Boughanem Hatim, Cabrera-Mulero Amanda, Hernández-Alonso Pablo, Bandera-Merchán Borja, Tinahones Alberto, Tinahones Francisco José, Morcillo Sonsoles, Macias-Gonzalez Manuel
Biomedical Research Institute of Malaga (IBIMA), Faculty of Science, University of Malaga, 29010 Málaga, Spain.
Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, University of Malaga (IBIMA), 29010 Málaga, Spain.
Cancers (Basel). 2019 Oct 24;11(11):1629. doi: 10.3390/cancers11111629.
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.
肥胖是公认的关键风险因素，在结直肠癌（CRC）的发生和发展中起着至关重要的作用。更具体地说，肥胖人群的内脏脂肪组织（VAT）可产生慢性炎症，并改变关键转录因子的表达谱，从而促进有利于结直肠癌发生的微环境。因此，本研究的目的是探讨非肥胖、肥胖和/或CRC患者VAT中脂肪生成和炎症转录因子之间的关系。为了验证这一想法，我们研究了非肥胖对照、非肥胖CRC受试者、超重/肥胖对照以及超重/肥胖CRC患者VAT中CCAAT增强子结合蛋白α型（C/EBP-α）、过氧化物酶体增殖物激活受体γ（PPAR-γ）、过氧化物酶体增殖物激活受体γ共激活因子1-α（PGC-1α）和活化B细胞核因子κ轻链增强子（NF-κB）的表达和甲基化情况，以及它们与人体测量和生化变量的相关性。我们发现，与超重/肥胖对照受试者相比，超重/肥胖CRC患者中C/EBP-α的表达降低。无论BMI如何，CRC患者中PGC-1α和NF-κB均过表达。与超重/肥胖对照个体相比，超重/肥胖CRC患者中NF-κB启动子低甲基化。此外，还发现了表达、甲基化和生化参数之间的多个显著相关性。最后，线性回归分析表明，C/EBP-α和NF-κB的表达以及NF-κB甲基化与CRC相关，并且能够解释高达55%的CRC变异性。我们的结果表明，内脏脂肪组织可能是肿瘤发展和炎症状态的关键因素。我们提出C/EBP-α、PGC-1α和NF-κB作为CRC患者脂肪组织中潜在生物标志物的有趣候选物。
