Abstract
Obesity is well accepted as crucial risk factor that plays a critical role in the initiation and progression of colorectal cancer (CRC). More specifically, visceral adipose tissue (VAT) in people with obesity could produce chronic inflammation and an altered profile expression of key transcription factors that promote a favorable microenvironment to colorectal carcinogenesis. For this, the aim of this study was to explore the relationship between adipogenic and inflammatory transcription factors in VAT from nonobese, obese, and/or CRC patients. To test this idea, we studied the expression and methylation of CCAAT-enhancer binding protein type alpha (C/EBP-α), peroxisome proliferator-activated receptor gamma (PPAR-γ), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) in VAT from non-obese control, non-obese CRC subjects, overweight/obese control, and overweight/obese CRC patients and their correlation with anthropometric and biochemical variables. We found decreased expression of C/EBP-α in overweight/obese CRC patients in comparison with overweight/obese control subjects. PGC-1α and NF-κB were overexpressed in CRC patients independently of the BMI. NF-κB promoter was hypomethylated in overweight/obese CRC patients when compared to overweight/obese control individuals. In addition, multiple significant correlations between expression, methylation, and biochemical parameters were found. Finally, linear regression analysis showed that the expression of C/EBP-α and NF-κB and that NF-κB methylation were associated with CRC and able to explain up to 55% of CRC variability. Our results suggest that visceral adipose tissue may be a key factor in tumor development and inflammatory state. We propose C/EBP-α, PGC-1α and NF-κB to be interesting candidates as potential biomarkers in adipose tissue for CRC patients.
Highlights
Colorectal cancer (CRC) is considered the most important public health concern, which constitutes the third most commonly occurring cancer worldwide in both men and women [1]
A study was in line with our results, which reported that nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) in visceral adipose tissue (VAT) was highly expressed in colorectal cancer (CRC) patients but without taking the effect of the body mass index (BMI), as we showed in our study [6]
Our results suggests that C/EBP-α, proliferator-activated receptor gamma coactivator 1-α (PGC-1α), and NF-κB are important to consider as potential biomarkers in the context of obesity and CRC, as their expression and methylation status could provide a new insight into how VAT is implicated in obesity-related CRC
Summary
Colorectal cancer (CRC) is considered the most important public health concern, which constitutes the third most commonly occurring cancer worldwide in both men and women [1]. It is well known that visceral adipose tissue (VAT) in people with obesity could produce chronic inflammation and an altered profile expression of key transcription factors that promote a favorable microenvironment to colorectal carcinogenesis [5,6]. This study showed that C/EBP-α expression enhances CRC cells migration and invasion in vitro as well as metastasis in vivo [11]. As for PPAR-γ expression, a study reported that the expression profile of PPAR-γ was significantly lower in primary tumors when compared to normal colon for CRC patients [12]. To date, there is a lack of studies of the expression profile, methylation, and functional significance in VAT of C/EBP-α and PPAR-γ in obesity-related CRC
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