Abstract
The rising incidence and mortality of endometrial cancer (EC) in the United States calls for an improved understanding of the disease's progression. Current methodologies for diagnosis and treatment rely on the use of cell lines as models for tumor biology. However, due to inherent heterogeneity and differential growing environments between cell lines and tumors, these comparative studies have found little parallels in molecular signatures. As a consequence, the development and discovery of preclinical models and reliable drug targets are delayed. In this study, we established transcriptome parallels between cell lines and tumors from The Cancer Genome Atlas (TCGA) with the use of optimized normalization methods. We identified genes and signaling pathways associated with regulating the transformation and progression of EC. Specifically, the LXR/RXR activation, neuroprotective role for THOP1 in Alzheimer’s disease, and glutamate receptor signaling pathways were observed to be mostly downregulated in advanced cancer stage. While some of these highlighted markers and signaling pathways are commonly found in the central nervous system (CNS), our results suggest a novel function of these genes in the periphery. Finally, our study underscores the value of implementing appropriate normalization methods in comparative studies to improve the identification of accurate and reliable markers.
Highlights
Endometrial cancer (EC) is a common gynecologic malignancy in the United States with an estimated 66,570 new cases and 12,940 deaths in 2021 [1]
In order to better understand genes that may be driving stage progression in EC, we identified a set of genes for each stage comparison by merging cell lines and The Cancer Genome Atlas (TCGA) patients according to stage and using volcano plots that highlights differentially expressed genes (DEG) that are up- or downregulated (p < 0.05; at least |log2 fold change (FC)| ≥ 1)
We established transcriptome similarities between the cell lines used in this study and patient tumor samples from TCGA database
Summary
Endometrial cancer (EC) is a common gynecologic malignancy in the United States with an estimated 66,570 new cases and 12,940 deaths in 2021 [1]. While EC is presented more commonly amongst older women, it is the only gynecologic cancer with increased incidences at earlier age onset with a concomitant rise in mortality rate [2,3,4,5]. Reports that analyzed the Surveillance Epidemiology, and End Results (SEER) database suggest that early tumor staging (stage I and stage II) is correlated to better prognosis and a higher www.oncotarget.com. The survival rates drop dramatically from 96 to 18–70% respectively [1, 6]. The OS is relatively high with early stage detection, the vast majority of late stage EC exhibits a dramatic decline in survival due to lowered responses to radiation, hormone, and non-hormone based treatments [7]. Staging can be inaccurate and limited in predicting responses to therapy, as some of the early stage lesions display aggressive metastatic behavior, tumor heterogeneity, ambiguous histology, and overlapping molecular characteristics [8,9,10,11,12,13,14,15,16]
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