Exosomal MicroRNA -142-5p in Serum is a Prognostic Factor in Cutaneous Squamous Cell Carcinoma

H. Han, Jong Yeup Kim, S. Jeon, J. Choi
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Abstract

Purpose: Exosomal microRNAs in tumor microenvironment can have a significant impact on the plasticity of cancer cells leading to the promotion of metastasis and angiogenesis. MicroRNAs expressed in tumor cells, fibroblasts, immune cells, and endothelial cells are known to target mRNAs in origin cells to promote tumor growth and metastasis, and induce changes in cell phenotype and expression and secretion of cytokines. MicroRNA expression patterns, which change depending on the tumor type, provide clues that can serve as a biological marker for diagnosis, determining the outcome of the disease, and treatment responses. However, there has been no definitive study on the relationship between exosomal microRNAs and prognosis in cutaneous squamous cell carcinoma. Here, we studied the association between prognosis of cutaneous squamous cell carcinoma patients and microRNAs detected in blood serum. Patients and methods: We enrolled 43 patients with various stages of cutaneous squamous cell carcinoma. Blood samples from patients were obtained and serum was separated by the using centrifuge. microRNAs were purified from serum exosomes, and microRNA sequencing was performed. The microRNA expression profiles and copy number variations of 43 serum samples were obtained using next-generation sequencing (Hiseq, Illumina). We analyzed the relationship between the microRNA changes and patient prognosis. Results: miR-142a-5p cluster expression levels in serum exosomes were most correlated with the poor prognosis of cutaneous squamous cell carcinoma. Exosomal miR-142-5p expression levels in serum were significantly higher (P< 0.01) in patients with late-stage disease than in those with early-stage disease. In addition, patients with recurrent tumors showed high levels of miR-142-5p. Conclusion: miR-142-5p expression level may be an essential marker for predicting patient prognosis and to help decide whether to undergo additional systemic chemotherapy after surgery. secretes exosomes containing miRNAs and transmits signals to their respective receiving cells. Our results show that the serum miRNA-142-5p cluster could be a potential biomarker for predicting the recurrence of cutaneous cell carcinoma. The TNM stage is typically already 3 or higher when lymphatic metastasis occurs. However, despite recurrence, no lymph node metastasis was observed at the time of diagnosis. An analysis of the serum external miRNA expression profile in this study showed that four serum exosomal miRNAs (miRNA-106a-3p, miRNA-10a-3p, miR-142-5p, miRNA-192a-5p) were adjusted to match cutaneous cell carcinoma progression. Among them, only miRNA-142-5p was found to be statistically related to overall survival. MiRNAs predictive ability
血清外泌体MicroRNA -142-5p是皮肤鳞状细胞癌的一个预后因素
目的:肿瘤微环境外泌体microrna对癌细胞的可塑性有显著影响,从而促进癌细胞转移和血管生成。已知在肿瘤细胞、成纤维细胞、免疫细胞和内皮细胞中表达的MicroRNAs可以靶向起源细胞中的mrna,促进肿瘤生长和转移,并诱导细胞表型和细胞因子表达和分泌的变化。MicroRNA表达模式的变化取决于肿瘤类型,它提供了线索,可以作为诊断的生物学标志物,决定疾病的结果和治疗反应。然而,在皮肤鳞状细胞癌中,外泌体microrna与预后之间的关系尚无明确的研究。在这里,我们研究了皮肤鳞状细胞癌患者的预后与血清中检测到的microrna的关系。患者和方法:我们招募了43例不同分期的皮肤鳞状细胞癌患者。取患者血样,离心分离血清。从血清外泌体中纯化microRNA,并进行microRNA测序。采用新一代测序(Hiseq, Illumina)获得43份血清样品的microRNA表达谱和拷贝数变化。我们分析了microRNA变化与患者预后的关系。结果:血清外泌体中miR-142a-5p簇表达水平与皮肤鳞状细胞癌预后不良最相关。晚期疾病患者血清外泌体miR-142-5p表达水平明显高于早期疾病患者(P< 0.01)。此外,复发肿瘤患者的miR-142-5p水平也较高。结论:miR-142-5p表达水平可能是预测患者预后的重要指标,有助于决定术后是否进行额外的全身化疗。分泌含有mirna的外泌体并将信号传递给各自的接收细胞。我们的研究结果表明,血清miRNA-142-5p簇可能是预测皮肤细胞癌复发的潜在生物标志物。当发生淋巴转移时,TNM期通常已经达到3或更高。然而,尽管复发,但在诊断时未观察到淋巴结转移。本研究中对血清外部miRNA表达谱的分析显示,四种血清外泌体miRNA (miRNA-106a-3p, miRNA-10a-3p, miR-142-5p, miRNA-192a-5p)被调整以匹配皮肤细胞癌的进展。其中,仅发现miRNA-142-5p与总生存率有统计学相关性。MiRNAs预测能力
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