Table 3.

Predictive biomarkers.

References	Cancer Type	Biomarker Name-Gene	Function	Sample Type	Biomarker Behavior	Application
[38]	HNSCC	PDCD1 (PD-1)	The PD1/PD-L1 axis is implicated in the downregulation of immune responses in tumors, affecting T-cell responses in secondary lymphoid tissues, moving the balance from T-cell activation to antigen tolerance.	Tissue	Mpdcd1 → response to immunotherapies targeting the PD-1/PD-L1 axis.	Prediction
[42]	HNSCC	IDO1	Encodes indoleamine 2,3-dioxygenase (IDO)—an enzyme that limits the rate of conversion of the crucial amino acid tryptophan to kynurenine, it is strongly expressed in many types of tumors and has been shown to play a role in the immunosuppression of naïve cells through increased tryptophan metabolism in the tumor microenvironment (TME). Increased expression of IDO1 can result in suppression of anti-tumor T-cells, differentiation of CD4+ T-cells into immunosuppressive regulatory T-cells (Tregs), and polarization of anti-gene cells into a tolerogenic phenotype.	Tissue	Response to IDO1 immune checkpoint inhibitors.	Prediction
[50]	HNSCC	OX40 (TNFRSF4)	Encodes tumor necrosis factor receptor, which is primarily expressed on the surface of activated T cells and is stimulated by its receptor OX40L, which is located on antigenic cells, activated T cells, lymphoid tissue inductor cells, certain endothelial cells, and mast cells. Its regulation induces differentiation, proliferation, and extended survival of T cell-activated cells through inhibition of activation-induced cell death, as well as stimulation of cytokine synthesis.	Tissue	Identifying HNSCC patients who would benefit from adjuvant immunotherapy.	Prediction
[50]	HNSCC	GITR (TNFRSF18, AITR)	Encodes the tumor necrosis factor receptor, is highly expressed by regulatory T cells (Tregs) and expressed at lower levels on naïve, effector, and memory T cells. Binding of the GITR ligand in combination with T cell receptor stimulation causes activation of the MAPK/ERK and NFkB pathway, resulting in immune system upregulation with T cell proliferation, production of proinflammatory cytokines, enhanced anti-cancer effector function, and resistance of CD4+ and CD8+ T cells. GITR promotes anti-cancer immunity by enhancing effector T cell function and by suppressing Treg proliferation.	Tissue	Identifying HNSCC patients who would benefit from adjuvant immunotherapy.	Prediction
[76]	HNSCC	DAPK	Encodes calcium/calmodulin (CaM)-regulated serine/threonine protein kinase, has pro-apoptotic function, mediates cell death triggered by a variety of death-inducers, including interferon-γ, 20 TGF, 21 TNFα, and Fas ligand.	Cell lines	Hypermethylation -low expression → resistance to cetuximab and erlotinib.	Prediction
[77]	HNSCC	DNA methylation	ILK signaling, glucocorticoid receptor signaling, fatty acid α-oxidation, cell cycle regulation.	Cell lines	Hypermethylation → radiation resistance.	Prediction
[78]	HNSCC	ZFG36 gene -TTP	Tumor-suppressor, encodes Arna-binding protein, enhances decay of AU-rich element (ARE)-containing transcripts, and plays an important role in cellular differentiation, proliferation, tumorigenesis, and immunity, modulates the posttranscriptional control of inflammatory mediators, and immune gene expression.	Cell lines	Hypermethylation-low expression → overexpression of CD47 in a radioresistant cell line (HN31R) → inhibition of phagocytosis. Prediction of the efficacy of CD47 antibody in recurrent HNSCC patients after radiotherapy.	Prediction
[79]	HNSCC	Gene panel (CRIP1, G0S2, MLH1, OPN3, S100 and TUBB2A)	CRIP1: Cysteine Rich Protein 1 G0S2: G0/G1 switch gene 2 Mlh1: MutL protein homolog 1 OPN3: Opsin 3 S100 TUBB2A: Tubulin Beta 2A Class Iia	Tissue	Hypermethylation → cisplatin-resistance.	Prediction
[80]	HNSCC	PTPRT	A member of the PTPR family, receptor of PTPs (enzymes that catalyze the removal of a phosphate group from specific signaling proteins), they cover the membrane once and contain one or two intracellular catalytic sites, as well as a modular extracellular region that typically contains several protein-protein interaction sites.	Tissue	Hypermethylation → sensitivity to STAT3 targeting agents.	Prediction
[81]	HNSCC	DNA methylation profile	Genes involved in different molecular pathways, namely Axon guidance, Hippo signaling, Pathways in cancer and MAPK signaling	Tissue	Both hypermethylation and hypomethylation → predict response to ICI.	Prediction
[82]	LA-HNSCC	DUSP2	Encodes a nuclear phosphatase that is strongly expressed in activated immune cells and catalyzes the dephosphorylation of serine, threonine, and tyrosine residues on various types of mitogen-activated protein kinases inside MAPK TXY.	Tissue	Patients treated with CRT: Low EGFR + unmethylated DUSP2 → longer overall survival Compared to low EGFR + meth-DUSP2 Unmethylated DUSP2 + Mtp53 → longer survival compared to unmethylated DUSP2 + wtTP53. Methylated DUSP2 + high EGFR, + wild type TP53 → highest OS and HR.	Prediction
[83]	HNSCC	CCND1	Encodes a regulator of the G1/S phase transition, it is degraded as the cell enters the S phase.	Tissue	Response to selective FGFR1/3 inhibitors PD 173074 and AZD4547.	Prediction
[83]	HNSCC	FGFR2	Encodes a fibroblast growth factor receptor.	Tissue	Response to selective FGFR1/3 inhibitors PD 173074 and AZD4547.	Prediction
[83]	HNSCC	FGF5	Encodes a cell signaling protein.	Tissue	Response to selective FGFR1/3 inhibitors PD 173074 and AZD4547.	Prediction