High expression of FABP4 in colorectal cancer and its clinical significance

脂肪酸结合蛋白 4 (FABP4) 在结直肠癌中的高表达及其临床意义

Abstract

Objective

To investigate the relationship between the fatty acid-binding protein 4 (FABP4) and colorectal cancer (CRC).

Methods

Using an enzyme-linked immunosorbent assay (ELISA), we measured the expression of FABP4 in plasma of 50 patients who underwent surgery for CRC from October 2017 to May 2018 and 50 healthy controls. The content of the visceral fat area (VFA) as seen with abdominal computed tomography (CT) scanning was measured by ImageJ software. The expression levels of FABP4, E-cadherin, and Snail proteins in CRC and adjacent tissues were determined by immunohistochemistry.

Results

The mean concentration of plasma FABP4 of CRC patients was higher than that of the control group (22.46 vs. 9.82 ng/mL; P<0.05). The concentration of plasma FABP4 was related to the tumor, node, metastatis (TNM) stage and lymph node metastasis and was independent of age, body mass index (BMI), tumor size and location, and the degree of differentiation of CRC. The concentration of plasma FABP4 was positively correlated with high VFA and lipoprotein-a (LPA) (P<0.05); but it was not correlated with total cholesterol (TG), total triglyceride (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), or apolipoprotein AI (Apo-AI). The expression of FABP4 protein in CRC tissues was positively correlated with the degree of CRC differentiation, tumor stage, and lymph node metastasis. The level of FABP4 protein was negatively correlated with E-cadherin protein (r= −0.3292, P=0.0196) and positively correlated with Snail protein (r=0.5856, P<0.0001).

Conclusions

High LPA and VFA were risk factors for increased plasma FABP4 in CRC patients. FABP4 protein was highly expressed in CRC tissues and associated with TNM stage, differentiation, and lymph node metastasis of CRC. The level of FABP4 in CRC tissue was correlated with E-cadherin and Snail expression, suggesting that FABP4 may promote CRC progression related to epithelial-mesenchymal transition (EMT).

概要

目的

探讨脂肪酸结合蛋白 4 (FABP4) 与结直肠癌 (CRC)的关系.

创新点

结直肠癌患者血浆 FABP4 浓度明显高于对照组 (22.46 ng/mL vs. 9.82 ng/mL, P<0.05). 血浆 FABP4 浓度与肿瘤、 淋巴结、 转移灶 (TNM) 分期和淋巴结转移有关, 与年龄、 身体质量指数 (BMI)、 肿瘤大小、 部位和结直肠癌分化程度无关. 血浆 FABP4 浓度与高内脏脂肪区 (VFA) 和脂蛋白 a (LPA) 呈正相关 (P<0.05), 与总胆固醇 (TG)、 总甘油三酯 (TC)、 低密度脂蛋白 (LDL)、 高密度脂蛋白 (HDL) 以及载脂蛋白 AI 无相关性. FABP4 蛋白在结直肠癌组织中的表达与大肠癌分化程度、 肿瘤分期和淋巴结转移呈正相关. FABP4 蛋白水平与E钙粘蛋白呈负相关 (r=−0.3292, P=0.0196), 与 SNAIL 蛋白呈正相关 (r=0.5856, P<0.0001).

方法

采用酶联免疫吸附试验 (ELISA) 检测了 2017 年 10 月至 2018 年 5 月 50 例大肠癌手术患者和 50 例健康对照者血浆 FABP4 的表达. 用 ImageJ 软件测量腹部 CT 扫描时 VFA 的含量. 免疫组化法检测结直肠癌及癌旁组织中 FABP4、 E-钙粘蛋白 (E-cadherin) 和 Snail 蛋白的表达水平.

结论

高 LPA 和 VFA 是大肠癌患者血浆 FABP4 升高的危险因素. 大肠癌组织中 FABP4 蛋白高表达与淋巴结转移密切相关. 大肠癌组织中 FABP4 水平与 E-cadherin 和 Snail 表达相关, 说明 FABP4 可能与上皮间充质转化 (EMT) 有关.

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Acknowledgments

This work was supported by the Science Foundation of Wuxi Health and Family Planning Commission (No. Z201713 to Min XIA), and the Special Project of Clinical Medicine of Nantong University (No. 2019JQ006 to Yan ZHANG), China.

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Affiliations

Authors

Contributions

Min XIA, Yan ZHANG, and Wenjia ZHANG conceived and designed the experiments. Yan ZHANG wrote and edited the manuscript. Yan ZHANG, Zhujun XIE, Wenying TIAN, and Tianyue ZHU performed the experiments. Yan ZHANG, Wenjia ZHANG, and Zhujun XIE analyzed the data. Min XIA, Fangmei AN, and Qiang ZHAN revised the manuscript. All authors have read and approved the fnal manuscript and, therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.

Corresponding author

Correspondence to Min Xia.

Ethics declarations

Yan ZHANG, Wenjia ZHANG, Min XIA, Zhujun XIE, Fangmei AN, Qiang ZHAN, Wenying TIAN, and Tianyue ZHU declare that they have no conflict of interest.

The present study was approved by the Ethics Committee of Wuxi People’s Hospital Affiliated to Nanjing Medical University (Wuxi, China) and with the Helsinki Declaration of 1975, as revised in 2008 (5). All the patients and volunteers provided written informed consent for participation in this study. Additional informed consent was obtained from all patients for which identifying information is included in this article.

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Zhang, Y., Zhang, W., Xia, M. et al. High expression of FABP4 in colorectal cancer and its clinical significance. J. Zhejiang Univ. Sci. B 22, 136–145 (2021). https://doi.org/10.1631/jzus.B2000366

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Key words

  • Fatty acid-binding protein 4 (FABP4)
  • Colorectal cancer (CRC)
  • Epithelial-mesenchymal transition

关键词

  • 脂肪酸结合蛋白4 (FABP4)
  • 结直肠癌 (CRC)
  • 上皮间充质转化