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The Expression of Glypican-3 in Colorectal Cancer

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Abstract—Glypican-3 (GPC3), a heparan sulfate proteoglycan is an emerging tumor marker; its overexpression has been stated in several types of cancer such as hepatocellular carcinoma (HCC), melanoma and etc. In this study, the expression of the GPC3 mRNA was investigated in 61 human colorectal cancer (CRC) tissues and 61 normal adjacent tissues, using the real-time PCR assay. Using immunohistochemistry (IHC), the expression of the GPC3 protein was examined in the cases that showed a marked elevation in the expression of the GPC3 mRNA in the tumor tissues, compared to the normal tissues. A significant increase in the expression of the GPC3 gene was revealed in 49.2% of the cases of CRC tumors, compared to the normal adjacent tissues. The expression of the GPC3 mRNA was found to significantly correlate with the pathological differentiation and the age of the patients. Interestingly, a significant reduction in the expression of the GPC3 mRNA was found in the tumor tissues of the 16 patients, who underwent the neoadjuvant chemotherapy, compared to the normal adjacent tissues. Unexpectedly, the GPC3 protein was not detected by IHC in 30 tissues, exhibiting the upregulation in the expression of the GPC3 mRNA. Our results indicated that GPC3 could be expressed in the CRC tissues at the mRNA level, while its expression could not be found at the protein level.

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REFERENCES

  1. Gervaz, P., Bouzourene, H., Cerottini, J.P., Chaubert, P., Benhattar, J., Secic, M., Wexner, S., Givel, J.C., and Belin, B., and Dukes, B., Colorectal cancer: distinct genetic categories and clinical outcome based on proximal or distal tumor location, Dis. Colon Rectum., 2001, vol. 44, no. 3, pp. 364–372.

    Article  CAS  Google Scholar 

  2. Terzic, J., Grivennikov, S., Karin, E., and Karin, M., Inflammation and colon cancer, Gastroenterology, 2010, vol. 138, no. 6, pp. 2101–2114. e5. https://doi.org/10.1053/j.gastro.2010.01.058

    Article  Google Scholar 

  3. Abdifard, E., Amini, S., Bab, S., Masroor, N., Khachian, A., and Heidari, M., Incidence trends of colorectal cancer in Iran during 2000–2009: a population-based study, Med. J. Islam. Repub. Iran, 2016, vol. 30, p. 382.

    PubMed  PubMed Central  Google Scholar 

  4. Center, M.M., Jemal, A., and Ward, E., International trends in colorectal cancer incidence rates, Cancer Epid. Prevent. Biomark., 2009, vol. 18, no. 6, pp. 1688–1694.

    Article  Google Scholar 

  5. Siegel, R.L., Miller, K.D., Fedewa, S.A., Ahnen, D.J., Meester, R.G.S., Barzi, A., and Jemal, A., Colorectal cancer statistics. 2017, CA Cancer J. Clin., 2017, vol. 67, no. 3, pp. 177–93. https://doi.org/10.3322/caac.21395

    Article  PubMed  Google Scholar 

  6. De Cat, B. and David, G., Developmental roles of the glypicans, Semin. Cell Dev. Biol., 2001, vol. 12, no. 2, pp. 117–125.https://doi.org/10.1006/scdb.2000.0240

    Article  CAS  PubMed  Google Scholar 

  7. Wang, X.Y., Degos, F., Dubois, S., Tessiore, S., Allegretta, M., Guttmann, R.D., Jothy, S., Belghiti, J., Bedossa, P., and Paradis, V., Glypican-3 expression in hepatocellular tumors: diagnostic value for preneoplastic lesions and hepatocellular carcinomas, Hum. Pathol., 2006, vol. 37, no. 11, pp. 1435–1441. https://doi.org/10.1016/j.humpath.2006.05.016

    Article  CAS  PubMed  Google Scholar 

  8. Traister, A., Shi, W., and Filmus, J., Mammalian Notum induces the release of glypicans and other GPI-anchored proteins from the cell surface, Biochem. J., 2008, vol. 410, no. 3, pp. 503–511.

    Article  CAS  Google Scholar 

  9. Ho, M. and Kim, H., Glypican-3: a new target for cancer immunotherapy, Eur. J. Cancer, 2011, vol. 47, no. 3, p. 333–338. https://doi.org/10.1016/j.ejca.2010.10.024

    Article  CAS  PubMed  Google Scholar 

  10. Pilia, G., Hughes-Benzi,e, R.M., MacKenzie, A., Baybayan, P., Chen, E.Y., Huber, R., Neri, G., Cao, A., Forabosco, A., and Schlessinger, D., Mutations in GPC3, a glypican gene, cause the Simpson–Golabi–Behmel overgrowth syndrome, Nat. Genet., 1996, vol. 12, no. 3, pp. 241–247. https://doi.org/10.1038/ng0396-241

    Article  CAS  PubMed  Google Scholar 

  11. Yun-Yan, X., Ladeda, V., and Filmus, J., Glypican-3 expression is silenced in human breast cancer, Oncogene, 2001, vol. 20, no. 50, pp. 7408–7412. https://doi.org/10.1038/sj.onc.1204925

