中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 6
Jun.  2021
Turn off MathJax
Article Contents

Serum expression of angiopoietin-like protein 2 in pancreatic cancer patients with or without diabetes and its association with prognosis

DOI: 10.3969/j.issn.1001-5256.2021.06.034
  • Received Date: 2021-02-02
  • Accepted Date: 2021-03-15
  • Published Date: 2021-06-20
  •   Objective  To investigate the expression level of angiopoietin-like protein 2 (ANGPTL2) in pancreatic cancer patients with or without diabetes and the clinical value of ANGPTL2 as a prognostic marker in patients with pancreatic cancer.  Methods  Serum samples were collected from 125 pancreatic cancer patients who were treated in The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University Cancer Hospital, and Wuming Hospital of Guangxi Medical University from January 2015 to January 2018, among whom 64 had pancreatic cancer alone and 61 had pancreatic cancer and diabetes, and 66 individuals who underwent physical examination were enrolled as control group. ELISA was used to measure the serum level of ANGPTL2, and the association of the expression level of ANGPTL2 with clinical indices, survival, and prognosis was analyzed. A one-way analysis of variance was used for comparison of normally distributed continuous data between three groups, and the Bonferroni test was used for comparison between two groups. The independent-samples Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between three groups and the one-way ANOVA analysis was used for comparison between two groups. The chi-square test was used for comparison of categorical data between groups. Spearman correlation analysis was also performed to investigate correlation. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison of survival rate. The Cox risk model was used to perform univariate and multivariate analyses to determine independent risk factors for the prognosis of pancreatic cancer.  Results  The pancreatic cancer+diabetes group had a significantly higher serum concentration of ANGPTL2 than the pancreatic cancer group and the control group [7.79 (7.12-8.17) ng/ml vs 5.74 (5.08-6.40) ng/ml and 3.72 (3.25-4.16) ng/ml, χ2=126.367, P < 0.001]. Serum ANGPTL2 concentration was positively correlated with carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) (r=0.560 and 0.731, both P < 0.001). The univariate analysis showed that tumor size, distant organ metastasis, degree of tumor differentiation, CEA, ANGPTL2, and HbA1c were closely associated with the long-term survival of pancreatic cancer patients, and the multivariate analysis showed that tumor size (HR=2.657, P=0.005), distant organ metastasis (HR=5.000, P=0.014), degree of tumor differentiation (HR=2.466, P=0.004), CEA(HR=1.110, P < 0.001) and ANGPTL2(HR=1.901, P=0.001) were independent risk factors for the prognosis of pancreatic cancer patients. For all pancreatic cancer patients, the high ANGPTL2 expression group had a significantly lower 2-year survival rate than the low ANGPTL2 expression group (8.51% vs 25.81%, χ2=5.651, P=0.017). For the pancreatic cancer patients with diabetes, the high ANGPTL2 expression group had a significantly lower 2-year survival rate than the low ANGPTL2 expression group (2.20% vs 32.70%, χ2=24.895, P < 0.001).  Conclusion  ANGPTL2 can be used as an effective clinical index to evaluate the prognosis of pancreatic cancer patients, especially those with diabetes.

     

