Abstract
To explore zinc-α2-glycoprotein (ZAG), leptin, high-molecular-weight adiponectin (HMW-ADPN), and tumor necrosis factor-alpha (TNF-α) levels in serum and subcutaneous and visceral white adipose tissue (sWAT and vWAT) among normal weight (NW) and overweight/obese (OW/OB) patients with colorectal cancer (CRC). A total of 76 Chinese CRC patients (42 NW + CRC, 34 OW/OB + CRC) and 40 healthy controls were recruited. Serum levels of the adipokines of interest were measured by an enzyme-linked immunosorbent assay method, and their mRNA levels in sWAT and vWAT were determined by reverse transcription quantitative PCR methods. Serum ZAG levels in the NW + CRC group were significantly increased by 11.7% compared with the healthy controls. Serum leptin levels in the OW/OB + CRC group were found to be increased by 57.7%, while HMW-ADPN levels were decreased by 23.5% when compared with the NW + CRC group of CRC patients. Additionally, ZAG mRNA levels in sWAT were significantly reduced by 78.8% in OB + CRC in comparison with NW + CRC patients. ZAG mRNA levels were negatively associated with body mass index (BMI) in sWAT but positively correlated with BMI in vWAT. TNF-α mRNA levels in vWAT of OB + CRC patients were significantly increased by 2.8-fold when compared with NW + CRC patients. In particular, CRC was independently associated with serum ZAG levels. The risk of CRC in participants with high tertile serum ZAG levels was 5.84-fold higher than in those with low tertile ZAG levels after adjusting for age, gender, and other confounders [odds ratio (OR) = 6.84, 95% confidence interval (CI) 1.70-27.54, P = 0.03]. The CRC risk in participants with high tertile leptin levels was only 10.7% of those with low tertile leptin levels (OR = 0.11, 95% CI 0.01-0.89, P = 0.04). The area under the receiver operating characteristic (ROC) curve of ZAG was 0.66 (95% CI 0.54-0.77, P < 0.05). At the cutoff value of 1.42 µg/mL serum ZAG, the sensitivity and specificity for differentiating patients with CRC from controls were 62.2 and 69.2%, respectively. Serum ZAG levels were significantly increased in CRC patients. Subjects with higher circulating ZAG and lower leptin levels were more likely to have CRC than those with lower ZAG and higher leptin levels. Serum ZAG might be a potential diagnostic biomarker for CRC in the Chinese population.
Highlights
Colorectal cancer (CRC) is the third most predominant cancer in men and the second in women around the world [1]
The mechanisms by which obesity contributes to the occurrence and development of CRC are multifactorial and have not yet been fully elucidated, accumulating evidence has shown that adipose tissue dysfunction in obesity, which causes an alteration of adipokine secretion, may mediate the relationship between obesity and CRC [6,7,8]
Further studies in Chinese populations reported that ZAG was upregulated at the transcriptional and posttranscriptional levels in fresh colon cancer tissues [27], suggesting that ZAG might be a potential biomarker for CRC in both Western and Eastern populations
Summary
Colorectal cancer (CRC) is the third most predominant cancer in men and the second in women around the world [1]. The mechanisms by which obesity contributes to the occurrence and development of CRC are multifactorial and have not yet been fully elucidated, accumulating evidence has shown that adipose tissue dysfunction in obesity, which causes an alteration of adipokine secretion, may mediate the relationship between obesity and CRC [6,7,8]. Among these adipokines, adiponectin, leptin, and tumor necrosis factor-alpha (TNF-α) have been largely reported to be implicated in the development of CRC. Higher serum levels of TNF-α have been shown to be associated with an increased risk of colorectal adenomas [17]
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