoglein-3 [P32926] | IHC | Carcinogenesis | Desmoglein 3 maintains structural integrity preferentially in oral epithelium. Changes in their relative levels might represent putative biomarkers of disease progression. | [18] |
OSCC | RPLC-MS/MS: MS | Cytokeratin 4 [P190013] | IHC | Carcinogenesis | Expressed predominantly in suprabasal-nonkeratinizing layer of stratified epithelium of control normal tissues, whereas OSCC was restricted to only few well differentiated tumors. | |
OSCC | RPLC-MS/MS: MS | Cytokeratin 16 [P08779] | IHC | Carcinogenesis | Present in suprabasal layer of oral squamous epithelium in the normal tissue, whereas OSCC expresses positive in most moderate to well-differentiated cells | |
OSCC | RPLC-MS/MS: MS | Desmoplakin [P15924]; | IHC | Carcinogenesis | Predominantly membranous with high immunoreactivity in suprabasal areas of squamous epithelium in normal tissues, whereas OSCC expresses dominantly along the well-differentiated areas of tumor cells | |
OSCC | RPLC-MS/MS: MS | Vimentin [P08670] | IHC | Carcinogenesis | Involved in epithelial-mesenchymal transition. Malignant squamous cells in tumor cells show high immunoreactivity to vimentin as in contrast to a few isolated normal cells. | |
OSCC | IMAC30 protein arrays; SELDI-TOF MS | α-Defensins 1-3 [DEF1-3] | Tissue microarray; IHC | Tumor relapse | Major constituent of azurophilic granules of neutrophils. Normally do not express in epithelia. Plays vital role in mucosal innate immune defense to infectious diseases including epithelial cancers. In OSCC, increased expression of α defensin 1-3 has been described in neutrophils that infiltrate OSCC. In healthy mucosa defensin expression is limited to submucosal neutrophil granulocytes. Represents an important link between inflammation, angiogenesis, and cancer. | [25] |
OSCC | 2D DIGE | Keratin 4 [P19013] | IHC; ROC; KMS | OSCC premalignant tissue and second field cancer tissue Prognostic | Low expression of keratin 4 in resection margins of surgically treated OSCC patients accurately predicts local relapse. Loss of keratin 4 expression is a valuable enrolment criterion for tertiary prevention trials in treated OSCC patients. | |
OSCC | 2D DIGE | Keratin 13 [P13646] | IHC; ROC; KMS | OSCC premalignant tissue and second field cancer tissue | Keratin 13 is a protein involved in differentiation process, expression of which changes during the carcinogenic process. Keratin 13 and keratin 4 are such dimers that aggregate to form intermediate filaments of cytoskeleton in epithelial cells. | |
OSCC | 2D DIGE | Cornulin [Q9UBG3] | IHC; ROC; KMS | OSCC premalignant tissue and second field cancer tissue | Loss of expression in the surgical margin predicts the risk of local relapse. | [19] |
OSCC | 2D DIGE | Small proline-rich protein 3 [Q9UBC9] | IHC; ROC; KMS | OSCC premalignant tissue and second field cancer tissue | Expresses high in normal mucosa and low in tumors. Belongs to protein group forming cornified envelope, which is an important protective barrier of mucosa and skin and is involved in the differentiation process. | [18] |
OSCC | 2D GE iTRAQ/MDLC | Stratifin [P31947] | IHC WB; rt-PCR; Co-immunoprecipitation assays; ROC; KMS | OSCC | Overexpressed in HNSCC. Stratifin protein recognizes phosphoserine/threonine-containing motifs to bind target proteins that play important roles in regulation of various cellular processes, including regulation of oncogenes and tumor suppressor genes in carcinogenesis | |
