Oncogenic Foxl2 is a chromatin-remodeling pioneer transcription factor in adult-type ovarian granulosa cell tumors

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Comparative Transcriptomic Analysis of Primary and Recurrent Ovarian Granulosa Cell Tumors

View full abstracthttps://openworks.mdanderson.org/leading-edge/1027/thumbnail.jp

Comparative Tumor Microenvironment Analysis of Primary and Recurrent Ovarian Granulosa Cell Tumors

Adult-type granulosa cell tumors (aGCT) are rare ovarian sex cord tumors with few effective treatments for recurrent disease. The objective of this study was to characterize the tumor microenvironment (TME) of primary and recurrent aGCTs and to identify correlates of disease recurrence. Total RNA sequencing (RNA-seq) was performed on 24 pathologically confirmed, cryopreserved aGCT samples, including 8 primary and 16 recurrent tumors. After read alignment and quality-control filtering, DESeq2 was used to identify differentially expressed genes (DEG) between primary and recurrent tumors. Functional enrichment pathway analysis and gene set enrichment analysis was performed using “clusterProfiler” and “GSVA” R packages. TME composition was investigated through the analysis and integration of multiple published RNA-seq deconvolution algorithms. TME analysis results were externally validated using data from independent previously published RNA-seq datasets. A total of 31 DEGs were identified between primary and recurrent aGCTs. These included genes with known function in hormone signaling such as LHCGR and INSL3 (more abundant in primary tumors) and CYP19A1 (more abundant in recurrent tumors). Gene set enrichment analysis revealed that primarily immune-related and hormone-regulated gene sets expression was increased in recurrent tumors. Integrative TME analysis demonstrated statistically significant depletion of cancer-associated fibroblasts in recurrent tumors. This finding was confirmed in multiple independent datasets

Table S2 from Comparative Tumor Microenvironment Analysis of Primary and Recurrent Ovarian Granulosa Cell Tumors

Clinical Characteristics by Patient</p

Table S3 from Comparative Tumor Microenvironment Analysis of Primary and Recurrent Ovarian Granulosa Cell Tumors

Differentially Expressed Genes</p

Supplementary Figures 1-6 from Comparative Tumor Microenvironment Analysis of Primary and Recurrent Ovarian Granulosa Cell Tumors

S1. Heatmap of unsupervised hierarchical clustering of the top 1000 most variable genes.S2. Violin plots showing the expression levels of genes previously identified as differentially expressed genes between primary and recurrent tumors in Haltia et al., 2020.S3. Gene set enrichment analysis performed with GO terms and KEGG pathways showing that primarily immune-related and hormone-regulated gene sets expression are altered between primary and recurrent aGCTs.S4. Gene set enrichment analysis results showing that top enriched gene sets are significantly enriched in recurrent tumors in comparison with primary tumors.S5. Boxplot showing the fraction of each noncancerous cell type identified by CIBERSORTx (A) and xCell (B) in primary and recurrent tumor samples.S6. Heatmap showing the correlation between immune cells fractions.</p

Table S1 from Comparative Tumor Microenvironment Analysis of Primary and Recurrent Ovarian Granulosa Cell Tumors

RNA Sequencing QC Metrics</p