Full Text:   <1094>

Summary:  <1117>

CLC number: 

On-line Access: 2021-02-07

Received: 2020-07-14

Revision Accepted: 2020-10-29

Crosschecked: 2021-01-18

Cited: 0

Clicked: 1849

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Min XIA

https://orcid.org/0000-0002-6394-9294

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2021 Vol.22 No.2 P.136-145

http://doi.org/10.1631/jzus.B2000366


High expression of FABP4 in colorectal cancer and its clinical significance


Author(s):  Yan ZHANG, Wenjia ZHANG, Min XIA, Zhujun XIE, Fangmei AN, Qiang ZHAN, Wenying TIAN, Tianyue ZHU

Affiliation(s):  Department of Gastroenterology, the Second Affiliated Hospital of Nantong University, Nantong 226001, China; more

Corresponding email(s):   xmzb1013@163.com

Key Words:  Fatty acid-binding protein 4 (FABP4), Colorectal cancer (CRC), Epithelial-mesenchymal transition


Yan ZHANG, Wenjia ZHANG, Min XIA, Zhujun XIE, Fangmei AN, Qiang ZHAN, Wenying TIAN, Tianyue ZHU. High expression of FABP4 in colorectal cancer and its clinical significance[J]. Journal of Zhejiang University Science B, 2021, 22(2): 136-145.

@article{title="High expression of FABP4 in colorectal cancer and its clinical significance",
author="Yan ZHANG, Wenjia ZHANG, Min XIA, Zhujun XIE, Fangmei AN, Qiang ZHAN, Wenying TIAN, Tianyue ZHU",
journal="Journal of Zhejiang University Science B",
volume="22",
number="2",
pages="136-145",
year="2021",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2000366"
}

%0 Journal Article
%T High expression of FABP4 in colorectal cancer and its clinical significance
%A Yan ZHANG
%A Wenjia ZHANG
%A Min XIA
%A Zhujun XIE
%A Fangmei AN
%A Qiang ZHAN
%A Wenying TIAN
%A Tianyue ZHU
%J Journal of Zhejiang University SCIENCE B
%V 22
%N 2
%P 136-145
%@ 1673-1581
%D 2021
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2000366

TY - JOUR
T1 - High expression of FABP4 in colorectal cancer and its clinical significance
A1 - Yan ZHANG
A1 - Wenjia ZHANG
A1 - Min XIA
A1 - Zhujun XIE
A1 - Fangmei AN
A1 - Qiang ZHAN
A1 - Wenying TIAN
A1 - Tianyue ZHU
J0 - Journal of Zhejiang University Science B
VL - 22
IS - 2
SP - 136
EP - 145
%@ 1673-1581
Y1 - 2021
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2000366


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

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(22.46ng/mL vs.9.82ng/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。

关键词:脂肪酸结合蛋白4(FABP4);结直肠癌(CRC);上皮间充质转化

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[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.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2022 Journal of Zhejiang University-SCIENCE