Details

Autor(en) / Beteiligte

• Zwimpfer, Tibor A
• Lombardo, Flavio
• Rimmer, Natalie
• Götze, Sandra
• Singer, Franziska
• Bertolini, Anne
• Montavon, Céline
• Kurzeder, Christian
• Jacob, Francis
• Heinzelmann-Schwarz, Viola

Titel

174 Integrated multi-omic and clinicopathological analysis of vulvar squamous cell carcinoma: identification of predictive biomarkers for personalized treatment

Ist Teil von

• International journal of gynecological cancer, 2023, Vol.33 (Suppl 3), p.A364-A364

Ort / Verlag

Oxford: BMJ Publishing Group LTD

Erscheinungsjahr

2023

Link zum Volltext

Beschreibungen/Notizen

• Introduction/BackgroundVulvar cancer responds poorly to systemic treatment and in contrast to other gynecological cancers, targeted therapies remain at an early stage. Interactions of clinical, immune, and molecular biomarkers remain poorly understood for this rare cancer type. Here, we characterized the proteogenome of vulvar squamous cell carcinoma (vSCC) and provide a computational workflow to integrate publicly available data to study this rare and aggressive cancer type.MethodologyWhole exome sequencing, bulk RNA-sequencing, clinicopathological, and proteomics data from 23 patients with vSCC were analyzed. In addition, a total of 5543 women-derived TCGA genomic and transcriptomics sequencing data were obtained for this analysis.ResultsOur cohort consisted of 34.8% human papillomavirus (HPV)+ and 65.2% HPV- vSCC patients. Early FIGO stage was significantly associated with HPV- status (12% (1/8) vs. 86% (12/15), p<0.001). TP53 and CDKN2 were mutually exclusive to HPV+. Patients being HPV+ revealed a higher frequency in PIK3CA alterations with 37.5% vs. 6.7% in HPV-. TYMS which is considered the primary site of action for 5-fluorouracil was significantly higher expressed in HPV+ patients (log2FC=1.7497, p<0.001). We identified unique single and doublet base substitution signatures in vSCC indicating defective DNA mismatch-repair and correlation with age. Tongue SCC (tSCC) was identified as a comparison cohort supported by different clustering methods of conjoint RNA-seq and clinicopathological data, derived from TCGA. vSCC was associated with elevated activated mast cells (p=0.0031), monocytes (p=0.0027), and M2 macrophages (p<0.001) compared to tSCC, independent of the HPV status.ConclusionvSCC can be further distinguished by HPV status, somatic gene alterations and tumour microenvironment, while a similar cancer tissue has been identified with tSCC. Further analysis is targeted at identifying molecular signatures serving as biomarkers in vSCC and to suggest alternative treatment options of drugs already in use in tSCC or other cancer types.DisclosuresAll authors declare that they have no conflicts of interest.