OSCC | iTRAQ/MDLC | YWHAZ 14-3-3 zeta/delta [P63104] | IHC; WB; rt-PCR; Co-immuno precipitation assays; ROC; KMS | OSCC | Overexpressed in different stages of development of OSCC. Involved in cell signaling pathways in inflammation, cell proliferation and abrogation of apoptosis during oral carcinogenesis. Stratifin-YWHAZ heterodimer may serve as a plausible therapeutic strategy by using a small molecule modulator/peptide inhibitor that intervenes with 14-3-3 client protein interactions. | |
OSCC | iTRAQ/MDLC | S100-A7 [P31151] | IHC; WB; rt-PCR; Co-immuno precipitation assays; ROC; KMS | Prognostic | A calcium-binding protein, originally identified in psoriatic keratinocytes and is upregulated in abnormally differentiated keratinocytes. Also identified in oral premalignant epithelium and is proposed to be a marker for invasion. | |
Oral premalignant (leucoplakia) | iTRAQ | hnRNPK [P61978] | IHC; WB; rt-PCR; ROC | Epithelial dysplasia (leukoplakia) | Heterogeneous nuclear ribonucleoprotein K is an RNA-binding protein that regulates gene expression at both transcriptional and translational level. It directly regulates the expression of COX2, implicated in the synthesis of prostaglandins, which are mediators of inflammatory response. hnRNPK is overexpressed aberrantly localized, whose transcriptional upregulation as reported in OSCC. | |
Oral premalignant (leucoplakia) | iTRAQ | PTHA [P06454] | IHC; WB; rt-PCR; ROC | Epithelial dysplasia (leukoplakia) | Prothymosin alpha, overexpressed in oral premalignant lesions, proposed to be a proliferation marker of thyroid cancer. | |
OSCC | 16O/18O-labeling; 2DLC | Thymidine phosphorylase [TYPH] [p19971] | WB; IHC | Tissue markers for OSCC | TYPH is overexpressed in wide variety of solid tumors and can be induced by several cytokines and contributes to angiogenesis. | |
OSCC | 16O/18O-labeling; 2DLC | Filamin-A [P21333]; | WB; IHC | Tissue markers for OSCC | Filamin A is involved in organization of extracellular matrix that assists the exchange of signals. Overexpressed in OSCC and is reported as a target for DNA-damage based cancer therapy. | |
OSCC; OSCC | 16O/18O-labeling; 2DLC | Fascin [Q16658] | WB; IHC | Tissue markers for OSCC | Fascin is a globular actin-cross-linking protein that forms parallel actin bundles in cell protrusions. Fascin overexpression promotes cancer progression via AKT and MAPK pathways in OSCC. | |
OSCC | 16O/18O-labeling; 2DLC | Carbonic anhydrase 2 [P00918] | WB; IHC | Tissue markers for OSCC | Carbonic anhydrases catalyze the equilibrium of carbon dioxide and carbonic acid. Found to be overexpressed in OSCC and can be used to predict local tumor growth in OSCC. | |
OSCC | 2D GE; Coomassie | Rack1 [P63244] | WB; IHC; RT-PCR; Rack1 si-RNA | Severe dysplasia | Originally identified as anchoring protein for protein kinase C, highly conserved among all eukaryotes and linked to translation initiation in all organisms. Overexpression of RACK 1 in OSCC cancer cell lines suggests potential oncogenic property for RACK1 in oral carcinogenesis. | [45] |
OSCC | LC-MS | Keratin 13 [gi62897663] | WB; IHC; rtPCR; | OSCC | Cancer demonstrated down regulation of keratin 13 in OSCC. Aberrant expression indicates dysregulation and cellular transformation of epithelial cells in OSCC. | [46] |
OSCC | LC-MS | Keratin 4 [109225249] | WB; IHC; rtPCR; | OSCC | Keratin 4 expression was found to be significantly decreased in OSCC samples. Low expression of keratin 4 is associated with morphological changes in affected oral epithelium and can cause changes in cell shape and movement. | [46] |
OSCC | LC-MS | Transglutaminase 3 [gi80478896] | WB; IHC; rtPCR | OSCC | Significantly down regulated in cancer and correlated with loss of histological differentiation. Reduction in transglutaminase 3expression is related with dedifferentiation, increase in invasive phenotype and poor prognosis. | [46] |
