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. 2023 Dec 10;96(1):250–280. doi: 10.1111/prd.12542

TABLE 2.

Protein‐based biomarkers for OSCC.

Author/Year Source of biomarkers Method Sample size Proteins identified Findings
Riccardi et al. 57 Saliva Systematic Review N/D IL‐1α, IL‐1β, IL‐6, IL‐8, IL‐1Ra, IL‐10, TNFα, VEGF‐α, MMP1, MMP2, MMP3, MMP9, AATα, HAPβ, C3, hemopexin, serotransferrin, transthyretin, fibrinogen β, resistin and proline‐rich proteins (a, b and g) Increased in OSCC compared to Control.
Pillai et al. 116 Saliva and Serum Systematic review N/D EGFR, Vitamin D‐binding protein, Fibrinogen, CEA, Increased in OSCC compared to Control.
Arroyo et al. 70 Saliva Systematic review and meta‐analysis 986 CEA, CRP, CYFRA‐21‐1, Her‐2/neu, erbB‐2, IL‐1α, IL‐1β, IL‐6, IL‐8, TNF α and Naa10p Increased in OSCC and OPMD compared to Control for CEA and CYFRA21‐1 only
Ferrari et al. 71 Saliva Systematic review 948 IL‐6, IL‐8, IL‐17, IL‐1β, TNF‐α, IFN‐γ, MIP‐1β, GRO, VEGF and IP‐10 OSCC > OPMD > Control
AlAli et al. 194 Saliva Systematic review 775 CYFRA 21‐1 and MMP‐9 Non‐conclusive evidence due to the presence of biases and limitations in the studies evaluated
Dikova et al. 195 Saliva Multiplex ELISA 157 IL‐1α, IL‐6, IL‐8, TNF‐α, HCC‐1, MCP‐1 and PF‐4 OSCC > OPMD > Control
Sivadasan et al. 196 Saliva ELISA 67 CD44 OSCC > OPMD > Control
Ameena et al. 197 Saliva ELISA 90 TNF‐α OSCC > OPMD > Control
Deepthi et al. 198 Saliva ELISA 90 TNF‐α OSCC > OPMD > Control
Zheng et al. 62 Saliva and Serum ELISA 202 CEA, Naa10p

OSCC > OPMD > Control

Salivary detection had the greatest sensitivity and specificity compared to Serum
Lee et al. 199 Saliva Multiplex ELISA 65 IL‐6, IL‐8, IL‐1β, TNF‐α, IFN‐γ, MIP‐1β, Eotaxin and GRO Increased in OSCC compared to Control
Abbas et al. 200 Saliva ELISA 50 IL‐17 Increased in OSCC compared to Control
Seyedmajidi et al. 201 Saliva and Serum ELISA 40 CD44 Increased in OSCC compared to Control, although not statistically significant
Awasthi et al. 202 Saliva ELISA 64 CYFRA 21‐1 and LDH Increased in OSCC and OPMD compared to Control
Amylase Increased in Control compared to OSCC and OPMD
Khyani et al. 68 Saliva ELISA 105 IL‐6 and IL‐8 Increased in OSCC and OPMD compared to Control
Peisker et al. 203 Saliva ELISA 60 MMP‐9 Increased in OSCC compared to Control
Yu et al. 204 Saliva LC–MS 478 MMP1, KNG1, ANXA2 and HSPA5 Increased in OSCC compared to OPMD and Control
Polz‐Dacewicz et al. 205 Saliva ELISA 118 IL‐10, TNF‐α, TGF‐β and VEGF Increased in OSCC compared to Control
Gleber‐Netto et al. 206 Saliva ELISA 180 IL‐1β and IL‐8 OSCC > OPMD > Control
Dineshkumar et al. 207 Saliva ELISA 300 IL‐6 OSCC > OPMD > Control
Ghallab & Shaker 208 Saliva and Serum ELISA 45 Chemerin and MMP‐9 OSCC > OPMD and Control
Rajkumar et al. 63 Saliva and Serum ELISA 200 CYFRA 21‐1

