Transcriptomic signatures related to the obesity paradox in patients with clear cell renal cell carcinoma: a retrospective cohort study
Abstract
Summary Background Obesity is associated with an increased risk of developing clear cell renal cell carcinoma (ccRCC) but, paradoxically, with improved oncologic outcomes. As the biologic mechanisms underlying this association are poorly understood, our study aimed to identify transcriptomic differences in primary tumor or peritumoral adipose tissue between obese and normal weight patients. Methods After confirming the inverse association between body mass index (BMI ≥ 30 vs < 30 kg/m2) and mortality in three independent clinical cohorts including 453 metastatic ccRCC patients treated with first-line VEGF-directed therapy from the Phase III COMPARZ clinical trial, 152 predominately early stage ccRCC patients from the Cancer Genome Atlas (TCGA), and a Memorial Sloan Kettering (MSK) observational cohort of 203 metastatic ccRCC patients treated with targeted immunotherapy using the Kaplan–Meier method and analyzed by log-rank test, we evaluated and validated primary tumor transcriptomic differences. We also compared gene expression differences in peritumoral adipose tissue from a prospectively collected cohort of patients with non-metastatic ccRCC. Wilcoxon rank-sum test was used to analyze significant differences in gene expression between groups and false discovery correction was performed using the Benjamini-Hochberg procedure. Findings A lower mortality rate was observed in obese patients versus normal weight patients in the in the locally advanced The Cancer Genome Atlas…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 453 participants or records.
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