A prospective multicenter cohort study of cutaneous melanoma: clinical staging and potential associations with HIF-1α and VEGF expressions

Abstract

Melanoma is a highly prevalent cancer that is associated with substantial mortality. Although clinical staging procedures can serve as relatively robust prognostic indicators, we aimed to determine whether assessments of the abundance of hypoxia inducible factor-1α (HIF-1α) or vascular endothelial growth factor (VEGF) in postexcisional melanoma tumor tissues may enable more accurate determination of tumor aggressiveness. We carried out a multicenter prospective study, in which we systematically evaluated 376 consecutive patients diagnosed with melanoma, and performed histochemical assessments for both HIF-1α and VEGF immunoreactivity in the tumor biopsies. Multivariate analyses showed that higher HIF-1α expression, but not high VEGF, were associated significantly and independently with increased tumor aggressiveness as derived from several well-established aggressiveness criteria. A limitation of this study was that this was a descriptive prospective study lacking a post-hoc verification arm. Thus, the presence of increased numbers of positively labeled HIF-1α cells in melanoma tumors may potentially serve as an indicator of tumor phenotype and prognosis, and accordingly guide therapy.

Age‐dependent hypoxia‐induced PD‐L1 upregulation in patients with obstructive sleep apnoea

“…This finding could have clinically relevant consequences, as PD‐L1/PD‐1 crosstalk has a recognized role in the development and progression of cancer of any origin . Therefore, our results could provide biological plausibility to previous reports of increased risk of cancer incidence or mortality in young patients with OSA, which disappears in older patients . Moreover, it might be argued that the concordance between this biological finding and the mentioned clinical‐epidemiological data reinforces the potential role of the PD‐L1/PD‐1 pathway in the OSA–cancer relationship.…”

“…Indeed, several clinical and epidemiological studies suggest that the association between OSA and cancer incidence or cancer mortality is particularly prominent in younger rather than in older patients . Specifically, a recent prospective clinical cohort study performed in our setting has shown that the independent association between OSA severity and cancer aggressiveness is particularly prominent among patients of <56 years of age . Moreover, a murine model of OSA has recently demonstrated that IH potentiates tumour progression through changes in the immune system in young mice, whereas such changes are not present in aged mice …”

HIF‐1α/VEGF signaling‐mediated epithelial–mesenchymal transition and angiogenesis is critically involved in anti‐metastasis effect of luteolin in melanoma cells

“…Tumor angiogenesis is another physiological process essentially required for tumor progression and metastasis (Shi, Chen, Wang, Guo, & Wang, 2018). Although increasing evidence indicates that angiogenesis is a highly sophisticated and coordinated process, the activation of a hypoxic-induced factor (HIF) growth factor pathway remains the key modulator (Martinez-Garcia et al, 2017). Tumor tissue is usually accompanied by hypoxia, which promotes HIF production.…”

Obstructive sleep apnea and comorbidities: a dangerous liaison

“…Tumor aggressiveness was increased in CMM patients with OSA and long time spent at low oxygen saturation (CT90%) or high oxygen desaturation index (ODI 4%) [158, 170–173]. Interestingly, tumor aggressiveness was positively associated with expression of the adhesion molecule VCAM-1 [171], HIF-1alpha [173], but not with expression of vascular endothelial growth factor (VEGF) [173]. Similar results were reported in patients with lung cancer and OSA [158].…”