中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 38 Issue 6
Jun.  2022
Turn off MathJax
Article Contents

Expression of calcitonin gene-related peptide-receptor component protein in hepatocellular carcinoma and its association with prognosis

DOI: 10.3969/j.issn.1001-5256.2022.06.021
Research funding:

National Natural Science Foundation of China (81801570);

Youth Fund Project of Shanghai Municipal Health Commission (20194Y0269);

Shanghai Sailing Project from the Science and Technology Commission of Shanghai Municipality (20YF1459600)

More Information
  • Corresponding author: CHENG Zhuo, chengzhuo1219@163.com (ORCID:0000-0002-2967-3167)
  • Received Date: 2021-11-01
  • Accepted Date: 2022-01-27
  • Published Date: 2022-06-20
  •   Objective  To investigate the expression level of calcitonin gene-related peptide-receptor component protein (CRCP) in hepatocellular carcinoma (HCC) tissue and adjacent tissue and its association with the clinicopathological features and prognosis of patients.  Methods  HCC and adjacent tissue samples were collected from 79 HCC patients who underwent surgical resection in Eastern Hepatobiliary Surgery Hospital, Navy Medical University, from June 2003 to September 2009. Tissue microarray was prepared, and immunohistochemistry was used for quantitative analysis. Related proteins were extracted and measured by Western blot, and the expression of CRCP was compared between HCC tissue and adjacent tissue. The chi-square test was used for comparison of categorical data between groups. The receiver operating characteristic (ROC) curve analysis was performed to obtain the area under the ROC curve (AUC), and goodness of fit was evaluated. Youden index was used to determine the optimal cut-off value. and the Kaplan-Meier survival analysis was used to analyze the association of CRCP expression with the recurrence and prognosis of HCC, and the log rank test was used for comparison between the two groups.  Results  Among the 79 HCC patients, there were 67 male patients and 12 female patients, with an age of 10-72 years, and 20 patients had portal vein tumor thrombus. As for pathological grade, 1 had grade 4 HCC, 61 had grade 3 HCC, and 17 had grade 2 HCC; as for BCLC stage, 5 had BCLC stage 0 HCC, 55 had BCLC stage A HCC, 11 had BCLC stage B HCC, and 8 had BCLC stage C HCC. Western blot showed that the expression level of CRCP in HCC tissue was lower than that in adjacent tissue in 4 patients, and immunohistochemistry showed that the expression level of CRCP in HCC tissue was significantly lower than that in adjacent tissue in 75.9% of the patients. Low CRCP expression was associated with CK19 positivity, incomplete tumor capsule, presence of portal vein tumor thrombus, and high pathological grade (χ2=6.410, 4.829, 9.319, and 9.083, all P < 0.05). Compared with the low CRCP expression group, the high CRCP expression group had a significantly longer overall survival time and a significantly lower recurrence rate (P < 0.001 and P=0.009).  Conclusion  Patients with low CRCP expression in HCC tissue tend to have a poorer prognosis than those with high CRCP expression, and CRCP may participate in the development, progression, and metastasis of HCC, suggesting that this molecule can be used as a potential biomarker to predict the prognosis of HCC patients.

     

  • loading
  • [1]
    DAMIRIS K, ABBAD H, PYRSOPOULOS N. Cellular based treatment modalities for unresectable hepatocellular carcinoma[J]. World J Clin Oncol, 2021, 12(5): 290-308. DOI: 10.5306/wjco.v12.i5.290.
    [2]
    JEMAL A, WARD EM, JOHNSON CJ, et al. Annual report to the nation on the status of cancer, 1975-2014, featuring survival[J]. J Natl Cancer Inst, 2017, 109(9): djx030. DOI: 10.1093/jnci/djx030.
    [3]
    World Health Organization. Projections of mortality and causes of death, 2016 to 2060[EB/OL]. https://www.who.int/healthinfo/global_burden_disease/projections_method.pdf?ua=1.
    [4]
    SCHEAU C, DRAGHICI C, ILIE MA, et al. Neuroendocrine factors in melanoma pathogenesis[J]. Cancers (Basel), 2021, 13(9): 2277. DOI: 10.3390/cancers13092277.
    [5]
    ZABEL M, DIETEL M, GEBAROWSKA E, et al. Effect of follicular cells on calcitonin gene expression in thyroid parafollicular cells in cell culture[J]. Histochem J, 1999, 31(3): 175-180. DOI: 10.1023/a:1003597416140.
    [6]
    HOU KS, WANG LL, WANG HB, et al. Progress in the study of calcitonin gene-related peptide receptor[J]. Prog Physiol Sci, 2019, 50(5): 396-401, e1. DOI: 10.3969/j.issn.0559-7765.2019.05.017.

