Background: Cutaneous melanoma (CM) is one of the most lethal tumors among skin cancers and its incidence is rising worldwide. Recent data support the role of microRNAs (miRNAs) in melanoma carcinogenesis and their potential use as disease biomarkers. Methods: We quantified the expression of miR-146a-5p and miR-21-5p in 170 formalin-fixed paraffin embedded (FFPE) samples of CM, namely 116 superficial spreading melanoma (SSM), 26 nodular melanoma (NM), and 28 lentigo maligna melanoma (LMM). We correlated miRNA expression with specific histopathologic features including Breslow thickness (BT), histological subtype, ulceration and regression status, and mitotic index. Results: miR-146a-5p and miR-21-5p were significantly higher in NM compared to SSM and LMM. The positive correlation between miR-146a-5p and miR-21-5p expression and BT was confirmed for both miRNAs in SSM. Considering the ulceration status, we assessed that individual miR-21-5p expression was significantly higher in ulcerated CMs. The increased combined expression of the two miRNAs was strongly associated with ulceration (p= 0.0093) and higher mitotic rate (≥1/mm2) (p= 0.0005). We demonstrated that the combination of two-miRNA expression and prognostic features (BT and ulceration) can better differentiate cutaneous melanoma prognostic groups, considering overall survival and time-to-relapse clinical outcomes. Specifically, miRNA expression can further stratify prognostic groups among patients with BT ≥ 0.8 mm but without ulceration. Our findings provide further insights into the characterization of CM with specific prognostic features. The graphical abstract was created with BioRender.com.
背景：皮肤黑色素瘤（CM）是皮肤癌中最具致死性的肿瘤之一，其全球发病率持续上升。最新研究数据支持微小RNA（miRNAs）在黑色素瘤发生发展中的作用及其作为疾病生物标志物的潜在价值。 方法：我们对170例福尔马林固定石蜡包埋（FFPE）的CM样本（包括116例浅表扩散型黑色素瘤[SSM]、26例结节型黑色素瘤[NM]和28例恶性雀斑样痣黑色素瘤[LMM]）中miR-146a-5p和miR-21-5p的表达水平进行定量分析，并将miRNA表达与Breslow厚度（BT）、组织学亚型、溃疡与退行状态、有丝分裂指数等特定病理特征进行关联性研究。 结果：与SSM和LMM相比，NM中miR-146a-5p和miR-21-5p表达水平显著升高。在SSM中，两种miRNA的表达均与BT呈显著正相关。针对溃疡状态的分析显示，miR-21-5p在溃疡型CM中表达显著升高。两种miRNA的联合高表达与溃疡状态（p=0.0093）及较高有丝分裂率（≥1/mm²）（p=0.0005）密切相关。研究证实，结合双miRNA表达与预后特征（BT和溃疡状态）能更有效区分CM患者的预后分组，这一结论基于总生存期和复发时间的临床结局分析。特别值得注意的是，在BT≥0.8 mm但无溃疡的患者中，miRNA表达可进一步实现预后亚组分层。本研究为具有特定预后特征的CM提供了新的生物学见解。图形摘要通过BioRender.com制作。
Association of miR-146a-5p and miR-21-5p with Prognostic Features in Melanomas
肿瘤(癌症)患者之家