| Mechanism | Gene | Gene function | Clinicopathological associationa | References |
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Cell cycle regulation | CYCA1 | Cell cycle | Lower histological grade | [37, 47] | CHFR | Early G2/M checkpoint | Higher T status | [48, 49] | p14ARF | Proapoptosis | LNMb, T status (T2-3), advanced stage Reduced recurrence rate, favourable prognosis | [32, 40–42, 50, 51] | p15 | Cyclin-dependent kinase inhibitor 2B | Anatomic site (tongue SCC) Alcohol and tobacco use | [35, 41, 50] | p16INK4A | Regulates cell cycle G1 progression | Larger tumor size, LNM, advanced stage Younger age, increased recurrence rate, poor prognosis | [29, 30, 32–35, 37, 40–42, 50, 52–54] |
| DNA repair | hMSH1/hMSH2 | DNA mismatch repair | — | [35, 38, 55] | MGMT | Guanine alkylation repair | Reduced overall survival Reduced disease-free survival | [29, 35, 38, 56] |
| Signal transduction | EDNRB | Endothelin receptor type B | Alcohol and tobacco use | [30, 34] | RUNX3 | Wnt pathway antagonist | LNM, advanced stage, poor differentiation | [34, 38, 57, 58] | SFRP1 | Wnt pathway antagonist | Male gender | [59] |
| Tissue invasion/metastasis | ECAD | Calcium-dependent cell-cell adhesion glycoprotein | LNM, increased metastatic potential Reduced disease-free survival | [35, 60–62] |
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Tumor suppression | HIN1 | Inhibitor Ras pathway | Reduced disease-free survival | [63] | DAPK1 | Proapoptosis | LNM | [38, 41] | DCC | Proapoptosis | Invasion of bone and deep tongue Reduced survival | [30, 41] | RASSF1A/RASSF2 | Negative RAS effector, proapoptotic, microtubule stabilization | Decreased disease-free survival radioresistance | [38, 63] |
| Other | KIF1A | Cell division and microtubule-dependent intracellular organelle transport | Malignant histology | [30, 64] |
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