目的:利用生物信息学方法分析与葡萄膜恶性黑色素瘤转移相关的非编码RNA,以及它们作为竞争性内源RNA的作用机制。方法:从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库下载80例葡萄膜恶性黑色素瘤患者的RNA测序数据和临床资料,采用edgeR算法分析转移与非转移患者组织中差异表达(differentially expressed,DE)的长链非编码RNA(lncRNA)、微小RNA(miR)和mRNA,并构建lncRNA-miR-mRNA的竞争性内源RNA(competing endogenous RNA,ceRNA)调控网络,基因富集分析和通路分析研究网络中mRNA的生物学功能。Kaplan-Meier生存曲线分析ceRNA网络中核心RNA与生存率的关系。结果:从发生远处转移的葡萄膜恶性黑色素瘤样本中,共鉴定出346个上调的mRNA,118个下调的miR和45个上调的lncRNA。其中67个mRNA,7个miR和30个lncRNA相互组合形成616个ceRNA单元,并形成了一个具有181条边线ceRNA网络。基因富集分析表明:网络中的mRNA富集在肿瘤生成和转移相关的几个基因本体(Gene Ontology)和信号通路。拓扑分析确定了6个核心lncRNA(LINC00861、LINC02421、BHLHE40-AS1、LINC01252、LINC00513和LINC02389)和3个核心mRNA(UNC5D、BCL11B和MTDH)。 所有核心lncRNA、核心mRNA的表达水平和5个miR(miR-221、miR-222、miR-506、miR-507、miR-876)的表达水平均与总体生存率显着相关(均P<0.05)。结论:本研究揭示了几种lncRNA及其相关的ceRNA网络在葡萄膜恶性黑色素瘤转移中的作用,为进一步研究葡萄膜恶性黑色素瘤的发生和/或转移提供了新的方向。
Objective: To elucidate the expression of long non-coding RNAs (lncRNAs) and their roles as competing endogenous RNAs (ceRNAs) in uveal melanoma (UM) metastasis. Methods: RNA sequencing data and clinical information of 80 patients with UM were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed (DE) mRNAs, microRNAs (miR), and lncRNAs between metastatic and non-metastatic individuals with UM were screened using the edgeR algorithm. Gene enrichment analysis was conducted for the DE mRNAs. LncRNA-miR-mRNA regulatory triples and a ceRNA network were constructed. Betweenness centrality was used to screen hub genes and lncRNAs for subnetwork analysis. Kaplan-Meier survival analysis was conducted to explore correlations between the expression of hub RNAs and overall survival in the TCGA UM cohort. Results: A total of 346 upregulated mRNAs, 118 downregulated miRs, and 45 upregulated lncRNAs were identified in samples with systemic metastasis. Among them, 67 mRNAs, 7 miRs, and 30 lncRNAs mapped to 616 ceRNA triples, thus forming an interconnected ceRNA network with 181 edges. Gene enrichment analysis revealed that mRNAs in the network were enriched in multiple gene ontology terms and pathways associated with carcinogenesis and metastasis. Topological analysis identified 6 hub lncRNAs (LINC00861, LINC02421, BHLHE40-AS1, LINC01252, LINC00513, and LINC02389) and 3 hub mRNAs (UNC5D, BCL11B, and MTDH). The expression levels of all hub genes and 5 DEmiRs (miR-221, miR-222, miR-506, miR-507, miR-876) were significantly associated with the overall survival probability. Conclusion: This bioinformatic study revealed the functions of several lncRNAs and their associated ceRNA network in UM metastasis. It provides a novel in silicon evidence for future experimental study on the pathogenesis of systemic metastasis in uveal melanoma, especially from the perspective of non-coding RNA.
