Mining database for the expression and gene regulation network of JAK2 in skin cutaneous melanoma.
- 作者列表："Zhang W","Zhao H","Chen J","Zhong X","Zeng W","Li Z","Zhou J","He Z","Tang S
BACKGROUND:Skin cutaneous melanoma (SKCM) is the most common subtype of skin malignancy, with ever-increasing incidence, mortality, and disease burden. Dysregulation of JAK-STATs signaling pathway is involved in the pathogenesis and progression of cancers, thus affecting the prognosis of cancer patients. The function of JAKs in SKCM is still not clarified. METHODS:A total of five online portal (GEPIA, TIMER, GeneMANIA, LinkedOmics, and GSCALite) is used to mine the expression and gene regulation network JAK2 in SKCM. RESULTS:JAK2 expression was downregulated in SKCM and significantly associated with pathological stage and the prognosis of patients. The functions of JAK2 and associated genes were primarily involved in the DNA recombination, cell cycle checkpoint, metabolic process, NOD-like receptor signaling pathways, p53 signaling pathway and apoptosis. JAK2 level was significantly correlated with the abundance of immune cells and the level of immune biomarkers. Low expression of JAK2 were resistant to QL-VIII-58, TL-1-85, Ruxolitinib, TG101348 and Sunitinib. CONCLUSIONS:Our results reveal the expression and gene regulation network of JAK2 in skin cutaneous melanoma, providing more evidences about the role of JAK2 in carcinogenesis.
背景: 皮肤皮肤黑色素瘤 (SKCM) 是最常见的皮肤恶性肿瘤亚型，其发病率、死亡率和疾病负担不断增加。JAK-STATs信号通路的失调参与了癌症的发病和进展，从而影响癌症患者的预后。SKCM中JAKs的功能仍未阐明。 方法: 使用总共 5 个在线门户 (GEPIA、TIMER、GeneMANIA、linkdomics和GSCALite) 挖掘SKCM中的表达和基因调控网络JAK2。 结果: JAK2 在SKCM中表达下调，并与病理分期和患者预后显著相关。JAK2 及其相关基因的功能主要涉及DNA重组、细胞周期检查点、代谢过程、NOD样受体信号通路、p53 信号通路和细胞凋亡。JAK2 水平与免疫细胞丰度和免疫生物标志物水平显著相关。JAK2 低表达对QL-VIII-58 、TL-1-85 、Ruxolitinib、TG101348 和舒尼替尼耐药。 结论: 我们的结果揭示了JAK2 在皮肤黑素瘤中的表达和基因调控网络，为JAK2 在癌变过程中的作用提供了更多的证据。
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.