Association between differential gene expression and body mass index among endometrial cancers from The Cancer Genome Atlas Project.
The Cancer Genome Atlas (TCGA) identified four integrated clusters for endometrial cancer (EC): POLE, MSI, CNL and CNH. We evaluated differences in gene expression profiles of obese and non-obese women with EC and examined the association of body mass index (BMI) within the clusters identified in TCGA.



TCGA RNAseq data was used to identify genes related to increasing BMI among ECs. The POLE, MSI and CNL clusters were composed mostly of endometrioid EC. Patient BMI was compared between these three clusters with one-way ANOVA. Association between gene expression and BMI was also assessed while adjusting for confounding effects of potential confounding factors. p-Values testing the association between gene expression and BMI were adjusted for multiple hypothesis testing over the 20,531 genes considered.



Mean BMI was statistically different between the ECs in the CNL (35.8) versus POLE (29.8) cluster (p=0.006) and approached significance for the MSI (33.0) versus CNL (35.8) cluster (p=0.05). 181 genes were significantly up- or down-regulated with increasing BMI in endometrioid EC (q-value<0.01), including LPL, IRS-1, IGFBP4, IGFBP7 and the progesterone receptor. DAVID functional annotation analysis revealed significant enrichment in "cell cycle" (adjusted p-value=1.5E-5) and "DNA metabolic processes" (adjusted p-value=1E-3) for the identified genes.



Obesity related genes were found to be upregulated with increasing BMI among endometrioid ECs. Patients with POLE tumors have the lowest median BMI when compared to MSI and CNL. Given the heterogeneity among endometrioid EC, consideration should be given to abandoning the Type I and II classification of EC tumors.
Division of Gynecologic Oncology, University of North Carolina, Chapel Hill, NC, United States; Lineberger Comprehensive Cancer Center, Chapel Hill, NC, United States.
Dario R
DR
Roque
Lineberger Comprehensive Cancer Center, Chapel Hill, NC, United States; Department of Nutrition, University of North Carolina, Chapel Hill, NC, United States.
Liza
L
Makowski
Department of Mathematics & Statistics, Laval University, Québec, Canada.
Ting-Huei
TH
Chen
Division of Gynecologic Oncology, University of North Carolina, Chapel Hill, NC, United States; Department of Biostatistics, University of North Carolina, Chapel Hill, NC, United States.
Naim
N
Rashid
Lineberger Comprehensive Cancer Center, Chapel Hill, NC, United States; Division of Hematology & Oncology, University of North Carolina, Chapel Hill, NC, United States.
D Neil
DN
Hayes
Division of Gynecologic Oncology, University of North Carolina, Chapel Hill, NC, United States; Lineberger Comprehensive Cancer Center, Chapel Hill, NC, United States. Electronic address: victoria_baejump@med.unc.edu.
Victoria
V
Bae-Jump
D015992:Body Mass Index; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000378:metabolism; D030541:Databases, Genetic; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics / Q000379:methods; D006801:Humans; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome; D015854:Up-Regulation