Abstract:
Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma that is frequently divided into Merkel cell polyomavirus negative and positive tumors due their distinct genomic and transcriptomic profiles, and disease outcomes. Although some prognostic factors in MCC are known, tumorigenic pathways, which that explain outcome differences in MCC are not fully understood. We investigated transcriptomes of 110 tissue samples of a formalin-fixed, paraffin-embedded MCC series by RNA sequencing to identify genes showing a bimodal expression pattern and predicting outcome in cancer and that potentially could play a role in tumorigenesis. We discovered 19 genes among which IGHM, IGKC, NCAN, OTOF, and USH2A were associated also with overall survival (all p-values < 0.05). From these genes, NCAN (neurocan) expression was detected in all 144 MCC samples by immunohistochemistry. Increased NCAN expression was associated with presence of Merkel cell polyomavirus DNA (p = 0.001) and viral large T antigen expression in tumor tissue (p = 0.004) and with improved MCC-specific survival (p = 0.027) and overall survival (p = 0.034). We conclude that NCAN expression is common in MCC, and further studies are warranted to investigate its role in MCC tumorigenesis.
摘要:
默克尔细胞癌(MCC)是一种罕见的皮肤神经内分泌癌,由于其独特的基因组和转录组学特征,通常分为默克尔细胞多瘤病毒阴性和阳性肿瘤。和疾病结果。虽然MCC的一些预后因素是已知的,致瘤途径,解释MCC结果差异的原因还没有完全理解。我们调查了福尔马林固定的110个组织样本的转录组,石蜡包埋的MCC系列,通过RNA测序来鉴定显示双峰表达模式和预测癌症结局的基因,这些基因可能在肿瘤发生中发挥作用。我们发现了19个基因,其中IGHM,IGKC,NCAN,OTOF,和USH2A也与总生存期相关(所有p值<0.05)。从这些基因中,通过免疫组织化学在所有144个MCC样品中检测到NCAN(神经聚糖)表达。NCAN表达的增加与Merkel细胞多瘤病毒DNA的存在(p=0.001)和肿瘤组织中病毒大T抗原的表达(p=0.004)以及MCC特异性生存率(p=0.027)和总生存率(p=0.034)的提高有关。我们得出结论,NCAN表达在MCC中很常见,并且需要进一步的研究来研究其在MCC肿瘤发生中的作用。