Zhu Huijuan, Liu Meijuan, Zhang Nianrong, Pan Hui, Lin Guole, Li Naishi, Wang Linjie, Yang Hongbo, Yan Kemin, Gong Fengying
Key Laboratory of Endocrinology of National Health and Family Planning Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, China.
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, China.
Front Endocrinol (Lausanne). 2018 Apr 26;9:190. doi: 10.3389/fendo.2018.00190. eCollection 2018.
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, mRNA levels in sWAT were significantly reduced by 78.8% in OB + CRC in comparison with NW + CRC patients. mRNA levels were negatively associated with body mass index (BMI) in sWAT but positively correlated with BMI in vWAT. 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, = 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, = 0.04). The area under the receiver operating characteristic (ROC) curve of ZAG was 0.66 (95% CI 0.54-0.77, < 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.
探讨正常体重（NW）和超重/肥胖（OW/OB）的结直肠癌（CRC）患者血清、皮下及内脏白色脂肪组织（sWAT和vWAT）中锌-α2-糖蛋白（ZAG）、瘦素、高分子量脂联素（HMW-ADPN）和肿瘤坏死因子-α（TNF-α）水平。
共招募76例中国CRC患者（42例NW+CRC，34例OW/OB+CRC）和40例健康对照者。采用酶联免疫吸附测定法检测血清中相关脂肪因子水平，通过逆转录定量PCR法测定sWAT和vWAT中它们的mRNA水平。
与健康对照相比，NW+CRC组血清ZAG水平显著升高11.7%。与CRC患者的NW+CRC组相比，OW/OB+CRC组血清瘦素水平升高57.7%，而HMW-ADPN水平降低23.5%。此外，与NW+CRC患者相比，OB+CRC患者sWAT中的mRNA水平显著降低78.8%。sWAT中的mRNA水平与体重指数（BMI）呈负相关，而在vWAT中与BMI呈正相关。与NW+CRC患者相比，OB+CRC患者vWAT中的α mRNA水平显著升高2.8倍。特别是，CRC与血清ZAG水平独立相关。在调整年龄、性别和其他混杂因素后，血清ZAG水平处于高三分位数的参与者患CRC的风险比处于低三分位数的参与者高5.84倍[比值比（OR）=6.84，95%置信区间（CI）1.70-27.54，P=0.03]。瘦素水平处于高三分位数的参与者患CRC的风险仅为处于低三分位数参与者的10.7%（OR=0.11，95%CI 0.01-0.89，P=0.04）。ZAG的受试者工作特征（ROC）曲线下面积为0.66（95%CI 0.54-0.77，P<0.05）。血清ZAG的截断值为1.42μg/mL时，区分CRC患者与对照的敏感性和特异性分别为62.2%和69.2%。
CRC患者血清ZAG水平显著升高。与ZAG水平较低和瘦素水平较高的受试者相比，循环ZAG水平较高和瘦素水平较低的受试者更易患CRC。血清ZAG可能是中国人群中CRC的潜在诊断生物标志物。