    侯可赛, 王林林, 王洪波, 等. 降钙素基因相关肽受体研究的新进展[J]. 生理科学进展, 2019, 50(5): 396-401, e1. DOI: 10.3969/j.issn.0559-7765.2019.05.017.
    [7]
    GAO HM, YANG SY. Research progress of tumor amino acid metabolism[J]. Med & Pharm J Chin PLA, 2021, 33(8): 112-116. DOI: 10.3969/j.issn.2095-140X.2021.08.025.

    高红梅, 杨仕仪. 肿瘤氨基酸代谢研究进展[J]. 解放军医药杂志, 2021, 33(8): 112-116. DOI: 10.3969/j.issn.2095-140X.2021.08.025.
    [8]
    FIDLER IJ. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited[J]. Nat Rev Cancer, 2003, 3(6): 453-458. DOI: 10.1038/nrc1098.
    [9]
    WANG T, CHEN DF. Clinical diagnosis and treatment of hepatocellular carcinoma: From guidelines to clinical practice[J]. J Clin Hepatol, 2021, 37(8): 1745-1747. DOI: 10.3969/j.issn.1001-5256.2021.08.001.

    王涛, 陈东风. 肝细胞癌的临床诊治: 从指南到临床实践[J]. 临床肝胆病杂志, 2021, 37(8): 1745-1747. DOI: 10.3969/j.issn.1001-5256.2021.08.001.
    [10]
    HUAMAN J, BACH C, ILBOUDO A, et al. Epithelial-to-mesenchymal transition in hepatocellular carcinoma[M]. Germany, Cham: Springer, 2018.
    [11]
    AMARA SG, JONAS V, ROSENFELD MG, et al. Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products[J]. Nature, 1982, 298(5871): 240-244. DOI: 10.1038/298240a0.
    [12]
    MULDERRY PK, GHATEI MA, RODRIGO J, et al. Calcitonin gene-related peptide in cardiovascular tissues of the rat[J]. Neuroscience, 1985, 14(3): 947-954. DOI: 10.1016/0306-4522(85)90156-3.
    [13]
    BRAIN SD, WILLIAMS TJ, TIPPINS JR, et al. Calcitonin gene-related peptide is a potent vasodilator[J]. Nature, 1985, 313(5997): 54-56. DOI: 10.1038/313054a0.
    [14]
    OKAMOTO H, HOKA S, KAWASAKI T, et al. Effects of CGRP on baroreflex control of heart rate and renal sympathetic nerve activity in rabbits[J]. Am J Physiol, 1992, 263(4 Pt 2): R874-R879. DOI: 10.1152/ajpregu.1992.263.4.R874.
    [15]
    TOLUN AA, DICKERSON IM, MALHOTRA A. Overexpression and purification of human calcitonin gene-related peptide-receptor component protein in Escherichia coli[J]. Protein Expr Purif, 2007, 52(1): 167-174. DOI: 10.1016/j.pep.2006.09.008.
    [16]
    PRADO MA, EVANS-BAIN B, OLIVER KR, et al. The role of the CGRP-receptor component protein (RCP) in adrenomedullin receptor signal transduction[J]. Peptides, 2001, 22(11): 1773-1781. DOI: 10.1016/s0196-9781(01)00517-4.
    [17]
    MA W, CHABOT JG, POWELL KJ, et al. Localization and modulation of calcitonin gene-related peptide-receptor component protein-immunoreactive cells in the rat central and peripheral nervous systems[J]. Neuroscience, 2003, 120(3): 677-694. DOI: 10.1016/s0306-4522(03)00159-3.
    [18]
    WEI YL, XU J, ZHANG WQ, et al. RNA polymerase Ⅲ component Rpc9 regulates hematopoietic stem and progenitor cell maintenance in zebrafish[J]. Development, 2016, 143(12): 2103-2110. DOI: 10.1242/dev.126797.
    [19]
    GAO F, LIU G, WANG J, et al. Methylation of CALCA and CALCB in pancreatic ductal adenocarcinoma[J]. Oxid Med Cell Longev, 2021, 2021: 2088345. DOI: 10.1155/2021/2088345.
    [20]
    LIU YM, PENG HY, GUO F, et al. Involvement of the receptor component protein in the regulation of vascular peroxidase-1 expression induced by calcitonin gene-related peptide and angiotensin Ⅱ in vascular smooth muscle cell[J]. Acta Physiologica Sin, 2015, 67(2): 193-200. DOI: 10.13294/j.aps.2015.0023.