OSCC > OPMD > Control

Salivary CYFRA 21‐1 levels were three‐fold higher when compared to serum levels
Aziz et al. 209 Saliva Multiplex ELISA 63 IL‐10 and IL‐13 Increased in OSCC compared to Control
Gautam et al. 61 Plasma nanoLC‐MS/MS 28 CRP, Fibrinogen alpha and Beta Chains, Fibronectin‐1, Serum amyloid A‐1, C4b‐binding protein beta chain Increased in OSCC compared to Control up to 5.36‐fold
Catalase, Flavin reductase, Carbonic anhydrase 1 and 2, SOD1, Purine nucleoside phosphorylase, APOA4, Desmoplakin, Desmoglein‐1, Lumican Decreased in OSCC compared to Control up to 4.28‐fold
Zhang et al. 210 Serum Protein Microarray Assay 50 GDF15, MCSF, I309, MMP‐3, CTACK, AXL Increased in OSCC compared to Control
Schiegnitz et al. 69 Serum ELISA 205 IL‐6 and IL‐8 Increased in OSCC compared to OPMD and Control
Xu et al. 66 Serum, Tissue Western blot 68 GLUT‐1 Increased in OSCC compared to Control
Ramos‐García et al. 211 Tissue Systematic review and meta‐analysis 1210 p53 OSCC > OPMD > Control
Ramos‐García & González‐Moles 212 Tissue Systematic review and meta‐analysis 2746 β‐Catenin

Increased aberrant expression in OSCC compared to control

Aberrant Expression ‐ Aggregated Hazard Ratio 1.77

Membrane loss – Aggregated Hazard Ratio 2.29
Botha et al. 67 Tissue and cell lines Systematic review N/D GLUT‐1, GLUT‐3, Increased in OSCC compared to Control
GLUT‐2, GLUT‐4, GLUT‐8, GLUT‐13, SGLT‐1 and SGLT‐2 Not significantly difference
Upadhaya et al. 213 Tissue Immunohistochemistry 40 ZO‐1 and E‐cad Control > OPMD > OSCC
Ghazi et al. 64 Tissue Immunohistochemistry 55 CD44 OSCC > OPMD > Control
Zhang et al. 214 Tissue Immunohistochemistry 178 p53, Ki‐67, P16, β‐catenin, c‐jun, c‐met, IMP‐3, COX‐2, PDPN, CA9 Increased in OSCC compared to Control
Gissi et al. 215 Tissue Immunohistochemistry 77 p53 and Ki‐67 Increased in OSCC compared to Control
Mumtaz et al. 216 Cell line/Tissue NanoLC‐MS/MS 14 Transferrin receptor, THBS2, LGALS3BP and DNAJB11 Increased in OSCC compared to Control

Abbreviations: AXL, receptor tyrosine kinase; CA9, carbonic anhydrase 9; CEA, Carcinoembryonic Antigen; CEA, Carcinoembryonic Antigen; COX‐2, cyclooxygenase‐2; CTACK, cutaneous T cell‐attracting chemokine; CYFRA 21, cytokeratin‐19 fragment; MCP‐1, monocyte chemoattractant protein‐1; MIP‐1β, Macrophage Inflammatory Protein‐1 beta; MMP‐1, Matrix metallopeptidase 1; MMP‐3, Matrix metallopeptidase 3; MMP‐9, Matrix metallopeptidase 9; N/D, not disclosed; Naa10p, N‐α‐acetyltransferase 10 protein; Naa10p, N‐α‐acetyltransferase 10 protein; OPMD, Oral Potentially Malignant Disorders; OSCC, Oral Squamous Cell Carcinoma; PDPN, podoplanin; PF‐4, platelet factor‐4; VEGF, Vascular endothelial growth factors.