De Martino Eleonora, Brunetti Davide, Canzonieri Vincenzo, Conforti Claudio, Eisendle Klaus, Mazzoleni Guido, Nobile Carla, Rao Federica, Zschocke Johannes, Jukic Emina, Jaschke Wolfram, Weinlich Georg, Zelger Bernhard, Schmuth Matthias, Stanta Giorgio, Zanconati Fabrizio, Zalaudek Iris, Bonin Serena
DSM-Department of Medical Sciences, University of Trieste, 34149 Trieste, Italy.
Pathology Unit, IRCCS CRO Aviano-National Cancer Institute, 33081 Aviano, Italy.
Cancers (Basel). 2020 Sep 29;12(10):2796. doi: 10.3390/cancers12102796.
Cutaneous melanoma (CM) incidence is rising worldwide and is the primary cause of death from skin disease in the Western world. Personal risk factors linked to environmental ultraviolet radiation (UVR) are well-known etiological factors contributing to its development. Nevertheless, UVR can contribute to the development of CM in different patterns and to varying degrees. The present study aimed at investigating whether altitude of residence can contribute to the development of specific types of CM and/or influence its progression. To this aim, 306 formalin-fixed and paraffin-embedded (FFPE) tissues from primary CM diagnosed in different geographical areas were submitted to B-RAF proto-oncogene serine/threonine kinase (BRAF) and N-RAS proto-oncogene GTPase (NRAS) mutational status detection and mRNA and miRNA profiling by qPCR. Genes were chosen for their functions in specific processes, such as immune response (, , or ) and pigmentation (, , and ). Furthermore, four microRNAs, namely , , , and , were included in the profiling. Our results highlight differences in the gene expression profile of primary CM with respect to the geographical area and the altitude of residence. Melanoma-specific survival was influenced by the gene expression of mRNA and miRNAs and varied with the altitude of patients' residence. In detail, and were highly expressed in patients living at higher altitudes, unlike , and . Since miRNAs are highly regulated by reactive oxygen species, it is possible that different regulatory mechanisms characterize CMs at different altitudes due to the different environment and UVR intensity.
皮肤黑色素瘤（CM）的发病率在全球范围内呈上升趋势，并且是西方世界皮肤疾病致死的主要原因。与环境紫外线辐射（UVR）相关的个人风险因素是导致其发生的众所周知的病因。然而，UVR 可通过不同模式和不同程度促进 CM 的发生。本研究旨在调查居住海拔是否会促进特定类型 CM 的发生和 / 或影响其进展。为此，对来自不同地理区域诊断的原发性 CM 的 306 份福尔马林固定石蜡包埋（FFPE）组织进行了 B-RAF 原癌基因丝氨酸 / 苏氨酸激酶（BRAF）和 N-RAS 原癌基因 GTP 酶（NRAS）突变状态检测以及通过 qPCR 进行 mRNA 和 miRNA 谱分析。选择这些基因是因其在特定过程中的功能，如免疫反应（ 、 或 ）和色素沉着（ 、 及 ）。此外，四个 microRNA，即 、 、 和 ，也包含在谱分析中。我们的结果突出了原发性 CM 的基因表达谱在地理区域和居住海拔方面的差异。黑色素瘤特异性生存率受 mRNA 和 miRNA 的基因表达影响，并随患者居住海拔而变化。具体而言， 和 在居住在较高海拔的患者中高表达，与 和 不同。由于 microRNA 受活性氧高度调控，由于不同的环境和 UVR 强度，不同海拔的 CM 可能具有不同的调控机制。
