Similar articles

Abstract: ObjectiveTo investigate the relationship between the fatty acid-binding protein 4 (FABP4) and colorectal cancer (CRC).
MethodsUsing 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.
ResultsThe 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).
ConclusionsHigh 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).

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

[1]Furuhashi M, Saitoh S, Shimamoto K, et al., 2014. Fatty acid-binding protein 4 (FABP4): pathophysiological insights and potent clinical biomarker of metabolic and cardiovascular diseases. Clin Med Insights Cardiol, 8(S3):23-33.

[2]Gan L, Liu ZJ, Cao WN, et al., 2015. FABP4 reversed the regulation of leptin on mitochondrial fatty acid oxidation in mice adipocytes. Sci Rep, 5:13588.

[3]Gao XC, 2013. The Effect and Mechanism of Lysophosphatidic Acid Oil Metastasis and Anti-apoptosis in Colorectal Carcinoma. MS Thesis, Guangzhou Medical University, Guangzhou, China (in Chinese).

[4]Guaita-Esteruelas S, Saavedra-García P, Bosquet A, et al., 2017. Adipose-derived fatty acid-binding proteins plasma concentrations are increased in breast cancer patients. Oncologist, 22(11):1309-1315.

[5]Jin JB, Zhang ZY, Zhang S, et al., 2018. Fatty acid binding protein 4 promotes epithelial-mesenchymal transition in cervical squamous cell carcinoma through AKT/GSK3β/Snail signaling pathway. Mol Cell Endocrinol, 461:155-164.

[6]Kooijman EE, Chupin V, Kruijff BD, et al., 2010. Modulation of membrane curvature by phosphatidic acid and lysophosphatidic acid. Traffic, 4(3):162-174.

[7]Lee H, Song MY, Shin N, et al., 2012. Diagnostic significance of serum HMGB1 in colorectal carcinomas. PLoS ONE, 7(4):e34318.

[8]Li H, Chen YX, Wen JG, et al., 2017. Metastasis-associated in colon cancer 1: a promising biomarker for the metastasis and prognosis of colorectal cancer (Review). Oncol Lett, 14(4):3899-3908.

[9]Liesenfeld DB, Grapov D, Fahrmann JF, et al., 2015. Metabolomics and transcriptomics identify pathway differences between visceral and subcutaneous adipose tissue in colorectal cancer patients: the ColoCare study. Am J Clin Nutr, 102(2):433-443.

[10]Mathis C, Lascombe I, Monnien F, et al., 2018. Down-regulation of A-FABP predicts non-muscle invasive bladder cancer progression: investigation with a long term clinical follow-up. BMC Cancer, 18:1239.

[11]Miller KD, Nogueira L, Mariotto AB, et al., 2019. Cancer treatment and survivorship statistics, 2019. CA: A Cancer J Clin, 69(5):363-385.

[12]Moriarity A, O'Sullivan J, Kennedy J, et al., 2016. Current targeted therapies in the treatment of advanced colorectal cancer: a review. Ther Adv Med Oncol, 8(4):276-293.

[13]Nam SY, Kim BC, Han KS, et al., 2010. Abdominal visceral adipose tissue predicts risk of colorectal adenoma in both sexes. Clin Gastroenterol Hepatol, 8(5):443-450.e2.

[14]Nie J, Zhang J, Wang L, et al., 2017. Adipocytes promote cholangiocarcinoma metastasis through fatty acid binding protein 4. J Exp Clin Cancer Res, 36:183.

[15]Nieman KM, Kenny HA, Penicka CV, et al., 2011. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med, 17(11):1498-1503.

[16]Tang ZY, Shen Q, Xie H, et al., 2016. Elevated expression of FABP3 and FABP4 cooperatively correlates with poor prognosis in non-small cell lung cancer (NSCLC). Oncotarget, 7(29 ): 46253-46262.

[17]Uehara H, Takahashi T, Oha M, et al., 2014. Exogenous fatty acid binding protein 4 promotes human prostate cancer cell progression. Int J Cancer, 135(11):2558-2568.

[18]Wan XH, Guo DR, Zhu Q, et al., 2020. MicroRNA-382 suppresses the progression of pancreatic cancer through the PI3K/Akt signaling pathway by inhibition of Anxa3. Am J Physiol-Gastrointest Liver Physiol, 319(3):G309-G322.

[19]Wang J, 2017. Association Between Serum Lipid, FABP4 and Colorectal Carcinoma. MS Thesis, Nanjing University of Chinese Medicine, Nanjing, China (in Chinese).

[20]Zhang YQ, Zhao XT, Deng LL, et al., 2019. High expression of FABP4 and FABP6 in patients with colorectal cancer. World J Surg Oncol, 17(1):171.

[21]Zheng M, Jiang YP, Chen W, et al., 2015. Snail and slug collaborate on EMT and tumor metastasis through miR-101-mediated EZH2 axis in oral tongue squamous cell carcinoma. Oncotarget, 6(9):6794-6810.

[22]Zhong CQ, Zhang XP, Ma N, et al., 2018. FABP4 suppresses proliferation and invasion of hepatocellular carcinoma cells and predicts a poor prognosis for hepatocellular carcinoma. Cancer Med, 7(6):2629-2640.