Comprehensive Multiomics Analysis of Endometrial Cancer

We downloaded the TCGA RNA-Seq data (HTSeq Count) of EC using TCGAbiolink [25 (link)]. The TCGA MC3 files were retrieved from The Genomic Data Commons (GDC) portal to analyze the mutation profile of EC patients. The cBioportal was used to obtain the segmented copy number variation datasets [26 (link)]. We considered TCGA-Clinical Data Resource (CDR) to retrieve the corresponding clinical annotation for EC patients [27 (link)]. For validation, the microarray series dataset (GSE17025, Affymetrix Human Genome U133 Plus 2.0 Array), consisting of 91 EC samples, was downloaded from the NCBI GEO database using the GEOquery package [28 (link)]. We employed the human genome-scale metabolic model (HMR2.0) to study cancer metabolism. The model consists of 8181 reactions, 6006 metabolites, and 3765 genes, which describe the standard metabolic processes of a human cell.
The TCGA RNA-Seq dataset consists of 565 samples, of which 542 are primary tumor samples (sample type code—01) and 23 are tumor-matched normal samples (sample type code—11). We used variance-stabilizing transformation (VST) to normalize the RNA-Seq raw count data. The validation microarray dataset comprises 79 endometrioid and 12 papillary serous samples with various grades. We normalized the microarray data using Affymetrix’s MAS5.0 algorithm and log₂ transformation.