Abstract
The cumulative lifetime risk for the development of colorectal cancer in the general population is 6 %. In many cases, early detection by fecal occult blood test is limited regarding sensitivity. Therefore, there is an urgent need for improved diagnostic tests in colorectal cancer. The recent development of high-throughput molecular analytic techniques should allow the rapid evaluation of new diagnostic markers. However, researchers are faced with an overwhelming number of potential markers form numerous colorectal cancer protein expression profiling studies. To address the challenge, we have carried out a comprehensive systematic review of colorectal cancer biomarkers from 13 published studies that compared the protein expression profiles of colorectal cancer and normal tissues. A protein ranking system that considers the number of comparisons in agreement, total sample sizes, average fold-change and direction of differential expression was devised. We observed that some proteins were consistently reported by multiple studies as differentially expressed with a statistically significant frequency (P < 0.05) in cancer versus normal tissues comparison. Our systematic review method identified proteins that were consistently reported as differentially expressed. A review of the top four candidates revealed proteins described previously as having diagnostic value as well as novel candidate biomarkers. These candidates should help to develop a panel of biomarkers with sufficient sensitivity and specificity for the diagnosis of colorectal cancer in a clinical setting.
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Weitz J, Koch M, Debus J, Hohler T, Galle PR, Buchler MW (2005) Colorectal cancer. Lancet 365:153–165
Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ (2005) Cancer statistics, 2005. CA Cancer J Clin 55:10–30
Woolf SH (2000) The best screening test for colorectal cancer—a personal choice. N Engl J Med 343:1641–1643
Walsh JM, Terdiman JP (2003) Colorectal cancer screening: scientific review. JAMA 289:1288–1296
Conrotto P, Roesli C, Rybak J, Kischel P, Waltregny D, Neri D, Castronovo V (2008) Identification of new accessible tumor antigens in human colon cancer by ex vivo protein biotinylation and comparative mass spectrometry analysis. Int J Cancer 123:2856–2864
Roblick UJ, Hirschberg D, Habermann JK, Palmberg C, Becker S, Kruger S, Gustafsson M, Bruch HP, Franzen B, Ried T, Bergmann T, Auer G et al (2004) Sequential proteome alterations during genesis and progression of colon cancer. Cell Mol Life Sci 61:1246–1255
Xing X, Lai M, Gartner W, Xu E, Huang Q, Li H, Chen G (2006) Identification of differentially expressed proteins in colorectal cancer by proteomics: down-regulation of secretagogin. Proteomics 6:2916–2923
Ma YL, Peng JY, Zhang P, Huang L, Liu WJ, Shen TY, Chen HQ, Zhou YK, Zhang M, Chu ZX, Qin HL (2009) Heterogeneous nuclear ribonucleoprotein A1 is identified as a potential biomarker for colorectal cancer based on differential proteomics technology. J Proteome Res 8:4525–4535
Kim H, Kang HJ, You KT, Kim SH, Lee KY, Kim TI, Kim C, Song SY, Kim HJ, Lee C (2006) Suppression of human selenium-binding protein 1 is a late event in colorectal carcinogenesis and is associated with poor survival. Proteomics 6:3466–3476
Alfonso P, Nunez A, Madoz-Gurpide J, Lombardia L, Sanchez L, Casal JI (2005) Proteomic expression analysis of colorectal cancer by two-dimensional differential gel electrophoresis. Proteomics 5:2602–2611
Polley AC, Mulholland F, Pin C, Williams EA, Bradburn DM, Mills SJ, Mathers JC, Johnson IT (2006) Proteomic analysis reveals field-wide changes in protein expression in the morphologically normal mucosa of patients with colorectal neoplasia. Cancer Res 66:6553–6562
