Table 2.

Main biomarkers associated with the relationship between OSA and cancer.

Biomarker	Main Functions	Biomarker in OSA and Cancer
HIF-1α [87]	Inducer of angiogenic processes.	Inducer of angiogenic processes. Increased levels associated with aggressiveness of melanoma in patients with OSA.
VEGF [89]	Promoter of tumor growth and metastasis. Inducer of angiogenic processes.	No specific relationship between circulating levels with variables of OSA severity. Inconsistency between VEGF levels and malignancy of the tumor in OSA. Future studies must elucidate the consequences of intermittent hypoxia associated with OSA in the expression of HIF-1α and VEGF at the tumor level.
VCAM-1 [94]	Marker associated with tumor aggressiveness. Specific functions in tumor growth, formation of metastatic niches, and angiogenic process.	Increased levels of VCAM-1 in patients with OSA and melanoma.
PD-1/PD-L1 [33,84]	Complex that participates in different cancer stages. Used as immune checkpoint blockade therapies in cancer treatment.	The biomarker HIF-1α has a regulatory function in PD-1/PD-L1 expression in patients with severe OSA. Increased levels of the soluble part of PD-L1 (sPD-L1) in patients with OSA and melanoma. Potential utility as biomarker for the characterization of aggressiveness and metastasis in melanoma.
TGF-β [95]	Common expression in the tumor microenvironment. A major pleiotropic role in cancer.	In OSA patients with cutaneous melanoma, TGF-β1 levels correlated with melanoma aggressiveness, but only in patients without obesity. HIF1α-mediated induction of TGF-β appears to play a key role in establishing an immunosuppressive phenotype in monocytes and natural killer cells of patients with OSA. Basic models of hypoxia and hypoxic ischemic tissues reported increased levels of this biomarker.
PSPC1 [11]	Nuclear bodies are located in the interchromatin space of the cell nucleus. Paraspeckle formation carry on numerous cell stress scenarios such as malignant transformation.	Intermittent hypoxia mediates PSPC1 upregulation in OSA. PSPC1 protein expression would be accompanied by increased levels of TGFβ, resulting in a tumor progression function.
TNF-α [101]	A pro-inflammatory molecule with a role in systemic inflammatory response. Increased plasma concentration is associated with cardiovascular outcomes.	TNF-α plays a role in the control of tumor growth. Elevated TNF-α levels in adults are correlated with severity of OSA. Further research is needed to explore the potential association between increased TNF-a and tumor progression in patients with OSA and cancer.
COX-2/PGE2 [71]	Cyclooxygenase pathway (COX-1/COX-2) results in production of PGE2. PGE2 plays a central role in the regulation of multiple biological processes under normal and pathological conditions. COX-2 has been identified in many human cancers, precancerous lesion, and metastasis.	Intermittent hypoxia induces expression of COX-2, resulting in an increased synthesis of PGE2. A new hypothesis indicates that up-regulation of the COX-2/PGE2 pathway induced by hypoxia would play a central role in the association of OSA and cancer.
Cannabinoid receptors [103]	Biomarkers associated with tumor progression. Specific subtypes of cannabinoid receptors (CBs) participate in several physiological processes.	CB agonists promote proliferation and aggressiveness of colon cancer cells through the activation of AKT/GSK-3β pathway. Chronic intermittent hypoxia facilitates proliferation and migration of breast cancer cells by upregulating CB1 and CB2 in vitro and in vivo.
Endostatin [104]	Potent inhibitor of tumor angiogenesis, endothelial proliferation, and tumor growth. Potential therapeutic role in cancer.	Intermittent hypoxia promotes tumor growth and cancer progression in mice models. Anti-tumor effect of endostatin in animal models under intermittent hypoxia (OSA model).
Endothelin-1 [28]	Promoter of cell proliferation and migration, angiogenesis, metastasis, and chemoresistance.	Cancer promotion role of endothelin-1 and its receptors under intermittent hypoxia conditions. In in vitro and in vivo models, endothelin receptor blockade prevents intermittent hypoxia-induced tumor development.