    Article  CAS  Google Scholar 

  12. Capurro, M.I., Xu, P., Shi, W., Li, F., Jia, A., and Filmus, J., Glypican-3 inhibits Hedgehog signaling during development by competing with patched for Hedgehog binding, Dev. Cell, 2008, vol. 14, no. 5, pp. 700–711. https://doi.org/10.1016/j.devcel.2008.03.006

    Article  CAS  PubMed  Google Scholar 

  13. Capurro, M.I., Xiang, Y.Y., Lobe, C., and Filmus, J., Glypican-3 promotes the growth of hepatocellular carcinoma by stimulating canonical Wnt signaling, Cancer Res., 2005, vol. 65, no. 14, pp. 6245–6254. https://doi.org/10.1158/0008-5472.CAN-04-4244

    Article  CAS  PubMed  Google Scholar 

  14. Feng, M. and Ho, M., Glypican-3 antibodies: a new therapeutic target for liver cancer, FEBS Lett., 2014, vol. 588, no. 2, pp. 377–82. https://doi.org/10.1016/j.febslet.2013.10.002

    Article  CAS  PubMed  Google Scholar 

  15. Song, H.H., Shi, W., Xiang, Y.Y., and Filmus, J., The loss of glypican-3 induces alterations in Wnt signaling, J. Biol. Chem., 2005, vol. 280, no. 3, pp. 2116–2125. https://doi.org/10.1074/jbc.M410090200

    Article  CAS  PubMed  Google Scholar 

  16. Dwivedi, P., Lam, N., and Powell, B.C., Boning up on glypicans—opportunities for new insights into bone biology, Cell Biochem. Func., 2013, vol. 31, no. 2, pp. 91–114. https://doi.org/10.1002/cbf.2939

    Article  CAS  Google Scholar 

  17. Capurro, M., Martin, T., Shi, W., and Filmus, J., Glypican-3 binds to Frizzled and plays a direct role in the stimulation of canonical Wnt signaling, J. Cell Sci., 2014, vol. 127, no. 7, pp. 1565–1575. https://doi.org/10.1242/jcs.140871

    Article  CAS  PubMed  Google Scholar 

  18. Sun, C.K., Chua, M.S., He, J., and So, S.K., Suppression of glypican 3 inhibits growth of hepatocellular carcinoma cells through up-regulation of TGF-2, Neoplasia, 2011, vol. 13, no. 8, pp. 735–747. https://doi.org/10.1593/neo.11664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yamanaka, K., Ito, Y., Okuyama, N., Noda, K., Matsumoto, H., Yoshida, H., Miyauchi, A., Capurro, M., Filmus, J., and Miyoshi, E., Immunohistochemical study of glypican 3 in thyroid cancer, Oncology, 2007, vol. 73, nos. 5/6, pp. 389–94. https://doi.org/10.1159/000136159

    Article  CAS  PubMed  Google Scholar 

  20. Shirakawa, H., Kuronuma, T., Nishimura, Y., Hasebe, T., Nakano, M., Gotohda, N., Takahashi, S., Nakagohri, T., Konishi, M., Kobayashi, N., Kinoshita, T., and Nakatsura, T., Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer, Int. J. Oncol., 2009, vol. 34, no. 3, pp. 649–656. https://doi.org/10.3892/ijo_00000190

    Article  CAS  PubMed  Google Scholar 

  21. Nakatsura, T., Kageshita, T., Ito, S., Wakamatsu, K., Monji, M., Ikuta, Y., Senju, S., Ono, T., and Nishimura, Y., Identification of glypican-3 as a novel tumor marker for melanoma, Clin. Cancer Res., 2004, vol. 10, no. 19, p. 6612–6621. https://doi.org/10.1158/1078-0432.CCR-04-0348

    Article  CAS  PubMed  Google Scholar 

  22. Maeda, D., Ota, S., Takazawa, Y., Aburatani, H., Nakagawa, S., Yano, T., Taketani, Y., Kodama, T., and Fukayama, M., Glypican-3 expression in clear cell adenocarcinoma of the ovary, Mod. Pathol., 2009, vol. 22, no. 6, pp. 824–832. https://doi.org/10.1038/modpathol.2009.40

    Article  CAS  PubMed  Google Scholar 

  23. FFu, S.J., Qi, C.Y., Xiao, W.K., Li, S.Q., Peng, B.G., and Liang, L.J., Glypican-3 is a potential prognostic biomarker for hepatocellular carcinoma after curative resection, Surgery, 2013, vol. 154, no. 3, pp. 536–544. https://doi.org/10.1016/j.surg.2013.02.014

    Article  Google Scholar 

  24. van Diest, P.J., van Dam, P., Henzen-Logmans, S.C., Berns, E., van der Burg, M.E., Green, J., and Vergote, I., A scoring system for immunohistochemical staining: consensus report of the task force for basic research of the EORTC-GCCG. European Organization for Research and Treatment of Cancer-Gynaecological Cancer Cooperative Group, J. Clin. Pathol., 1997, vol. 50, no. 10, pp. 801–804. https://doi.org/10.1136/jcp.50.10.801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Umezu, T., Shibata, K., Kajiyama, H., Yamamoto, E., Nawa, A., and Kikkawa, F., Glypican-3 expression predicts poor clinical outcome of patients with early-stage clear cell carcinoma of the ovary, J. Clin. Pathol., 2010, vol. 63, no. 11, pp. 962–966. https://doi.org/10.1136/jcp.2010.080234