    刘彦梅, 彭虹艳, 郭锋, 等. 受体成分蛋白在降钙素基因相关肽和血管紧张素Ⅰ对血管平滑肌细胞血管过氧化物酶1表达调控中的作用[J]. 生理学报, 2015, 67(2): 193-200. DOI: 10.13294/j.aps.2015.0023.
    [21]
    LI ZF, XIAO N, YAO JX, et al. Role of microRNA-34a in epithelial-mesenchymal transition[J]. Clin Misdiagn Misther, 2020, 33(7): 109-113. DOI: 10.3969/j.issn.1002-3429.2020.07.026.

    李占峰, 肖楠, 姚建新, 等. microRNA-34a在上皮-间充质转化中的作用[J]. 临床误诊误治, 2020, 33(7): 109-113. DOI: 10.3969/j.issn.1002-3429.2020.07.026.
    [22]
    LOU W, CHEN J, DING B, et al. Identification of invasion-metastasis-associated microRNAs in hepatocellular carcinoma based on bioinformatic analysis and experimental validation[J]. J Transl Med, 2018, 16(1): 266. DOI: 10.1186/s12967-018-1639-8.
    [23]
    FENG J, ZHU R, CHANG C, et al. CK19 and Glypican 3 expression profiling in the prognostic indication for patients with HCC after surgical resection[J]. PLoS One, 2016, 11(3): e0151501. DOI: 10.1371/journal.pone.0151501.
    [24]
    YAMAMOTO T, UENISHI T, OGAWA M, et al. Immunohistologic attempt to find carcinogenesis from hepatic progenitor cell in hepatocellular carcinoma[J]. Dig Surg, 2005, 22(5): 364-370. DOI: 10.1159/000090515.
    [25]
    LEE CW, KUO WL, YU MC, et al. The expression of cytokeratin 19 in lymph nodes was a poor prognostic factor for hepatocellular carcinoma after hepatic resection[J]. World J Surg Oncol, 2013, 11(1): 136. DOI: 10.1186/1477-7819-11-136.
    [26]
    YONEDA N, SATO Y, KITAO A, et al. Epidermal growth factor induces cytokeratin 19 expression accompanied by increased growth abilities in human hepatocellular carcinoma[J]. Lab Invest, 2011, 91(2): 262-272. DOI: 10.1038/labinvest.2010.161.
    [27]
    HOSHIDA Y, TOFFANIN S, LACHENMAYER A, et al. Molecular classification and novel targets in hepatocellular carcinoma: recent advancements[J]. Semin Liver Dis, 2010, 30(1): 35-51. DOI: 10.1055/s-0030-1247131.
    [28]
    ZHONG F. Expression and significance of cytokeratin 19 in hepatocellular carcinoma[D]. Guangzhou: Sun Yat-sen University, 2006.

    钟锋. CK19表达在肝细胞性肝癌中的意义[D]. 广州: 中山大学, 2006.
    [29]
    LIU YA, LIU FY, ZHANG EL, et al. Clinicopathologic features of hepatocellular carcinoma without fibrous capsule and the postoperative prognostic analysis[J]. Acta Med Univ Sci Technol Huazhong, 2013, 42(5): 592-596. DOI: 10.3870/j.issn. 1672-0741.2013.05.020.

    刘杨安, 刘富瑶, 张二雷, 等. 无肿瘤包膜的肝细胞癌临床病理特征及术后预后分析[J]. 华中科技大学学报(医学版), 2013, 42(5): 592-596. DOI: 10.3870/j.issn. 1672-0741.2013.05.020.
  • 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(3)  / Tables(1)

    Article Metrics

    Article views (459) PDF downloads(42) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return