Prieske Katharina, Alawi Malik, Jaeger Anna, Wankner Maximilian Christian, Eylmann Kathrin, Reuter Susanne, Lebok Patrick, Burandt Eike, Blessin Niclas C, Schmalfeldt Barbara, Oliveira-Ferrer Leticia, Joosse Simon A, Woelber Linn
Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Cancers (Basel). 2021 Dec 19;13(24):6372. doi: 10.3390/cancers13246372.
To date, therapeutic strategies in vulvar squamous cell carcinoma (VSCC) are lacking molecular pathological information and targeted therapy hasn't been approved in the treatment of VSCC, yet. Two etiological pathways are widely accepted: HPV induced vs. HPV independent, associated with chronic skin disease, often harboring mutations (mut). The aim of this analysis was to analyze the RNA expression patterns for subtype stratification on VSCC samples that can be integrated into the previously performed whole exome sequencing data for the detection of prognostic markers and potential therapeutic targets. We performed multiplex gene expression analysis (NanoString) with 770 genes in 24 prior next generation sequenced samples. An integrative data analysis was performed. Here, 98 genes were differentially expressed in TP53mut vs. HPV+ VSCC, in the TP53mut cohort, where 56 genes were upregulated and 42 were downregulated in comparison to the HPV+ tumors. Aberrant expression was primarily observed in cell cycle regulation, especially in HPV+ disease. Within the TP53mut group, a distinct cluster was identified that was correlated to a significantly worse overall survival ( = 0.017). The RNA expression profiles showed distinct patterns with regard to the known VSCC subtypes and could potentially enable further subclassification in the TP53mut groups.
迄今为止,外阴鳞状细胞癌(VSCC)的治疗策略缺乏分子病理学信息,且靶向治疗尚未被批准用于VSCC的治疗。两种病因途径被广泛认可:HPV诱导型与HPV非依赖型,后者与慢性皮肤病相关,常伴有突变(mut)。本分析的目的是分析VSCC样本的RNA表达模式,以便进行亚型分层,从而可将其整合到先前进行的全外显子测序数据中,用于检测预后标志物和潜在的治疗靶点。我们对24个先前进行过二代测序的样本中的770个基因进行了多重基因表达分析(NanoString)。进行了综合数据分析。在此,98个基因在TP53突变型与HPV阳性VSCC中差异表达,在TP53突变型队列中,与HPV阳性肿瘤相比,56个基因上调,42个基因下调。异常表达主要出现在细胞周期调控中,尤其是在HPV阳性疾病中。在TP53突变型组中,鉴定出一个与总体生存率显著较差相关的独特聚类(P = 0.017)。RNA表达谱在已知的VSCC亚型方面显示出不同的模式,并且有可能在TP53突变型组中实现进一步的亚分类。