前段巨眼(anterior megalophthalmos, AM)是一种罕见的双侧非进展性先天性眼前段增大疾病,表现为大角膜(直径≥ 12.5 mm)、前房极深、角膜厚度正常或轻中度变薄和睫状环扩大等。并发性白内障以及晶状体脱位是导致AM视力下降的主要原因。然而,解剖结构的异常使AM白内障手术具有很大的挑战性。文章报道了一例AM合并白内障的48岁男性患者,成功为其行手法小切口白内障摘除联合人工晶状体(intraocular lens, IOL)一期植入术,患者术后视力恢复良好,IOL位置居中,未出现较大的屈光误差。对该典型AM病例的临床特点以及手术难点的回顾总结,有助于加深广大眼科临床工作者对该疾病的认识。
Anterior megalophthalmos is a rare congenital enlargement of the anterior segment, characterized by bilateral nonprogressive megalocornea (diameter ≥12.5 mm), extremely deep anterior chamber, normal or moderate thinning of the cornea, and elongation of the ciliary ring. Cataract and lens dislocation are the main causes of decreased vision in patients with AM. However, cataract surgery on patients with AM are challenging due to the anatomical abnormalities. This case reports a 48-year-old male patient diagnosed with AM and cataract, who successfully underwent a manual small incision cataract extraction combined with intraocular lens implantation. Finally, our patient showed a good visual outcome with a well centered IOL and without obvious refractive error. In this typical AM case, we reviewed and summarized the clinical characteristics and the challenges of surgical treatment so that other ophthalmologists can learn about this disease.
前段巨眼(anterior megalophthalmos, AM)是一种罕见的双侧非进展性先天性眼前段扩大疾病,表现为大角膜、角膜厚度正常或轻中度变薄、前房明显加深、睫状环扩大和悬韧带松弛。早期症状可仅表现为角膜散光和屈光不正等,并发性白内障和晶状体脱位是AM患者视力下降的主要原因。眼前段解剖结构的异常使AM患者的白内障手术具有很大的挑战性。首先,极端前房深度引起的有效晶状体位置(ELP)预测误差及公式选择不当是导致其术后较大屈光误差的主要原因;其次,悬韧带松弛易导致晶状体脱位、后囊膜破裂和玻璃体脱出等术中并发症的发生;由于超大囊袋及悬韧带松弛,人工晶状体(IOL)偏心甚至脱位也是术后常见的并发症。因此,需根据患者悬韧带情况、晶状体混浊程度采取合适的手术方式及谨慎选择IOL的类型。采用手法小切口晶状体囊外摘除术,可避免超声乳化的高灌注压对悬韧带的进一步损伤,增加手术的安全性;植入光学面及襻宽大的IOL术后具有较好的稳定性;新公式如Barrett Universal Ⅱ、Kane和EVO等公式具有较好的屈光预测准确性。然而,目前关于AM患者的白内障手术治疗报道仍属于个案报道,未来还需要更大样本量的临床研究进一步证实。
前段巨眼(anterior megalophthalmos, AM)是一种罕见的双侧非进展性先天性眼前段扩大疾病,表现为大角膜、角膜厚度正常或轻中度变薄、前房明显加深、睫状环扩大和悬韧带松弛。早期症状可仅表现为角膜散光和屈光不正等,并发性白内障和晶状体脱位是AM患者视力下降的主要原因。眼前段解剖结构的异常使AM患者的白内障手术具有很大的挑战性。首先,极端前房深度引起的有效晶状体位置(ELP)预测误差及公式选择不当是导致其术后较大屈光误差的主要原因;其次,悬韧带松弛易导致晶状体脱位、后囊膜破裂和玻璃体脱出等术中并发症的发生;由于超大囊袋及悬韧带松弛,人工晶状体(IOL)偏心甚至脱位也是术后常见的并发症。因此,需根据患者悬韧带情况、晶状体混浊程度采取合适的手术方式及谨慎选择IOL的类型。采用手法小切口晶状体囊外摘除术,可避免超声乳化的高灌注压对悬韧带的进一步损伤,增加手术的安全性;植入光学面及襻宽大的IOL术后具有较好的稳定性;新公式如Barrett Universal Ⅱ、Kane和EVO等公式具有较好的屈光预测准确性。然而,目前关于AM患者的白内障手术治疗报道仍属于个案报道,未来还需要更大样本量的临床研究进一步证实。