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Membrane Proteins as Potential Colon Cancer Biomarkers: Verification of 4 Candidates from a Secretome Dataset

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http://www.scirp.org/journal/PaperInformation.aspx?PaperID=50388#.VDy_fVfHRK0

Colorectal cancer (CRC) is an important health issue in Taiwan. There were over ten thousand newly diagnosed CRC patients each year. The outcome of late stage CRC still remains to be improved, and tumor markers are expected to improve CRC detection and management. From a colorectal cancer cell secretome database, we chose four proteins as candidates for clinical verification, including tumor-associated calcium signal transducer 2 (TROP2, TACSTD2), transmembrane 9 superfamily member 2 (TM9SF2), and tetraspanin-6 (TSPAN6), and tumor necrosis factor receptor superfamily member 16 (NGFR). Different groups of 30 CRC patients’ tissue samples collected from Chang Gung Memorial Hospital were analyzed by immunohistochemistry (IHC) for the four proteins, and the results were scored by pathologist. For all the four candidate proteins, marked differences of IHC score existed between tumor and adjacent non-tumor counterpart. However, there were only trends between higher protein expression levels and worse outcome. Three proteins (TROP2, TM9SF2 and NGFR) had trends between higher tissue expression and tumor stage or lymph node metastasis. Our study revealed that tissue expression of four proteins (TROP2, TM9SF2, TSPAN6, and NGFR) was markedly different between tumor and adjacent non-tumor counterparts. Overexpression of all these four proteins showed some trends with poorer survival.
Cite this paper
Chiang, S. , Tsai, M. , Tang, R. , Hsieh, L. , Chiang, J. , Yeh, C. , Hsieh, P. , Tsai, W. , Liu, Y. , Liang, Y. , Chen, J. and Yu, J. (2014) Membrane Proteins as Potential Colon Cancer Biomarkers: Verification of 4 Candidates from a Secretome Dataset. Surgical Science, 5, 418-438. doi: 10.4236/ss.2014.510067. 
 

[1] Health Promotion Administration, Ministry of Health and Welfare, Taiwan, R.O.C.
http://www.hpa.gov.tw/BHPNet/Web/Index/Index.aspx
[2] Hyodo, I., Suzuki, H., Takahashi, K., et al. (2010) Present Status and Perspectives of Colorectal Cancer in Asia: Colorectal Cancer Working Group Report in 30th Asia-Pacific Cancer Conference. Japanese Journal of Clinical Oncology, 40, i38-i43. http://dx.doi.org/10.1093/jjco/hyq125
[3] Tanzer, M., Liebl, M. and Quante, M. (2013) Molecular Biomarkers in Esophageal, Gastric, and Colorectal Adenocarcinoma. Pharmacology & Therapeutics, 140, 133-147.
http://dx.doi.org/10.1016/j.pharmthera.2013.06.005
[4] Luo, Y., Wang, L. and Wang, J. (2013) Developing Proteomics-Based Biomarkers for Colorectal Neoplasms for Clinical Practice: Opportunities and Challenges. PROTEOMICS—Clinical Applications, 7, 30-41.
http://dx.doi.org/10.1002/prca.201200071
[5] de Wit, M., Fijneman, R.J., Verheul, H.M., Meijer, G.A. and Jimenez, C.R. (2013) Proteomics in Colorectal Cancer Translational Research: Biomarker Discovery for Clinical Applications. Clinical Biochemistry, 46, 466-479. http://dx.doi.org/10.1016/j.clinbiochem.2012.10.039
[6] Manne, U., Shanmugam, C., Katkoori, V.R., Bumpers, H.L. and Grizzle, W.E. (2010) Development and Progression of Colorectal Neoplasia. Cancer Biomarks, 9, 235-265.
