Sofya Marchenko

Figure S2 displays the Proportions of Molecular subtypes of LTS and STS in the Charité cohort and n the TCGA cohort.

Figure S5 shows Candidate Genes in the Charité Cohort and Correlations among candidate genes and Literature research results for candidate genes.

The Table S1 shows the Patient ID, Cancer Stage and the Residual _Tumor status of the TCGA paired cohort grouped by the Survival Group.

Table S4 displays the characteristics and subtypes of the Charité cohort.

Purpose:The late-stage diagnosis and the aggressiveness of high-grade serous tubo-ovarian carcinoma (HGSC) often result in poor survival outcomes, yet some patients exhibit an exceptionally long survival rate. This study aimed to identify molecular profiles associated with long-/short-term survival in HGSC, with the goal of better understanding protective factors and developing new treatments.Experimental Design:To discover molecular drivers causing the aggressiveness of HGSC, tumor samples from 12 long-term HGSC survivors (>7 years overall survival) and 12 short-term survivors (<1 year overall survival) were analyzed using targeted RNA sequencing followed by computational analysis. We investigated differentially expressed genes and their functional relevance, inferred differences in cell type composition and signaling pathways, as well as mutation status. To validate our findings, we simulated our study design by using HGSC The Cancer Genome Atlas dataset samples. We evaluated differential patterns of gene expression between these two groups and developed molecular profiles of HGSC that correlate with survival phenotypes.Results:Besides known molecular cancer drivers and indicators of poor prognosis, we identified specific transcriptional changes between short- and long-term survivors of HGSC, which indicate that immune processes play a fundamental role in long-term survivors. Our computational analysis reveals an important role for the ensemble of IFN-γ signaling and the RFX transcription factors, as well as the immune cell composition of the tumor microenvironment.Conclusions:Specific immunologic requirements involving IFN-γ signaling and affected pathways seem to be relevant for long-term survival in the generally considered nonimmunogenic HGSC, necessitating further research to improve diagnostic strategies and targeted therapies.

Figure S10 displays differences in celltypes between the cohorts A) for LTS and B) for STS based on CIBERSORT results.

Figure S6 presents Boxplots showing differences in BRCA1/2, KRAS, RB1, CCNE1 expression between LTS and STS in the Charité cohort.

Figure S1 shows a REMARK Diagram of the Charité Cohort construction.

Figure S3 shows the Gene count Distribution before and after quality filtering in the Charité Cohort and in the TCGA subcohort.

Table S2 shows the settings for digital image analysis in QuPath for the three IHC markers (CD3,CD4, CD8)