    Article  CAS  PubMed  Google Scholar 

  26. Kendrick, N., A Gene’s mRNA Level Does Not Usually Predict Its Protein Level, Madison: Kendricklabscom, 2014.

    Google Scholar 

  27. Schwanhausser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., and Selbach, M., Global quantification of mammalian gene expression control, Nature, 2011, vol. 473, pp. 337–342.

    Article  Google Scholar 

  28. Vogel, C., Abreu, Rde.S., Ko, D., Le, S.Y., Shapiro, B.A., Burns, S.C., Sandhu, D., Boutz, D.R., Marcotte, E.M., and Penalva, L.O., Sequence signatures and mRNA concentration can explain two-thirds of protein abundance variation in a human cell line, Mol. Syst. Biol., 2010, vol. 6, no. 1, p. 400. https://doi.org/10.1038/msb.2010.59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Asangani, I.A., Rasheed, S.A., Nikolova, D.A., Leupold, J.H., Colburn, N.H., Post, S., and Allgayer, H., microRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer, Oncogene, 2008, vol. 27, no. 15, pp. 2128–2136. https://doi.org/10.1038/sj.onc.1210856

    Article  CAS  PubMed  Google Scholar 

  30. Slaby, O., Svoboda, M., Michalek, J., and Vyzula, R., microRNAs in colorectal cancer: translation of molecular biology into clinical application, Mol. Cancer, 2009, vol. 8, no. 1, p. 102. https://doi.org/10.1186/1476-4598-8-102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Miao, H.L., Lei, C.J., Qiu, Z.D., Liu, Z.K., Li, R., Bao, S.T., and Li, M.Y., microRNA-520c-3p inhibits hepatocellular carcinoma cell proliferation and invasion through induction of cell apoptosis by targeting glypican-3, Hepatol. Res., 2014, vol. 44, no. 3, pp. 338–348. https://doi.org/10.1111/hepr.12121

    Article  CAS  PubMed  Google Scholar 

  32. Hay, E.D., Cell Biology of Extracellular Matrix, Springer Science and Business Media, 2013.

    Google Scholar 

  33. Joypaul, B.V., Newman, E.L., Hopwood, D., Grant, A., Qureshi, S., Lane, D.P., and Cuschieri, A., Expression of p53 protein in normal, dysplastic, and malignant gastric mucosa: an immunohistochemical study, J. Pathol., 1993, vol. 170, no. 3, pp. 279–283. https://doi.org/10.1002/path.1711700310

    Article  CAS  PubMed  Google Scholar 

  34. Yoneda, A., Lendorf, M.E., Couchman, J.R., and Multhaupt, H.A., Breast and ovarian cancers: a survey and possible roles for the cell surface heparan sulfate proteoglycans, J. Histochem. Cytochem., 2012, vol. 60, no. 1, pp. 9–21. https://doi.org/10.1369/0022155411428469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Araki, K. and Nagata, K., Protein folding and quality control in the ER, Cold Spring Harb. Perspect. Biol., 2011, vol. 3, no. 11, p. a007526. https://doi.org/10.1101/cshperspect.a007526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Montalbano, M., Georgiadis, J., Masterson, A.L., McGuire, J.T., Prajapati, J., Shirafkan, A., Rastellini, C., and Cicalese, L., Biology and function of glypican-3 as a candidate for early cancerous transformation of hepatocytes in hepatocellular carcinoma, Oncology Rep., 2017, vol. 37, no. 3, pp. 1291–1300. https://doi.org/10.3892/or.2017.5387

    Article  CAS  Google Scholar 

  37. Haggar, F.A. and Boushey, R.P., Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors, Clin. Colon Rect. Surg., 2009, vol. 22, no. 4, pp. 191–197. https://doi.org/10.1055/s-0029-1242458

    Article  Google Scholar 

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Authors and Affiliations

  1. Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Sonia Azizpour, Massoud Saidijam, Ali Mahdavinezhad, Hamid Eslami & Razieh Amini

  2. Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran

    Razieh Ezati

  3. Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran

    Amirnader Emami Razavi & Fatemeh Kamali

  4. Microbiology Department, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Farid Azizi Jalilian

  5. Modeling of Noncommunicable Disease Research Center, Department of Biostatistics, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran

    Alireza Soltanian

  6. Cancer Research Center, Cancer Institute of Iran, Tehran university of Medical Sciences, Tehran, Iran

    Hadiseh Mohammadpour

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  1. Sonia Azizpour
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Azizpour, S., Ezati, R., Saidijam, M. et al. The Expression of Glypican-3 in Colorectal Cancer. Cytol. Genet. 53, 430–440 (2019). https://doi.org/10.3103/S0095452719050037

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