Fawzy Manal S, Ibrahiem Afaf T, Bayomy Naglaa A, Makhdoom Amin K, Alanazi Khalid S, Alanazi Abdulaziz M, Mukhlef Abdulaziz M, Toraih Eman A
Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar 91431, Saudi Arabia.
Department of Pathology, Faculty of Medicine, Northern Border University, Arar 91431, Saudi Arabia.
Diagnostics (Basel). 2023 Mar 22;13(6):1205. doi: 10.3390/diagnostics13061205.
Cutaneous melanoma is a severe and life-threatening form of skin cancer with growing incidences. While novel interventions have improved prognoses for these patients, early diagnosis of targeted treatment remains the most effective approach. MicroRNAs have grown to good use as potential biomarkers for early detection and as targets for treatment. miR-155 is well-studied for its role in tumor cell survival and proliferation in various tissues, although its role in melanoma remains controversial. In silico data analysis was performed in the dbDEMC v.3 to identify differentially expressed miRNA. We validated gene targets in melanoma using TarBase v8.0 and miRPath v3.0 and determined protein-protein interactions of the target genes. One hundred forty patients (age range 21-90 years) with cutaneous melanoma who underwent resection were included. Molecular assessment using Real-Time RT-qPCR, clinicopathological associations, and a literature review for the different roles of miR-155 in melanoma were performed. Analysis of the dbDEMC reveals controversial findings. While there is evidence of upregulation of miR-155 in primary and metastatic melanoma samples, others suggest decreased expression in later-stage melanoma and cases with brain metastasis. miR-155 has been overexpressed in prior cases of melanoma and precancerous lesions, and it was found to be dysregulated when compared to benign nevi. While miR-155 expression was associated with favorable outcomes in some studies, others showed an association with metastasis. Patients with high levels of miR-155 also noted reduction after receiving anti-PD-1 treatment, correlated with more prolonged overall survival. In our patient's cohort, 22.9% relapsed during treatment, and 45% developed recurrence, associated with factors such as lymph node infiltration, high mitotic index, and positive staining for CD117. Although overall analysis revealed miR-155 downregulation in melanoma specimens compared to non-cancer tissues, increased expression of miR-155 was associated with cases of superficial spreading melanoma subtype ( = 0.005) and any melanoma with a high mitotic rate ( = 0.010). The analysis did not identify optimum cutoff values to predict relapse, recurrence, or mortality. In conclusion, miR-155 could have, in part, a potential prognostic utility in cutaneous melanoma. Further mechanistic studies are required to unravel the multifunctional role of miR-155 in melanoma.
皮肤黑色素瘤是一种严重且危及生命的皮肤癌,其发病率呈上升趋势。虽然新型干预措施改善了这些患者的预后,但早期诊断并进行靶向治疗仍然是最有效的方法。微小RNA已成为早期检测的潜在生物标志物和治疗靶点。miR-155因其在各种组织中的肿瘤细胞存活和增殖中的作用而得到充分研究,尽管其在黑色素瘤中的作用仍存在争议。在dbDEMC v.3中进行了计算机数据分析,以识别差异表达的微小RNA。我们使用TarBase v8.0和miRPath v3.0验证了黑色素瘤中的基因靶点,并确定了靶基因的蛋白质-蛋白质相互作用。纳入了140例接受切除手术的皮肤黑色素瘤患者(年龄范围21 - 90岁)。使用实时RT-qPCR进行分子评估、临床病理关联分析,并对miR-155在黑色素瘤中的不同作用进行文献综述。对dbDEMC的分析揭示了有争议的结果。虽然有证据表明原发性和转移性黑色素瘤样本中miR-155上调,但也有研究表明晚期黑色素瘤和脑转移病例中miR-155表达降低。miR-155在先前的黑色素瘤和癌前病变病例中过表达,与良性痣相比,发现其表达失调。虽然在一些研究中miR-155表达与良好预后相关,但其他研究表明其与转移相关。miR-155水平高的患者在接受抗PD-1治疗后也出现降低,这与更长的总生存期相关。在我们的患者队列中,22.9%在治疗期间复发,45%出现复发,与淋巴结浸润、高有丝分裂指数和CD117阳性染色等因素相关。尽管总体分析显示与非癌组织相比,黑色素瘤标本中miR-155下调,但miR-155表达增加与浅表扩散型黑色素瘤亚型病例(= 0.005)和任何有高有丝分裂率的黑色素瘤相关(= 0.010)。该分析未确定预测复发、复发或死亡率的最佳临界值。总之,miR-155在皮肤黑色素瘤中可能具有部分潜在的预后价值。需要进一步的机制研究来阐明miR-155在黑色素瘤中的多功能作用。