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. 2022 Sep 29;23(19):11471.
doi: 10.3390/ijms231911471.

Investigation of Transcriptome Patterns in Endometrial Cancers from Obese and Lean Women

Konii Takenaka  1 , Ashton Curry-Hyde  1 , Ellen M Olzomer  1 , Rhonda Farrell  2 , Frances L Byrne  1 , Michael Janitz  1
Affiliations

Investigation of Transcriptome Patterns in Endometrial Cancers from Obese and Lean Women

Konii Takenaka et al. Int J Mol Sci. .

Abstract

Endometrial cancer is the most common gynaecological malignancy in developed countries. One of the largest risk factors for endometrial cancer is obesity. The aim of this study was to determine whether there are differences in the transcriptome of endometrial cancers from obese vs. lean women. Here we investigate the transcriptome of endometrial cancer between obese and lean postmenopausal women using rRNA-depleted RNA-Seq data from endometrial cancer tissues and matched adjacent non-cancerous endometrial tissues. Differential expression analysis identified 12,484 genes (6370 up-regulated and 6114 down-regulated) in endometrial cancer tissues from obese women, and 6219 genes (3196 up-regulated and 3023 down-regulated) in endometrial cancer tissues from lean women (adjusted p-value < 0.1). A gene ontology enrichment analysis revealed that the top 1000 up-regulated genes (by adjusted p-value) were enriched for growth and proliferation pathways while the top 1000 down-regulated genes were enriched for cytoskeleton restructure networks in both obese and lean endometrial cancer tissues. In this study, we also show perturbations in the expression of protein coding genes (HIST1H2BL, HIST1H3F, HIST1H2BH, HIST1H1B, TTK, PTCHD1, ASPN, PRELP, and CDH13) and the lncRNA MBNL1-AS1 in endometrial cancer tissues. Overall, this study has identified gene expression changes that are similar and also unique to endometrial cancers from obese vs. lean women. Furthermore, some of these genes may serve as prognostic biomarkers or, possibly, therapeutic targets for endometrial cancer.

Keywords: RNA-seq; endometrial cancer; gene expression; molecular signatures.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Venn diagrams summarising genes by biotype in EC and control tissue from obese women. Presented are the (A) total genes regardless of biotype; (B) protein coding genes; (C) long non-coding (lncRNA); (D) pseudogenes; and (E) other. Numbers within Venn diagrams display the number of genes common to both EC and control (overlapping circles in yellow), unique to EC (orange), and unique to control tissue (blue).
Figure 2
Figure 2
Principal component analysis (PCA) of EC and control tissue of the top 1000 most varied genes by fold-change from obese and lean women. EC samples in orange and control tissue in blue; circles represent the obese cohort and triangles represent the lean cohort.
Figure 3
Figure 3
Differential expression analysis between EC and control tissues from the obese cohort. (A) Volcano plot of differentially expressed genes. The x-axis is the fold-change in gene expression between EC and control tissues and the y-axis is the log10 (adjusted p-value). Green, purple, and grey dots represent up-regulated, down-regulated, and non-differentially expressed genes in EC, respectively. (B) Stacked bar charts show the percentage of each biotype of up-regulated genes in shades of green and down-regulated genes in shades of purple.
Figure 4
Figure 4
Expression patterns of selected differentially expressed gene between control and EC samples from the obese cohort. Scatter plots and box and whisker plots present expression levels in counts per million (CPM) for EC compared to control tissue with boxes denoting the interquartile range (IQR), median represented by horizontal bar within the IQR, and vertical bars indicating minimum and maximum values. (A–E) Expression patterns of the top five up-regulated genes in EC and (F–J) top five down-regulated genes in EC by adjusted p-value. The y-axis shows gene expression in CPM, dots indicate the individual sample expression values for EC (blue) and control tissue (orange).
Figure 5
Figure 5
Gene ontology enrichment analysis of protein coding genes in EC from obese women. (A) Top 1000 up-regulated genes by adjusted p-value. (B) Top 1000 down-regulated genes by adjusted p-value.
Figure 6
Figure 6
Venn diagram of differentially expressed genes (up- and down-regulated) across obese and lean cohort of women.
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