Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
J Invest Dermatol. 2010 Aug;130(8):2062-70. doi: 10.1038/jid.2010.63. Epub 2010 Apr 1.
Malignant cutaneous melanoma is a highly aggressive form of skin cancer. Despite improvements in early melanoma diagnosis, the 5-year survival rate remains low in advanced disease. Therefore, novel biomarkers are urgently needed to devise new means of detection and treatment. In this study, we aimed to improve our understanding of microRNA (miRNA) deregulation in melanoma development and their impact on patient survival. Global miRNA expression profiles of a set of melanoma lymph node metastases, melanoma cell lines, and melanocyte cultures were determined using Agilent array. Deregulated miRNAs were evaluated in relation with clinical characteristics, patient survival, and mutational status for BRAF and NRAS. Several miRNAs were differentially expressed between melanocytes and melanomas as well as melanoma cell lines. In melanomas, miR-193a, miR-338, and miR-565 were underexpressed in cases with a BRAF mutation. Furthermore, low expression of miR-191 and high expression of miR-193b were associated with poor melanoma-specific survival. In conclusion, our findings show miRNA dysregulation in malignant melanoma and its relation to established molecular backgrounds of BRAF and NRAS oncogenic mutations. The identification of an miRNA classifier for poor survival may lead to the development of miRNA detection as a complementary prognostic tool in clinical practice.
恶性皮肤黑色素瘤是一种高度侵袭性的皮肤癌。尽管早期黑色素瘤的诊断有所改善,但晚期疾病的 5 年生存率仍然较低。因此,迫切需要新的生物标志物来设计新的检测和治疗方法。在这项研究中,我们旨在提高对黑色素瘤发展过程中 miRNA 失调及其对患者生存影响的认识。使用 Agilent 阵列测定了一组黑色素瘤淋巴结转移、黑色素瘤细胞系和黑素细胞培养物的全局 miRNA 表达谱。评估了失调 miRNA 与临床特征、患者生存和 BRAF 和 NRAS 突变状态的关系。黑素细胞和黑色素瘤以及黑色素瘤细胞系之间存在几种 miRNA 的差异表达。在黑色素瘤中,miR-193a、miR-338 和 miR-565 在 BRAF 突变病例中表达下调。此外,miR-191 表达降低和 miR-193b 表达升高与黑色素瘤特异性生存不良相关。总之,我们的研究结果表明恶性黑色素瘤存在 miRNA 失调,并且与 BRAF 和 NRAS 致癌突变的既定分子背景有关。识别用于不良生存的 miRNA 分类器可能会导致 miRNA 检测作为临床实践中补充预后工具的发展。
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