Transcriptome Analysis in Vulvar Squamous Cell Cancer

SIMPLE SUMMARY: The number of women, especially younger women, diagnosed with vulvar cancer, has been rising mainly due to the infection with human papilloma virus (HPV) over the last years. In contrast to other tumor entities, limited information on the underlying genetic changes is available, and thus treatment advances, especially the development of personalized treatments, are hampered. We aimed to explore the RNA expression profiles in a group of 24 vulvar cancer samples in order to detect potential prognostic markers and therapeutic targets in order to establish to a more profound understanding of vulvar cancer carcinogenesis. ABSTRACT: 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 TP53 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 (p = 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