[7] Duffy, M.J., van Dalen, A., Haglund, C., et al. (2007) Tumour Markers in Colorectal Cancer: European Group on Tumour Markers (EGTM) Guidelines for Clinical Use. European Journal of Cancer, 43, 1348-1360. http://dx.doi.org/10.1016/j.ejca.2007.03.021
[8] Wang, J.Y., Tang, R. and Chiang, J.M. (1994) Value of Carcinoembryonic Antigen in the Management of Colorectal Cancer. Diseases of the Colon & Rectum, 37, 272-277.
http://dx.doi.org/10.1007/BF02048166
[9] Ballesta, A.M., Molina, R., Filella, X., Jo, J. and Giménez, N. (1995) Carcinoembryonic Antigen in Staging and Follow-Up of Patients with Solid Tumors. Tumor Biology, 16, 32-41.
http://dx.doi.org/10.1159/000217926
[10] Woolfson, K. (1991) Tumor Markers in Cancer of the Colon and Rectum. Diseases of the Colon & Rectum, 34, 506-511. http://dx.doi.org/10.1007/BF02049939
[11] Fletcher, R.H. (1986) Carcinoembryonic Antigen. Annals of Internal Medicine, 104, 66-73.
http://dx.doi.org/10.7326/0003-4819-104-1-66
[12] Macdonald, J.S. (1999) Carcinoembryonic Antigen Screening: Pros and Cons. Seminars in Oncology, 26, 556-560.
[13] Iddings, D. and Bilchik, A. (2007) The Biologic Significance of Micrometastatic Disease and Sentinel Lymph Node Technology on Colorectal Cancer. Journal of Surgical Oncology, 96, 671-677.
http://dx.doi.org/10.1002/jso.20918
[14] Hyslop, T. and Waldman, S.A. (2013) Molecular Staging of Node Negative Patients with Colorectal Cancer. Journal of Cancer, 4, 193-199. http://dx.doi.org/10.7150/jca.5830
[15] Akiyoshi, T., Kobunai, T. and Watanabe, T. (2012) Recent Approaches to Identifying Biomarkers for High-Risk Stage II Colon Cancer. Surgery Today, 42, 1037-1045. http://dx.doi.org/10.1007/s00595-012-0324-4
[16] Ahmed, F.E. (2005) Molecular Markers That Predict Response to Colon Cancer Therapy. Expert Review of Molecular Diagnostics, 5, 353-375. http://dx.doi.org/10.1586/14737159.5.3.353
[17] Waldman, S.A., Hyslop, T., Schulz, S., Barkun, A., Nielsen, K., Haaf, J., et al. (2009) Association of GUCY2C Expression in Lymph Nodes with Time to Recurrence and Disease-Free Survival in pN0 Colorectal Cancer. JAMA, 301, 745-752. http://dx.doi.org/10.1001/jama.2009.141
[18] Mejia, A., Schulz, S., Hyslop, T., Weinberg, D.S. and Waldman, S.A. (2012) Molecular Staging Individualizing Cancer Management. Journal of Surgical Oncology, 105, 468-474.
http://dx.doi.org/10.1002/jso.21858
[19] Yarom, N. and Jonker, D.J. (2011) The Role of the Epidermal Growth Factor Receptor in the Mechanism and Treatment of Colorectal Cancer. Discovery Medicine, 11, 95-105.
[20] Vincenzi, B., Santini, D., Rabitti, C., Coppola, R., Beomonte Zobel, B., Trodella, L. and Tonini, G. (2006) Cetuximab and Irinotecan as Third-Line Therapy in Advanced Colorectal Cancer Patients: A Single Centre Phase II Trial. British Journal of Cancer, 94, 792-797.
http://dx.doi.org/10.1038/sj.bjc.6603018
[21] Spano, J.P., Lagorce, C., Atlan, D., Milano, G., Domont, J., Benamouzig, R., et al. (2005) Impact of EGFR Expression on Colorectal Cancer Patient Prognosis and Survival. Annals of Oncology, 16, 102-108.
