A novel RNA sequencing-based prognostic nomogram to predict survival for patients with cutaneous melanoma: Clinical trial/experimental study.
- 作者列表："Tian J","Yang Y","Li MY","Zhang Y
BACKGROUND:Plenty of evidence has suggested that long non-coding RNAs (lncRNAs) have played a vital part may act as prognostic biomarkers in a variety of cancers. The aim of this study was to screen survival-related lncRNAs and to construct a lncRNA-based prognostic model in patients with cutaneous melanoma (CM). METHODS:We obtained lncRNAs expression profiles and clinicopathological data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. A lncRNA-based prognostic model was established in training set. The established prognostic model was evaluated, and validated in the validation set. Then, a prognostic nomogram combining the lncRNA-based risk score and clinicopathological characteristics was developed in training set, and assessed in the validation set. The accuracy of the model was evaluated by the discrimination and calibration plots. RESULTS:A total of 212 lncRNAs were identified to be differentially expressed in CM. After univariate analysis, LASSO penalized regression analysis, and multivariate analysis, 3 lncRNAs were used to construct risk score model. The proposed risk score model could divide patients into high-risk and low-risk groups with significantly different survival in both training set and validation set. The ROC curve showed good performance in survival prediction in both sets. Furthermore, the nomogram for predicting 3-, 5-, and 10-year OS was established based on lncRNA-based risk score and clinicopathologic factors. The prognostic accuracy of the risk model was confirmed by the discrimination and calibration plots in both training set and validation set. CONCLUSIONS:We established a novel three lncRNA-based risk score model and nomogram to predict overall survival of CM. The proposed nomogram may provide information for individualized treatment in CM patients.
背景: 大量证据表明，长链非编码rna (lncRNAs) 在多种癌症中起着至关重要的作用，可能作为预后生物标志物。本研究的目的是筛选生存相关lncRNA，并构建基于lncRNA的皮肤黑色素瘤 (CM) 患者预后模型。 方法: 我们从癌症基因组图谱 (TCGA) 和基因型-组织表达 (GTEx) 数据库中获得了lncRNAs表达谱和临床病理数据。在训练集中建立了基于lncRNA的预后模型。对建立的预后模型进行评价，并在验证集中进行验证。然后，在训练集中开发了结合基于lncRNA的风险评分和临床病理特征的预后列线图，并在验证集中进行评估。通过判别和校准图评价模型的准确性。 结果: 共鉴定出 212 个lncRNAs在CM中差异表达。经过单变量分析、LASSO惩罚回归分析和多变量分析，使用 3 个lncRNAs构建风险评分模型。所提出的风险评分模型可以将患者分为高风险组和低风险组，在训练集和验证集上的生存率均有显著差异。ROC曲线在两组中显示出良好的生存预测性能。此外，根据基于lncRNA的风险评分和临床病理因素建立了预测 3 、 5 和 10 年OS的列线图。风险模型的预后准确性通过训练集和验证集中的判别和校准图得到证实。 结论: 我们建立了一个新的三种基于lncRNA的风险评分模型和列线图来预测CM的总生存期。提出的列线图可能为CM患者的个体化治疗提供信息。
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.