- 作者列表："Xue D","Cheng P","Jiang J","Ren Y","Wu D","Chen W
:BACKGROUND Alternative splicing (AS), the mechanism underlying the occurrence of protein diversity, may result in cancer genesis and development when it becomes out of control, as suggested by a growing number of studies. However, systemically analyze of AS events at the genome-wide level for skin cutaneous melanoma (SKCM) is still in a preliminary phase. This study aimed to systemically analyze the bioinformatics of the AS events at a genome-wide level using The Cancer Genome Atlas (TCGA) SKCM data. MATERIAL AND METHODS The SpliceSeq tool was used to analyze the AS profiles for SKCM clinical specimens from the TCGA database. The association between AS events and overall survival was analyzed by Cox regression analysis. AS event intersections and a gene interaction network were established by UpSet plot. A multivariate survival model was used to establish a feature genes prognosis model. RESULTS A total of 103 SKCM patients with full clinical parameters available were included in this study. We established an AS network that investigated the relationship between AS events and clinical prognosis information. Furthermore, 4 underlying feature genes of SKCM (MCF2L, HARS, TFR2, and RALGPS1) were found in the AS network. We performed function analysis as well as correlation analysis of AS events with gene expression. Using the multivariate survival model, we further confirmed the 4 genes that impacted the classifying SKCM prognosis at the level of AS events as well as gene expression, especially in wild-type SKCM. CONCLUSIONS AS events could be ideal indicators for SKCM prognosis. The key feature gene MCF2L played an important role in wild-type SKCM.
背景选择性剪接 (AS) 是蛋白质多样性发生的潜在机制，如越来越多的研究表明，当它失去控制时，可能导致癌症的发生和发展。然而，在皮肤皮肤黑色素瘤 (SKCM) 的全基因组水平上系统分析AS事件仍处于初步阶段。本研究旨在利用癌症基因组图谱 (TCGA) SKCM数据在全基因组水平系统分析AS事件的生物信息学。材料和方法使用SpliceSeq工具分析TCGA数据库中SKCM临床标本的AS图谱。通过Cox回归分析AS事件与总生存率之间的相关性。作为事件交叉点和基因相互作用网络，通过打乱图建立起来。采用多变量生存模型建立特征基因预后模型。结果本研究共纳入 103 例具有完整临床参数的SKCM患者。我们建立了一个AS网络，研究AS事件与临床预后信息之间的关系。此外，在AS网络中发现了SKCM的 4 个潜在特征基因 (MCF2L、HARS、TFR2 和RALGPS1)。我们进行了功能分析以及as事件与基因表达的相关性分析。使用多变量生存模型，我们进一步证实了在AS事件水平以及基因表达水平上影响分类SKCM预后的 4 个基因，尤其是在野生型SKCM中。结论AS事件可能是SKCM预后的理想指标。关键特征基因MCF2L在野生型SKCM中发挥重要作用。
METHODS::Blue rubber bleb naevus syndrome (BRBNS) is an extremely rare venous malformation that often manifests as multiple haemangioma-like lesions in the skin and gastrointestinal tract. The drug sirolimus plays a key role in the signalling pathway of angiogenesis and subsequent development of BRBNS and its use has been described in several case reports. We present a case series of four patients with BRBNS who exhibited good treatment response to sirolimus. All four patients were administered oral sirolimus at doses of 1.0-1.5 mg/m2 /day with a target drug level of 5-10 ng/mL and median treatment duration of 20 months. All patients had a reduction in the size of the lesions and a normalization of coagulopathy with tolerable drug adverse reactions at follow-up. Sirolimus may be effective and safe in paediatric patients with BRBNS. Further prospective studies are suggested to evaluate the long-term effectiveness of this drug.
METHODS:BACKGROUND:Human papillomavirus (HPV) infections are associated with common dermatologic and nondermatologic diseases. Although HPV vaccines are well established as preventive measures for genital warts and cervical neoplasia, their use as therapeutic agents deserves greater attention. OBJECTIVE:To evaluate the use of HPV vaccine(s) as a treatment modality for cutaneous and/or mucosal disease. METHODS:A primary literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in January 2019 by using the PubMed and Cochrane databases. RESULTS:A total of 63 articles with 4439 patients were included. The majority of patients with cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas were successfully treated with HPV vaccination. Preliminary data on patients with pre-existing anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia is promising. LIMITATIONS:This review was limited by the lack of controls, patients' previous HPV vaccination status, and publication bias. CONCLUSION:The commercially available three-dose, quadrivalent HPV vaccine is a potential therapeutic option for the treatment of cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas. Noncommercially available HPV vaccines demonstrate therapeutic response for treating anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia. The vaccine's efficacy as an adjunct therapy for HPV-associated cutaneous and/or mucosal disease warrants further exploration.
METHODS::Our understanding of melanoma precursors and progression to melanoma has developed as a result of advances in the field of molecular diagnostics. We now better understand the potential for genetic heterogeneity within a single lesion. Combined tumors can pose a diagnostic challenge when deciding the line between benign and malignant, which in turn has direct implications for patient management. Primary cilia (PC) are ubiquitous sensory organelles that have essential functions in cellular proliferation, differentiation, and development. The ciliation index (percentage of ciliated melanocytes) has been shown to reliably differentiate melanoma, which fail to ciliate, from melanocytic nevi, which retain PC. We therefore analyzed the potential for using the ciliation index to differentiate benign and malignant components in combined melanocytic lesions. We collected patient samples (n = 10) of unequivocal combined lesions with both melanoma and associated nevus components. Melanocytes were highlighted with SOX10 and costained with gamma-Tubulin and acetylated alpha-Tubulin to highlight the basal body and cilium, respectively. The number of melanocytes retaining cilia under high-power microscopy was examined. The melanoma component had average of 4% ciliation (SD: 7%), whereas the associated nevus component was significantly higher with 59% ciliation (SD: 17%). These data show that PC may be a reliable means of distinguishing benign from malignant components within a single tumor. The ciliation index may be a helpful tool in distinguishing challenging cases of combined lesions of melanoma in situ with a dermal nevus component from invasive melanoma, thus promoting improved staging and clinical management.