Prognostic and Clinicopathological Significance of CCND1/Cyclin D1 Upregulation in Melanomas: A Systematic Review and Comprehensive Meta-Analysis

Abstract

Our objective was to evaluate the prognostic and clinicopathological significance of cyclin D1 (CD1) overexpression/CCND1 amplification in melanomas. We searched studies published before September 2019 (PubMed, Embase, Web of Science, Scopus). We evaluated the quality of the studies included (QUIPS tool). The impact of CD1 overexpression/CCND1 amplification on overall survival and relevant clinicopathological characteristic were meta-analyzed. We performed heterogeneity, sensitivity, small-study effects, and subgroup analyses. Forty-one studies and 3451 patients met inclusion criteria. Qualitative evaluation demonstrated that not all studies were performed with the same rigor, finding the greatest risk of bias in the study confounding domain. Quantitative evaluation showed that immunohistochemical CD1 overexpression had a statistical association with Breslow thickness (p = 0.007; OR = 2.09,95% CI = 1.23–3.57), significantly higher frequency of CCND1/cyclin D1 abnormalities has been observed in the primary tumor compared to distant metastases (p = 0.004), revealed also by immunohistochemical overexpression of the protein (p < 0.001; OR = 0.53,95% CI = 0.40–0.71), while the CCND1 gene amplification does not show association (p = 0.43); while gene amplification, on the contrary, appeared more frequently in distant metastases (p = 0.04; OR = 1.70,95% CI = 1.01–2.85) and not in the primary tumor. In conclusion, CCND1/cyclin D1 upregulation is a common molecular oncogenic alteration in melanomas that probably favors the growth and expansion of the primary tumor. This upregulation is mainly consequence to the overexpression of the cyclin D1 protein, and not to gene amplification.

Hallmarks of Cancer Applied to Oral and Oropharyngeal Carcinogenesis: A Scoping Review of the Evidence Gaps Found in Published Systematic Reviews

“…In melanoma, the MAPK pathway can also be activated by mutations in BRaf (BRafv600E), while the PI3K pathway can be constitutively activated by mutations in its PI3K component. As will be seen below, both pathways mediate their proliferation-stimulating activity essentially through upregulation by translational activation of the CCND1 gene encoding the cyclin D1 (CD1) protein [ 109 , 110 ] ( Figure 3 a).…”

DNA damage and NF‐κB inactivation implicate glycyrrhizic acid‐induced G 1 phase arrest in hepatocellular carcinoma cells

“…Cyclin D1, encoded by the CCND1 gene, is a cell cycle regulator that mediates cell cycle progression through promoting G 1 /S phase transition (González‐Ruiz et al, 2021). NF‐κB, the p50/p65 heterodimer of transcription factor, may induce CCND1 expression and lead to the upregulation of Cyclin D1 (Hartman et al, 2020; Velho et al, 2012).…”

Hallmarks of Cancer Expression in Oral Lichen Planus: A Scoping Review of Systematic Reviews and Meta-Analyses

“…The activation of the pro-proliferative MAPK and PI3K/Akt pathways can also occur through the stimulation of Ras protein and its downstream targets [ 64 ]. The Ras oncogene is frequently mutated in human melanomas [ 84 , 85 ] and is one of the most frequently altered oncogenes in OSCC [ 86 ], especially with regard to HRas mutations [ 87 , 88 ], leading to its constitutive activation with hyperproliferation. It should be noted that, despite the importance of this pathway in oral carcinogenesis, there are no primary-level studies and therefore no systematic reviews or meta-analyses that provide information on OLP.…”