http://dx.doi.org/10.1093/annonc/mdi006
[22] Scartozzi, M., Bearzi, I., Berardi, R., Mandolesi, A., Fabris, G. and Cascinu, S. (2004) Epidermal Growth Factor Receptor (EGFR) Status in Primary Colorectal Tumors Does Not Correlate with EGFR Expression in Related Metastatic Sites: Implications for Treatment with EGFR-Targeted Monoclonal Antibodies. Journal of Clinical Oncology, 22, 4772-4778. http://dx.doi.org/10.1200/JCO.2004.00.117
[23] McKay, J.A., Murray, L.J., Curran, S., Ross, V.G., Clark, C., Murray, G.I., Cassidy, J. and McLeod, H.L. (2002) Evaluation of the Epidermal Growth Factor Receptor (EGFR) in Colorectal Tumours and Lymph Node Metastases. European Journal of Cancer, 38, 2258-2264.
http://dx.doi.org/10.1016/S0959-8049(02)00234-4
[24] Porebska, I., Harlozińska, A. and Bojarowski, T. (2000) Expression of the Tyrosine Kinase Activity Growth Factor Receptors (EGFR, ERB B2, ERB B3) in Colorectal Adenocarcinomas and Adenomas. Tumor Biology, 21, 105-115. http://dx.doi.org/10.1159/000030116
[25] Cunningham, D., Humblet, Y., Siena, S., Khayat, D., Bleiberg, H., Santoro, A., et al. (2004) Cetuximab Monotherapy and Cetuximab Plus Irinotecan in Irinotecan-Refractory Metastatic Colorectal Cancer. New England Journal of Medicine, 351, 337-345. http://dx.doi.org/10.1056/NEJMoa033025
[26] Yan, L. and Beckman, R.A. (2005) Pharmacogenetics and Pharmacogenomics in Oncology Therapeutic Antibody Development. BioTechniques, 39, S565-S568. http://dx.doi.org/10.2144/000112043
[27] Saltz, L.B., Meropol, N.J., Loehrer Sr., P.J., Needle, M.N., Kopit, J. and Mayer, R.J. (2004) Phase II Trial of Cetuximab in Patients with Refractory Colorectal Cancer that Expresses the Epidermal Growth Factor Receptor. Journal of Clinical Oncology, 22, 1201-1208.
http://dx.doi.org/10.1200/JCO.2004.10.182
[28] Siddiqui, A.D. and Piperdi, B. (2010) KRAS Mutation in Colon Cancer: A Marker of Resistance to EGFR-I Therapy. Annals of Surgical Oncology, 17, 1168-1176. http://dx.doi.org/10.1245/s10434-009-0811-z
[29] Wu, C.C., Hsu, C.W., Chen, C.D., Yu, C.J., Chang, K.P., Tai, D.I., et al. (2010) Candidate Serological Biomarkers for Cancer Identified from the Secretomes of 23 Cancer Cell Lines and the Human Protein Atlas. Molecular & Cellular Proteomics, 9, 1100-1117. http://dx.doi.org/10.1074/mcp.M900398-MCP200
[30] Xue, H., Lu, B., Zhang, J., Wu, M.L., Huang, Q., Wu, Q., et al. (2010) Identification of Serum Biomarkers for Colorectal Cancer Metastasis Using a Differential Secretome Approach. Journal of Proteome Research, 9, 545-555. http://dx.doi.org/10.1021/pr9008817
[31] Jimenez, C.R., Knol, J.C., Meijer, G.A. and Fijneman, R.J. (2010) Proteomics of Colorectal Cancer: Overview of Discovery Studies and Identification of Commonly Identified Cancer-Associated Proteins and Candidate CRC Serum Markers. Journal of Proteomics, 73, 1873-1895.