Bi X, Lin Q, Foo TW, Joshi S, You T, Shen HM, Ong CN, Cheah PY, Eu KW, Hew CL (2006) Proteomic analysis of colorectal cancer reveals alterations in metabolic pathways: mechanism of tumorigenesis. Mol Cell Proteomics 5:1119–1130
Mazzanti R, Solazzo M, Fantappie O, Elfering S, Pantaleo P, Bechi P, Cianchi F, Ettl A, Giulivi C (2006) Differential expression proteomics of human colon cancer. Am J Physiol Gastrointest Liver Physiol 290:G1329–G1338
Tomonaga T, Matsushita K, Yamaguchi S, Oh-Ishi M, Kodera Y, Maeda T, Shimada H, Ochiai T, Nomura F (2004) Identification of altered protein expression and post-translational modifications in primary colorectal cancer by using agarose two-dimensional gel electrophoresis. Clin Cancer Res 10:2007–2014
Nibbe RK, Markowitz S, Myeroff L, Ewing R, Chance MR (2009) Discovery and scoring of protein interaction subnetworks discriminative of late stage human colon cancer. Mol Cell Proteomics 8:827–845
Friedman DB, Hill S, Keller JW, Merchant NB, Levy SE, Coffey RJ, Caprioli RM (2004) Proteome analysis of human colon cancer by two-dimensional difference gel electrophoresis and mass spectrometry. Proteomics 4:793–811
Celis JE, Gromov P (2003) Proteomics in translational cancer research: toward an integrated approach. Cancer Cell 3:9–15
Alessandro R, Belluco C, Kohn EC (2005) Proteomic approaches in colon cancer: promising tools for new cancer markers and drug target discovery. Clin Colorectal Cancer 4:396–402
Nedelkov D, Kiernan UA, Niederkofler EE, Tubbs KA, Nelson RW (2006) Population proteomics: the concept, attributes, and potential for cancer biomarker research. Mol Cell Proteomics 5:1811–1818
Tyers M, Mann M (2003) From genomics to proteomics. Nature 422:193–197
Phizicky E, Bastiaens PI, Zhu H, Snyder M, Fields S (2003) Protein analysis on a proteomic scale. Nature 422:208–215
Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey A, Chinnaiyan AM (2004) Large-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progression. Proc Natl Acad Sci USA 101:9309–9314
Cahan P, Ahmad AM, Burke H, Fu S, Lai Y, Florea L, Dharker N, Kobrinski T, Kale P, McCaffrey TA (2005) List of lists-annotated (LOLA): a database for annotation and comparison of published microarray gene lists. Gene 360:78–82
Shih W, Chetty R, Tsao MS (2005) Expression profiling by microarrays in colorectal cancer (review). Oncol Rep 13:517–524
Griffith OL, Melck A, Jones SJ, Wiseman SM (2006) Meta-analysis and meta-review of thyroid cancer gene expression profiling studies identifies important diagnostic biomarkers. J Clin Oncol 24:5043–5051
Chan SK, Griffith OL, Tai IT, Jones SJ (2008) Meta-analysis of colorectal cancer gene expression profiling studies identifies consistently reported candidate biomarkers. Cancer Epidemiol Biomarkers Prev 17:543–552
Sun W, Xing B, Sun Y, Du X, Lu M, Hao C, Lu Z, Mi W, Wu S, Wei H, Gao X, Zhu Y et al (2007) Proteome analysis of hepatocellular carcinoma by two-dimensional difference gel electrophoresis: novel protein markers in hepatocellular carcinoma tissues. Mol Cell Proteomics 6:1798–1808
Li Z, Zhao X, Bai S, Wang Z, Chen L, Wei Y, Huang C (2008) Proteomics identification of cyclophilin A as a potential prognostic factor and therapeutic target in endometrial carcinoma. Mol Cell Proteomics 7:1810–1823
Ma Y, Peng J, Liu W, Zhang P, Huang L, Gao B, Shen T, Zhou Y, Chen H, Chu Z, Zhang M, Qin H (2009) Proteomics identification of desmin as a potential oncofetal diagnostic and prognostic biomarker in colorectal cancer. Mol Cell Proteomics 8:1878–1890
Ma Y, Peng J, Huang L, Liu W, Zhang P, Qin H (2009) Searching for serum tumor markers for colorectal cancer using a 2-D DIGE approach. Electrophoresis 30:2591–2599
