Table 1.
Biomarkers in solid biopsy and liquid biopsy.
| Biomarker in Tissues | Note | Sample Size/References |
| Up: PCNA | Cell proliferation | 30 OSF, 10 OSCC [78] |
| Up: cyclophilin A | Cell proliferation | 25 normal, 25 OSF [79,80] |
| Up: NCOA7 | Cell proliferation, early diagnosis of OSF malignant transformation | 24 OSF tissues without malignant transformation, 34 OSCC tissues arising from OSF [81] |
| Up: HIF-1α, PAI-1 | Angiogenesis | 6 normal, 25 OSF [58] |
| Up: CD105 | Angiogenesis | 15 normal, 30 OSF [82] |
| Up: α-enolase | Cell proliferation, tumorigenesis (increased Warburg effect) | 13 normal, 19 OSF without dysplasia (OSFWT), 23 OSF with dysplasia (OSFWD), 28 OSCC [83]. |
| Up: Ki67, cyclin D1, c-Met, IMP3Down: β-catenin | Cell proliferation (Ki67, cyclin D1), invasion (c-Met, IMP3), the combined biomarkers of Ki67 and p16 (tumor suppressor) showed significantly different expression between the transformation and non-transformation groups | 6 normal, 36 OSF [84] |
| Down: WIF1 | Wnt antagonist, inhibits Wnt/β-catenin signaling by directly binding to Wnt proteins. | 15 normal tissue, 45 OSF, 55 OSCC [85] |
| Up: β-catenin Down: SFRP-1, SFRP-5 |
Wnt/β-catenin signaling | 15 normal, 45 OSF, 55 OSCC [86] |
| Down: miR-200b, miR-200c Up: ZEB1, ZEB2 |
miR-200b targeting ZEB2, miR-200c targeting ZEB1 | 25 control, 25 OSF [87] 20 control, 20 OSF [88] |
| Down: LncRNA GAS5-AS1 | LncRNA GAS5-AS1 bind to Smads and prevents them binding to SBE on TGF-β target gene promoter, thereby negatively regulates TGF-β/Smad signaling pathway | 25 control, 25 OSF [89] |
| Up: LncRNA LINC00974 | LncRNA LINC00974 activates TGF-β/Smad signaling | 20 OSF tissues [48,90] |
| Biomarker in Serum | Note | Sample Size/References |
| Down: Serum protein, globulin | - | 50 control, 50 nicotina stomatitis, 50 OSF, 50 leukoplakia, 50 malignancy [91] |
| Up: Copper | Serum copper levels increased gradually from precancer to cancer, as the duration of betel quid chewing habit increased. | 30 control, 30 OSF, 30 OSCC [92] |
| Up: Sister chromatid exchange in lymphocytes | Genotoxic, genome instability, | 10 male patients who had the habit of chewing pan for 5 or more years, 10 male patients with OSF who had panparag chewing habit and 10 age- and sex-matched controls without any chewing habit [93] |
| Down: β-carotene | β-carotene as the best-known provitamin A carotenoid | 40 control, 40 OSF [94] |
| Down: E-SOD, GPx | Anti-ROS stress | 25 control, 25 OSF, 25 leucoplakia, 25 OSCC [95] |
| Up: LDH | Cell metabolism | 30 control, 30 OSF [96] 20 control, 20 OSF [97] |
| Up: MDA, comet assay | ROS product (MDA), DNA damage phenotype (comet assay) | 30 control, 30 OSF [98] |
| Biomarker in Saliva | Note | Sample Size/References |
| Up: 8-OHdG, MDADown: Vitamin C, vitamin E | ROS product (8-OHdG, MDA), anti-ROS stress (vitamin C, vitamin E) | 40 OSCC, 40 oral lichen planus lesions, 40 leukoplakia, 40 OSF, 40 control [99] |
| Down: GPx, SOD | Anti-ROS stress | 63 control, 63 OSF [100] |
| Up: LDH | LDH main function is to catalyze the oxidation of lactate to pyruvate. | 30 control, 30 OSF [96] 20 control, 20 OSF [97] 10 control, 25 OSF, 25 OSCC [101] |
| Up: S100A7 | A small calcium-binding protein, has been associated with the development of psoriasis and carcinomas in different types of epithelia. | 30 control, 30 OSF [102,103,104] |
| Instrument | Note | Sample Size/References |
| Auto-fluorescence spectroscopy, (320–330 nm excitation, collagen at 380–400 nm emission and NADH at 440–460 nm emission) | Up: Collagen Down: NADH |
15 normal oral mucosa, 59 OSF mucosal [105]. 18 normal individuals without the habit of betel quid chewing, 18 betel quid chewers without OSF, 15 OSF [106]. 20 normal, 20 OSF [107]. |
| OCT detect the epithelium thickness and the standard deviation of A-mode scan intensity in the laminar propria layer | Up: Epithelium thickness, laminar propria layer | 44 OSF samples were obtained from 44 patients. Also, 44 healthy samples were obtained from 26 healthy volunteers. [108] |
| FTIR spectrometry | Protein contents in serum were different | 30 control, 30 OSF [109] |