http://dx.doi.org/10.1016/j.jprot.2010.06.004
[32] Fong, D., Moser, P., Krammel, C., Gostner, J.M., Margreiter, R., Mitterer, M., Gastl, G. and Spizzo, G. (2008) High Expression of TROP2 Correlates with Poor Prognosis in Pancreatic Cancer. British Journal of Cancer, 99, 1290-1295. http://dx.doi.org/10.1038/sj.bjc.6604677
[33] Fang, Y.J., Wang, G.Q., Lu, Z.H., Zhang, L., Li, J.B., Wu, X.J., et al. (2012) Different Effects of ERβ and TROP2 Expression in Chinese Patients with Early-Stage Colon Cancer. Tumor Biology, 33, 2227-2235. http://dx.doi.org/10.1007/s13277-012-0484-2
[34] Cubas, R., Zhang, S., Li, M., Chen, C.Y. and Yao, Q.Z. (2011) Chimeric Trop2 Virus-Like Particles: A Potential Immunotherapeutic Approach against Pancreatic Cancer. Journal of Immunotherapy, 34, 251-263. http://dx.doi.org/10.1097/CJI.0b013e318209ee72
[35] Bignotti, E., Todeschini, P., Calza, S., Falchetti, M., Ravanini, M., Tassi, R.A., et al. (2010) Trop-2 Overexpression as an Independent Marker for Poor Overall Survival in Ovarian Carcinoma Patients. European Journal of Cancer, 46, 944-953. http://dx.doi.org/10.1016/j.ejca.2009.12.019
[36] Thompson, S.J., Schatteman, G.C., Gown, A.M. and Bothwell, M. (1989) A Monoclonal Antibody against Nerve Growth Factor Receptor. Immunohistochemical Analysis of Normal and Neoplastic Human Tissue. American Journal of Clinical Pathology, 92, 415-423.
[37] Baker, D.L., Molenaar, W.M., Trojanowski, J.Q., Evans, A.E., Ross, A.H., Rorke, L.B., Packer, R.J., Lee, V.M.Y. and Pleasure, D. (1991) Nerve Growth Factor Receptor Expression in Peripheral and Central Neuroectodermal Tumors, Other Pediatric Brain Tumors, and during Development of the Adrenal Gland. American Journal of Pathology, 139, 115-122.
[38] Balik, V., Mirossay, P., Bohus, P., Sulla, I., Mirossay, L. and Sarissky, M. (2009) Flow Cytometry Analysis of Neural Differentiation Markers Expression in Human Glioblastomas May Predict Their Response to Chemotherapy. Cellular and Molecular Neurobiology, 29, 845-858.
http://dx.doi.org/10.1007/s10571-009-9366-6
[39] Pleasure, S.J., Reddy, U.R., Venkatakrishnan, G., Roy, A.K., Chen, J., Ross, A.H., Trojanowski, J.Q., Pleasure, D.E. and Lee, V.M. (1990) Introduction of Nerve Growth Factor (NGF) Receptors into a Medulloblastoma Cell Line Results in Expression of High- and Low-Affinity NGF Receptors but Not NGF-Mediated Differentiation. Proceedings of the National Academy of Sciences of the United States of America, 87, 8496-8500. http://dx.doi.org/10.1073/pnas.87.21.8496
[40] Maecker, H.T., Todd, S.C. and Levy, S. (1997) The Tetraspanin Superfamily: Molecular Facilitators. FASEB Journal, 11, 428-442.
[41] Hemler, M.E. (2005) Tetraspanin Functions and Associated Microdomains. Nature Reviews Molecular Cell Biology, 6, 801-811. http://dx.doi.org/10.1038/nrm1736
[42] Mita, A.C., Mita, M.M., Nawrocki, S.T. and Giles, F.J. (2008) Survivin: Key Regulator of Mitosis and Apoptosis and Novel Target for Cancer Therapeutics. Clinical Cancer Research, 14, 5000-5005.
http://dx.doi.org/10.1158/1078-0432.CCR-08-0746
[43] Pathi, S., Jutooru, I., Chadalapaka, G., Nair, V., Lee, S.O. and Safe, S. (2012) Aspirin Inhibits Colon Cancer Cell and Tumor Growth and Downregulates Specificity Protein (Sp) Transcription Factors. PLoS ONE, 7, e48208. http://dx.doi.org/10.1371/journal.pone.0048208             eww141014lx
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