OSCC tongue cancer | LC-MS | Annexin I [gi442631] | WB; IHC; rtPCR | OSCC Carcinogenesis | Glucocorticoid-inducible protein, Annexin I has emerged as an important endogenous modulator of inflammation. Evident downregulation of ANXA1 in the cancerous lesions was observed. | |
OSCC | 2D GE | Enolase1 [P06733] | IHC; rt-PCR | OSCC | Glycolytic enzyme present in cytoplasm, acts as plasminogen receptor on the surface of cells. Detection of enolase 1 was observed significantly higher in OSCC patient saliva compared to healthy individuals. Useful as biomarker for OSCC. | [50] |
Tongue cancer | 2D-DIGE | Cofilins | nLC-MS/MS | Carcinogenesis | Actin binding protein participate in cellular motility severing actin filament, nucleating, depolymerizing, and bundling activities | |
Tongue cancer | 2D-DIGE | Myosin light chain family members | nLC-MS/MS | Carcinogenesis | Myosin light chains are members of the calmodulin (CaM) and CaM-related gene families involved in the mechanoenzymatic function of the myosin holoenzyme | |
Tongue cancer | 2D-DIGE | Annexin 5 | nLC-MS/MS | Carcinogenesis | Member of the calcium and phospholipid binding protein family act as immune check point inhibitor and tumor homing molecule | [47] |
Tongue cancer | 2D-DIGE | HSP A8 | nLC-MS/MS | Carcinogenesis | Heat shock cognate 71 act as repressor of transcriptional activator | |
Tongue cancer | 2D-DIGE | Carbonic anhydrase 1 (CA1) | nLC-MS/MS | Carcinogenesis | Carbonic anhydrases 1 belong to family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide | [47] |
Tongue cancer | 2D-DIGE | HSP5a (HSP70) Heat shock protein family A (HSP 70) member 5 | nLC-MS/MS | Carcinogenesis | Post-translational transport of small presecretory proteins across endoplasmic reticulum | |
Tongue cancer | 2D-DIGE | Serpin B3 | nLC-MS/MS | Carcinogenesis | Papain-like cysteine protease inhibitor to modulate the host immune response against tumor cells | [47] |
Tongue cancer | 2D-DIGE | Tropomyosin alpha-4 chain TPM 4 | nLC-MS/MS | Carcinogenesis | Binds to actin filament and participate in muscle contraction along with troponin complex and calcium dependent regulation | [47] |
Tumor | IHC | Cystanin B | Targeted proteomics | Prognostic | Cysteine protease inhibitors | [54] |
OSCC | iTRAQ | Gelsolin | Immunoassay | Prognostic | Actin-modulating protein that participate in severing, and capping cytoskeletal actin | [55] |
OSCC | iTRAQ | Fibronectin | Immunoassay | Prognostic | Extracellular matrix glycoprotein binds to integrins | [55] |
OSCC | iTRAQ | Haptoglobin | Immunoassay | Prognostic | Acute phase protein capable of binding hemoglobin | |
OSCC | IHC | Prothymosin α (PTMA) | IHC | Prognostic | Major component of Thymosin Fraction 5 enhances cell-mediated immunity in humans | [33] |
OSCC | IHC | Heterogeneous nuclear ribonucleoproteinK (hnRNPK) | IHC | Prognostic | Binds to pre-messenger RNA as a component of heterogeneous ribonucleoprotein particles controls cell cycle progression | [33] |
OSCC | Rho GDP-dissociation inhibitor alpha (RhoGDIα) | Prognostic | Regulates the GDP/GTP exchange reaction of the Rho proteins by inhibiting the dissociation of GDP and binding of GTP | |||
OSCC | 2D-PAGE/MS | Annexin A2 | MS | Carcinogenesis | Involved in cell motility, linkage of membrane-associated protein complexes to the actin cytoskeleton, endocytosis, fibrinolysis, ion channel formation, and cell matrix interactions | [58] |
OSCC | MS | Complement component C7 | MS | HPV-induced carcinogenesis | Membrane attack complex (MAC) protein that plays a role in the innate and adaptive immune response | [59] |