Huang HL, Stasyk T, Morandell S, Dieplinger H, Falkensammer G, Griesmacher A, Mogg M, Schreiber M, Feuerstein I, Huck CW, Stecher G, Bonn GK et al (2006) Biomarker discovery in breast cancer serum using 2-D differential gel electrophoresis/MALDI-TOF/TOF and data validation by routine clinical assays. Electrophoresis 27:1641–1650
Hartl FU, Hlodan R, Langer T (1994) Molecular chaperones in protein folding: the art of avoiding sticky situations. Trends Biochem Sci 19:20–25
Mosser DD, Morimoto RI (2004) Molecular chaperones and the stress of oncogenesis. Oncogene 23:2907–2918
Cappello F, Bellafiore M, Palma A, David S, Marciano V, Bartolotta T, Sciume C, Modica G, Farina F, Zummo G, Bucchieri F (2003) 60KDa chaperonin (HSP60) is over-expressed during colorectal carcinogenesis. Eur J Histochem 47:105–110
Cappello F, David S, Rappa F, Bucchieri F, Marasa L, Bartolotta TE, Farina F, Zummo G (2005) The expression of HSP60 and HSP10 in large bowel carcinomas with lymph node metastase. BMC Cancer 5:139
Lombardi D, Lacombe ML, Paggi MG (2000) nm23: unraveling its biological function in cell differentiation. J Cell Physiol 182:144–149
Fan Z, Beresford PJ, Oh DY, Zhang D, Lieberman J (2003) Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor. Cell 112:659–672
Aryee DN, Simonitsch I, Mosberger I, Kos K, Mann G, Schlogl E, Potschger U, Gadner H, Radaszkiewicz T, Kovar H (1996) Variability of nm23-H1/NDPK-A expression in human lymphomas and its relation to tumour aggressiveness. Br J Cancer 74:1693–1698
Niitsu N, Okamoto M, Honma Y, Nakamine H, Tamaru JI, Nakamura S, Yoshino T, Higashihara M, Hirano M, Okabe-Kado J (2003) Serum levels of the nm23-H1 protein and their clinical implication in extranodal NK/T-cell lymphoma. Leukemia 17:987–990
Lindmark G (1996) NM-23 H1 immunohistochemistry is not useful as predictor of metastatic potential of colorectal cancer. Br J Cancer 74:1413–1418
Heys SD, Langlois N, Smith IC, Walker LG, Eremin O (1998) NM23 gene product expression does not predict lymph node metastases or survival in young patients with colorectal cancer. Oncol Rep 5:735–739
Dursun A, Akyurek N, Gunel N, Yamac D (2002) Prognostic implication of nm23-H1 expression in colorectal carcinomas. Pathology 34:427–432
Forte A, D’Urso A, Gallinaro LS, Lo Storto G, Soda G, Bosco D, Bezzi M, Vietri F, Beltrami V (2002) NM23 expression as prognostic factor in colorectal carcinoma. G Chir 23:61–63
Brenner AS, Thebo JS, Senagore AJ, Duepree HJ, Gramlich T, Ormsby A, Lavery IC, Fazio VW (2003) Analysis of both NM23-h1 and NM23-H2 expression identifies “at-risk” patients with colorectal cancer. Am Surg 69:203–208; discussion 8
Yamaguchi A, Urano T, Fushida S, Furukawa K, Nishimura G, Yonemura Y, Miyazaki I, Nakagawara G, Shiku H (1993) Inverse association of nm23-H1 expression by colorectal cancer with liver metastasis. Br J Cancer 68:1020–1024
Martinez JA, Prevot S, Nordlinger B, Nguyen TM, Lacarriere Y, Munier A, Lascu I, Vaillant JC, Capeau J, Lacombe ML (1995) Overexpression of nm23-H1 and nm23-H2 genes in colorectal carcinomas and loss of nm23-H1 expression in advanced tumour stages. Gut 37:712–720
Tannapfel A, Kockerling F, Katalinic A, Wittekind C (1995) Expression of nm23-H1 predicts lymph node involvement in colorectal carcinoma. Dis Colon Rectum 38:651–654
Kapitanovic S, Cacev T, Berkovic M, Popovic-Hadzija M, Radosevic S, Seiwerth S, Spaventi S, Pavelic K, Spaventi R (2004) nm23-H1 expression and loss of heterozygosity in colon adenocarcinoma. J Clin Pathol 57:1312–1318
Royds JA, Cross SS, Silcocks PB, Scholefield JH, Rees RC, Stephenson TJ (1994) Nm23 ‘anti-metastatic’ gene product expression in colorectal carcinoma. J Pathol 172:261–266
Indinnimeo M, Cicchini C, Stazi A, Giarnieri E, Limiti MR, Ghini C, Vecchione A (1999) Correlation between nm23-H1 overexpression and clinicopathological variables in human anal canal carcinoma. Oncol Rep 6:1353–1356
