肢端型黑色素瘤血浆外泌体miRNAs标志物的筛查及其在转移过程中的作用机制研究

肢端型黑色素瘤为有色人种最为常见的黑色素瘤类型，较其他皮肤部位的黑色素瘤预后更差。早期确诊及预测转移对于改善肢端型黑色素瘤患者的预后至关重要，而国际上有关肢端型黑色素瘤的研究进展缓慢，目前仍缺乏能有效辅助诊断、评估预后的分子指标。申请者成功建立起血浆及体外培养细胞上清中外泌体的分离及鉴定方法，并对3对肢端型黑色素瘤原发及转移配对血进行了外泌体miRNAs-seq检测，证实原发及转移患者中的血浆外泌体中miRNAs表达存在差异。在此基础上，拟进一步澄清肢端型黑色素瘤外周血中外泌体miRNAs的表达谱变化及与临床特点和预后的关系，探索外泌体miRNAs调控肢端型黑色素瘤进展的分子机制，以期寻找到有助于肢端型黑色素瘤的早期确诊及监测疾病进展的有效靶标。该项研究具有良好的临床应用前景，将有助于制定适合肢端型黑色素瘤患者的新型诊疗策略，为降低肢端型黑色素瘤的误诊率、延长患者的生存期提供助力。

Acral melanoma (AM) is the predominant melanoma subtype in non-Caucasians. Compared with common cutaneous melanoma, AM has a poorer prognosis. Early diagnosis and prediction of metastasis are critical for improving the prognosis of patients with AM. However, international research on AM has been restricted, and there is still a lack of potential biomarkers for diagnosis and prognosis. The applicant successfully established a method for isolation and identification of exosomes from plasma and supernatants of cell cultures in vitro. Exosomal miRNA profiling of three pairs of primary and metastatic blood samples from patients with AM was performed using miRNA-seq. On this basis, we aim to identify significant differentially expressed exosomal miRNAs in circulation system, and evaluate the power of individual and subsets of miRNAs to predict metastasis and outcome. Furthermore, we will explore the molecular mechanism of exosomal miRNAs in regulating the progression of AM, and to find effective targets for early diagnosis and monitoring of disease progression of AM. This study has a good prospect for clinical application, will contribute to develop a new diagnosis strategy for patients with AM, to decrease misdiagnosis rates and prolong the survival of patients.