OSCC | MS | Apolipoprotein F (ApoF) | MS | HPV-induced carcinogenesis | Sialoglycoprotein resides on the HDL and LDL fractions of plasma | [59] |
OSCC | MS | Galactin 3-binding protein | MS | HPV-induced carcinogenesis | Glycoprotein induced by inflammatory cytokines and interleukins | [59] |
OSCC | AMIDA | Cytokeratin 8 | Carcinogenesis | One of the keratin proteins associated with secretary epithelium | [60] | |
OSCC | 2D-GE | Heat shock protein 60 | MS | Carcinogenesis | Also known as chaperonin prevent misfolding of proteins | [61] |
OSCC | 2D-GE | Heat shock protein 27 | MS | Carcinogenesis | Also known as HSP B1 participate in thermotolerance, inhibition of apoptosis, regulation of cell development, and cell differentiation | [61] |
OSCC | GeLC-MS/MS | Nidogen 1 (NID1) | IHC | Carcinogenesis | Known as entactin is a component of the basement membrane | [62] |
OSCC | Thrombospondin 2 (THBS2) | Prognosis | Mediates cell-to-cell and cell-to-matrix interactions | [63] | ||
OSCC | IHC | End-binding protein (EB1) | IHC | Carcinogenesis | Regulate microtubule dynamics | [64] |
OSCC | IHC | S100 A2 | IHC | Carcinogenesis | Induced by p53, contribute to transcription of p21, differentiation and regeneration | |
OSCC | IHC | Scara5 | IHC | Carcinogenesis | Act as ferritin receptor found in many cancers | [67] |
OSCC | IHC | S100 A8 | IHC | HPV-induced carcinogenesis | Calcium- and zinc-binding protein regulator of inflammation and modulate immune response | |
OSCC | IHC | Galactin 7 | IHC | Carcinogenesis | β-galactoside sugar 15 different types are known | [70] |
OSCC | IHC | Survivin | IHC | Carcinogenesis | Inhibitor of apoptosis protein | [71] |
OSCC | IHC | SCC antigen | IHC | Carcinogenesis | Tumor-associated antigen present in cases of SCC | [71] |
OSCC | Keratin 1 | Carcinogenesis | Expressed in epidermis interaction with other genes is known | [48] | ||
OSCC | IHC | P53 | IHC | Carcinogenesis | Protein product of tumor suppressor gene, participate in DNA repair | [72] |
OSCC | IHC | Deleted in liver cancer (DLC1) | IHC | Carcinogenesis | Protein product of tumor suppressor gene regulates Rho GTPase-activating protein (GAP) domain | [73] |
OSCC | IHC | Carcinoembryonic antigen-related adhesion molecule 1 (CEACAM1) | IHC | Carcinogenesis | Mediates cell adhesion by homo and heterophilic bindings | [74] |
OSCC | 2DE | Proteosome activator PA28 a, b and g | MS | Carcinogenesis | Protein activator of the 20 S proteasome | [75] |
OSCC | MALDI TOF | NCOA7 | IHC | Carcinogenesis | Nuclear receptor coactivator 7 enhances transcriptional activities and coactivate several other nuclear receptors | [76] |
OSCC | IHC | C6orf141 (chromosome 6 open reading frame 141) | IHC | Carcinogenesis | Cell membrane protein found in many cancers, associated with prognosis of breast and endometrial cancer. | [77] |
OSCC | IHC | SOD2 superoxide dismutase 2 | IHC | Lymph node metastasis | Member of the iron/manganese superoxide dismutase family | [78] |
OSCC | IHC | BST2 bone marrow stromal cell antigen 2 | IHC | Lymph node metastasis | Acts as a direct physical tether, holding virions to the cell membrane and linking virions to each other. | [78] |
OSCC | IHC | ITGB6 integrin subunit beta 6 | IHC | Lymph node metastasis | Receptor for fibronectin and cytotactin | [78] |
OSCC | IHC | PRDX4 peroxiredoxin-4 | IHC | Lymph node metastasis | Member of the peroxiredoxin family of antioxidant enzymes | [78] |
OSCC | MALDI | LRP6 low-density lipoprotein receptor-related protein 6 | IHC | Carcinogenesis | Coreceptor of Wnt/beta-catenin signaling | [79] |
OSCC | Bioluminescence | Lactate dehydrogenase (LDH) | Bioluminescence | Carcinogenesis | Catalyzes the conversion of lactate to pyruvate and back | [80] |