Serum and Adipose Tissue mRNA Levels of ATF3 and FNDC5/Irisin in Colorectal Cancer Patients With or Without Obesity.

Huijuan Zhu,Nianrong Zhang,Fengying Gong,Hui Pan,Meijuan Liu,Linjie Wang,Kemin Yan,Hongbo Yang,Naishi Li,Guole Lin

doi:10.3389/fphys.2018.01125

Abstract

Objectives: To explore the activating transcription factor 3 (ATF3) and fibronectin type III domain-containing protein 5 (FNDC5)/irisin protein levels in serum and mRNA levels in subcutaneous and visceral white adipose tissue (sWAT and vWAT) in normal-weight (NW) and overweight/obese (OW/OB) patients with colorectal cancer (CRC).Methods: 76 CRC patients and 40 healthy controls were recruited. Serum ATF3 and irisin levels were detected by using ELISA kits, and the mRNA expression levels in sWAT and vWAT were measured by performing RT-qPCR.Results: The serum ATF3 levels were greater by 37.2%, whereas the irisin levels were lower by 23.3% in NW+CRC patients compared with those in healthy controls. CRC was independently associated with both ATF3 and irisin levels. The probability of CRC greater by 22.3-fold in individuals with high ATF3 levels compared with those with low ATF3 levels, whereas the risk of CRC in subjects with high irisin levels was lower by 78.0% compared to the risk in those with low irisin levels after adjustment for age, gender, BMI, and other biochemical parameters. Serum ATF3 and irisin could differentiate CRC patients from controls with receiver operating characteristic (ROC) curve areas of 0.745 (95% CI, 0.655–0.823) and 0.656 (95% CI, 0.561–0.743), respectively. The combination of ATF3 and irisin exhibited improved diagnosis value accuracy with ROC curve areas of 0.796 (95% CI, 0.710–0.866) as well as 72.6% sensitivity and 80.0% specificity.Conclusion: Increased ATF3 and reduced irisin levels were observed in sera from CRC patients. Individuals with high ATF3 and low irisin levels were more likely to have CRC. ATF3 and irisin represent potential diagnostic biomarkers for CRC patients.

Highlights

According to the annually updated nationwide statistics from the National Central Cancer Registry of China (NCCRC), the incidence of colorectal cancer (CRC) ranked as the fourth predominant cancer in men and the third in women
No significant difference in serum Activating transcription factor 3 (ATF3) levels was observed between NW+CRC and OW/OB+CRC patients
This decreased possibility of CRC remained after further adjustment for body mass index (BMI), fasting blood glucose (FBG), systolic blood pressure (SBP), and DBP based on Model 1 (Model 2, odds ratio (OR) = 0.17, 95% confidence intervals (CI) 0.05–0.56, P < 0.01) and total cholesterol (TC), HDL-C, TG, and low-density lipoprotein cholesterol (LDL-C) based on Model 2 (Model 3, OR = 0.22, 95% CI 0.06–0.83, P = 0.026)

Summary

Introduction

According to the annually updated nationwide statistics from the National Central Cancer Registry of China (NCCRC), the incidence of colorectal cancer (CRC) ranked as the fourth predominant cancer in men and the third in women. It is estimated that 347,900 individuals have been diagnosed with CRC, and 164,900 people died of CRC in 2013 in China (Chen et al, 2017). Both the incidence and mortality trends of CRC had significantly increased at the rates of 2.5 and 1.3%, respectively, from 2000 to 2013 in China (Chen et al, 2017). A recently updated review by Bardou et al (2013) reported that obesity was associated with a 30–70% increased risk of CRC compared with that in normal-weight people. The dysregulated secretion of adipokines in obese conditions contributes considerably to the pathogenesis of CRC (van Kruijsdijk et al, 2009; PrietoHontoria et al, 2011; Perez-Hernandez et al, 2014; Zhu et al, 2018)

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