  • loading
  • [1]
    ANTOLINO L, ROCCA M, TODDE F, et al. Can pancreatic cancer be detected by adrenomedullin in patients with new-onset diabetes? The PaCANOD cohort study protocol[J]. Tumori, 2018, 104(4): 312-314. DOI: 10.5301/tj.5000693.
    [2]
    ZHANG Z, QIN W, SUN Y. Contribution of biomarkers for pancreatic cancer-associated new-onset diabetes to pancreatic cancer screening[J]. Pathol Res Pract, 2018, 214(12): 1923-1928. DOI: 10.1016/j.prp.2018.10.003.
    [3]
    RISCH HA. Diabetes and pancreatic cancer: Both cause and effect[J]. J Natl Cancer Inst, 2019, 111(1): 1-2. DOI: 10.1093/jnci/djy093.
    [4]
    KADOMATSU T, ENDO M, MIYATA K, et al. Diverse roles of ANGPTL2 in physiology and pathophysiology[J]. Trends Endocrinol Metab, 2014, 25(5): 245-254. DOI: 10.1016/j.tem.2014.03.012.
    [5]
    KIM I, KWAK HJ, AHN JE, et al. Molecular cloning and characterization of a novel angiopoietin family protein, angiopoietin-3[J]. FEBS Lett, 1999, 443(3): 353-356. DOI: 10.1016/s0014-5793(99)00008-3.
    [6]
    KENAWY MZ, SABRY JH, AKL EM, et al. Angiopoietin-like protein 2 in psoriasis: A new linkage with metabolic syndrome[J]. Postepy Dermatol Alergol, 2020, 37(1): 86-91. DOI: 10.5114/ada.2018.79225.
    [7]
    WANG X, HU Z, WANG Z, et al. Angiopoietin-like protein 2 is an important facilitator of tumor proliferation, metastasis, angiogenesis and glycolysis in osteosarcoma[J]. Am J Transl Res, 2019, 11(10): 6341-6355. http://www.ncbi.nlm.nih.gov/pubmed/31737187
    [8]
    HE J, XU J, YU X, et al. Overexpression of ANGPTL2 and LILRB2 as predictive and therapeutic biomarkers for metastasis and prognosis in colorectal cancer[J]. Int J Clin Exp Pathol, 2018, 11(5): 2281-2294. http://www.ncbi.nlm.nih.gov/pubmed/31938340
    [9]
    ABBASZADEH Z, ÇEŞMELI S, BIRAY AÇ. Crucial players in glycolysis: Cancer progress[J]. Gene, 2020, 726: 144158. DOI: 10.1016/j.gene.2019.144158.
    [10]
    YOSHINAGA T, NIOU T, NⅡHARA T, et al. Angiopoietin-like protein 2 is a useful biomarker for pancreatic cancer that is associated with type 2 diabetes mellitus and inflammation[J]. J Cancer, 2018, 9(24): 4736-4741. DOI: 10.7150/jca.25404.
    [11]
    WANG Y, ZHENG Z, YANG Y, et al. Angiopoietin-like 2 is a potential biomarker for diabetic foot patients[J]. BMC Endocr Disord, 2020, 20(1): 178. DOI: 10.1186/s12902-020-00657-7.
    [12]
    BOURSI B, FINKELMAN B, GIANTONIO BJ, et al. A clinical prediction model to assess risk for pancreatic cancer among patients with prediabetes[J]. Eur J Gastroenterol Hepatol, 2021. DOI: 10.1097/MEG.0000000000002052.[Online ahead of print]
    [13]
    ANDERSEN DK, KORC M, PETERSEN GM, et al. Diabetes, pancreatogenic diabetes, and pancreatic cancer[J]. Diabetes, 2017, 66(5): 1103-1110. DOI: 10.2337/db16-1477.
    [14]
    PIZZATO M, TURATI F, ROSATO V, et al. Exploring the link between diabetes and pancreatic cancer[J]. Expert Rev Anticancer Ther, 2019, 19(8): 681-687. DOI: 10.1080/14737140.2019.1642109.
    [15]
    TABATA M, KADOMATSU T, FUKUHARA S, et al. Angiopoietin-like protein 2 promotes chronic adipose tissue inflammation and obesity-related systemic insulin resistance[J]. Cell Metab, 2009, 10(3): 178-188. DOI: 10.1016/j.cmet.2009.08.003.
    [16]
    FARHAT N, THORIN-TRESCASES N, MAMARBACHI M, et al. Angiopoietin-like 2 promotes atherogenesis in mice[J]. J Am Heart Assoc, 2013, 2(3): e000201. DOI: 10.1161/JAHA.113.000201.
    [17]
    TAZUME H, MIYATA K, TIAN Z, et al. Macrophage-derived angiopoietin-like protein 2 accelerates development of abdominal aortic aneurysm[J]. Arterioscler Thromb Vasc Biol, 2012, 32(6): 1400-1409. DOI: 10.1161/ATVBAHA.112.247866.
    [18]
    OGATA A, ENDO M, AOI J, et al. The role of angiopoietin-like protein 2 in pathogenesis of dermatomyositis[J]. Biochem Biophys Res Commun, 2012, 418(3): 494-499. DOI: 10.1016/j.bbrc.2012.01.052.
    [19]
    ENDO M, NAKANO M, KADOMATSU T, et al. Tumor cell-derived angiopoietin-like protein ANGPTL2 is a critical driver of metastasis[J]. Cancer Res, 2012, 72(7): 1784-1794. DOI: 10.1158/0008-5472.CAN-11-3878.
    [20]
    CHEN Y, JIANG H, ZHU L, et al. Diagnostic and prognostic value of serum angiopoietin-like protein 2 in patients with non-small cell lung cancer[J]. Clin Lab, 2017, 63(1): 59-65. DOI: 10.7754/Clin.Lab.2016.160528.
    [21]
    OSUMI H, HORIGUCHI H, KADOMATSU T, et al. Tumor cell-derived angiopoietin-like protein 2 establishes a preference for glycolytic metabolism in lung cancer cells[J]. Cancer Sci, 2020, 111(4): 1241-1253. DOI: 10.1111/cas.14337.
    [22]
    YANG L, SUN R, WANG Y, et al. Expression of ANGPTL2 and its impact on papillary thyroid cancer[J]. Cancer Cell Int, 2019, 19: 204. DOI: 10.1186/s12935-019-0908-9.
    [23]
    YOSHINAGA T, NISHIMATA H, TANAKA S, et al. Use of ANGPTL2 mRNA levels in formalin-fixed paraffin-embedded tissues as a biomarker to diagnose gastric cancer and to evaluate the extent of vascular invasion[J]. Oncol Lett, 2019, 17(1): 518-524. DOI: 10.3892/ol.2018.9610.
    [24]
    HUANG D, SUN G, HAO X, et al. ANGPTL2-containing small extracellular vesicles from vascular endothelial cells accelerate leukemia progression[J]. J Clin Invest, 2021, 131(1): e138986. DOI: 10.1172/JCI138986.
    [25]
    CARBONE C, MOCCIA T, ZHU C, et al. Anti-VEGF treatment-resistant pancreatic cancers secrete proinflammatory factors that contribute to malignant progression by inducing an EMT cell phenotype[J]. Clin Cancer Res, 2011, 17(17): 5822-5832. DOI: 10.1158/1078-0432.CCR-11-1185.
    [26]
    CARBONE C, PIRO G, FASSAN M, et al. An angiopoietin-like protein 2 autocrine signaling promotes EMT during pancreatic ductal carcinogenesis[J]. Oncotarget, 2015, 6(15): 13822-13834. DOI: 10.18632/oncotarget.2635.
    [27]
    CHEN H, LI T, WANG ZJ, et al. Influence of metabolic syndrome and its components on the prognosis of patients with pancreatic cancer[J]. J Clin Hepatol, 2020, 36(12): 2788-2794. DOI: 10.3969/j.issn.1001-5256.2020.12.029.

    陈欢, 李婷, 王紫洁, 等. 代谢综合征及其组分对胰腺癌患者预后的影响[J]. 临床肝胆病杂志, 2020, 36(12): 2788-2794. DOI: 10.3969/j.issn.1001-5256.2020.12.029.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(4)  / Tables(5)

    Article Metrics

    Article views (377) PDF downloads(16) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return