Cohn KH, Wang FS, Desoto-LaPaix F, Solomon WB, Patterson LG, Arnold MR, Weimar J, Feldman JG, Levy AT, Leone A et al (1991) Association of nm23-H1 allelic deletions with distant metastases in colorectal carcinoma. Lancet 338:722–724
Leone A, McBride OW, Weston A, Wang MG, Anglard P, Cropp CS, Goepel JR, Lidereau R, Callahan R, Linehan WM et al (1991) Somatic allelic deletion of nm23 in human cancer. Cancer Res 51:2490–2493
Cohn KH, Ornstein DL, Wang F, LaPaix FD, Phipps K, Edelsberg C, Zuna R, Mott LA, Dunn JL (1997) The significance of allelic deletions and aneuploidy in colorectal carcinoma. Results of a 5-year follow-up study. Cancer 79:233–244
Myeroff LL, Markowitz SD (1993) Increased nm23-H1 and nm23-H2 messenger RNA expression and absence of mutations in colon carcinomas of low and high metastatic potential. J Natl Cancer Inst 85:147–152
Cawkwell L, Lewis FA, Quirke P (1994) Frequency of allele loss of DCC, p53, RBI, WT1, NF1, NM23 and APC/MCC in colorectal cancer assayed by fluorescent multiplex polymerase chain reaction. Br J Cancer 70:813–818
Clark LC, Combs GF Jr, Turnbull BW, Slate EH, Chalker DK, Chow J, Davis LS, Glover RA, Graham GF, Gross EG, Krongrad A, Lesher JL Jr et al (1996) Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA 276:1957–1963
Fleming J, Ghose A, Harrison PR (2001) Molecular mechanisms of cancer prevention by selenium compounds. Nutr Cancer 40:42–49
Rayman MP (2000) The importance of selenium to human health. Lancet 356:233–241
Reid ME, Duffield-Lillico AJ, Garland L, Turnbull BW, Clark LC, Marshall JR (2002) Selenium supplementation and lung cancer incidence: an update of the nutritional prevention of cancer trial. Cancer Epidemiol Biomarkers Prev 11:1285–1291
Zhuo H, Smith AH, Steinmaus C (2004) Selenium and lung cancer: a quantitative analysis of heterogeneity in the current epidemiological literature. Cancer Epidemiol Biomarkers Prev 13:771–778
Bekku S, Mochizuki H, Yamamoto T, Ueno H, Takayama E, Tadakuma T (2000) Expression of carbonic anhydrase I or II and correlation to clinical aspects of colorectal cancer. Hepatogastroenterology 47:998–1001
Kivela AJ, Saarnio J, Karttunen TJ, Kivela J, Parkkila AK, Pastorekova S, Pastorek J, Waheed A, Sly WS, Parkkila TS, Rajaniemi H (2001) Differential expression of cytoplasmic carbonic anhydrases, CA I and II, and membrane-associated isozymes, CA IX and XII, in normal mucosa of large intestine and in colorectal tumors. Dig Dis Sci 46:2179–2186
Mori M, Staniunas RJ, Barnard GF, Jessup JM, Steele GD Jr, Chen LB (1993) The significance of carbonic anhydrase expression in human colorectal cancer. Gastroenterology 105:820–826
Acknowledgments
The authors thank Professor Simon Chan (Canada’s Michael Smith Genome Sciences Centre, British Columbia Cancer Research Centre) for some technic directions on this study. This work was financially sponsored by Shanghai Rising-Star Program (No. 11QA1404800), the Grants from the National Natural Science Foundation of China (No. 81001069), and the National 863 High Technology Foundation (No. 2009AA02Z118).
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The authors declare that no competing interests exist.
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Yanlei Ma and Huanlong Qin contributed equally to this work.
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Ma, Y., Zhang, P., Wang, F. et al. Searching for consistently reported up- and down-regulated biomarkers in colorectal cancer: a systematic review of proteomic studies. Mol Biol Rep 39, 8483–8490 (2012). https://doi.org/10.1007/s11033-012-1702-0
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DOI: https://doi.org/10.1007/s11033-012-1702-0