Generic placeholder image

Current Proteomics

Editor-in-Chief

ISSN (Print): 1570-1646
ISSN (Online): 1875-6247

Research Article

Identification of the Altered Proteins Related to Colon Carcinogenesis by iTRAQ-based Quantitative Proteomic Analysis

Author(s): Chunhua Luo, Defu Yao, Teck Kwang Lim, Qingsong Lin and Yingfu Liu*

Volume 16, Issue 4, 2019

Page: [297 - 306] Pages: 10

DOI: 10.2174/1570164616666181129111542

Price: $65

Abstract

Background: The molecular mechanisms or valuable biomarkers for early diagnosis of colorectal cancer (CRC) are not fully elucidated yet.

Objective: To understand the proteomic changes at the global level in the carcinogenesis of CRC, differentially expressed proteins between normal intestinal epithelial cells CCD841 and colorectal cancer cells HCT116 were identified.

Method: The isobaric tags for relative and absolute quantitation (iTRAQ) coupled with 2D LC-MS/MS proteomic approach were performed for screening the altered proteins between cells CCD841 and HCT116.

Results: A total of 1947 proteins were identified after filtering and using a 1% false discovery rate. Based on a final cutoff (> 3.16 and < 0.32), 229 proteins were found to be significantly altered, among which 95 (41%) were up-regulated while 134 (59%) were down-regulated. Gene Ontology analysis revealed that the differentially expressed proteins were mainly cell part proteins involved in cellular process and binding in terms of subcellular distribution, biological process, and molecular function. KEGG analysis indicated that the differentially expressed proteins were significantly involved in the process of focal adhesion, pathogenic Escherichia coli infection, leukocyte transendothelial migration, bacterial invasion of epithelial cells, regulation of actin cytoskeleton, DNA replication and so on.

Conclusion: Collectively, our data identified differentially expressed proteins in colon cancer carcinogenesis, which could provide the clues on unraveling the molecular mechanism of CRC.

Keywords: Quantitative proteomics, colon cancer, carcinogenesis, iTRAQ, gene, heredity.

Graphical Abstract

[1]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2018. CA Cancer J. Clin., 2018, 68(1), 7-30.
[2]
Chen, W.; Zheng, R.; Zhang, S.; Zhao, P.; Zeng, H.; Zou, X. Report of cancer incidence and mortality in China, 2010. Ann. Transl. Med., 2014, 2(7), 61-67.
[3]
Qin, Q.; Yang, L.; Sun, Y.K.; Ying, J.M.; Song, Y.; Zhang, W.; Wang, J.W.; Zhou, A.P. Comparison of 627 patients with right- and left-sided colon cancer in China: differences in clinicopathology, recurrence, and survival. Chronic Dis. Transl. Med., 2017, 3(1), 51-59.
[4]
Isella, C.; Terrasi, A.; Bellomo, S.E.; Petti, C.; Galatola, G.; Muratore, A.; Mellano, A.; Senetta, R.; Cassenti, A.; Sonetto, C.; Inghirami, G.; Trusolino, L.; Fekete, Z.; De Ridder, M.; Cassoni, P.; Storme, G.; Bertotti, A.; Medico, E. Stromal contribution to the colorectal cancer transcriptome. Nat. Genet., 2015, 47(4), 312-319.
[5]
Guinney, J.; Dienstmann, R.; Wang, X.; de Reynies, A.; Schlicker, A.; Soneson, C.; Marisa, L.; Roepman, P.; Nyamundanda, G.; Angelino, P.; Bot, B.M.; Morris, J.S.; Simon, I.M.; Gerster, S.; Fessler, E.; De Sousa, E.M.F.; Missiaglia, E.; Ramay, H.; Barras, D.; Homicsko, K.; Maru, D.; Manyam, G.C.; Broom, B.; Boige, V.; Perez-Villamil, B.; Laderas, T.; Salazar, R.; Gray, J.W.; Hanahan, D.; Tabernero, J.; Bernards, R.; Friend, S.H.; Laurent-Puig, P.; Medema, J.P.; Sadanandam, A.; Wessels, L.; Delorenzi, M.; Kopetz, S.; Vermeulen, L.; Tejpar, S. The consensus molecular subtypes of colorectal cancer. Nat. Med., 2015, 21(11), 1350-1356.
[6]
Dienstmann, R.; Vermeulen, L.; Guinney, J.; Kopetz, S.; Tejpar, S.; Tabernero, J. Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer. Nat. Rev. Cancer, 2017, 17(2), 79-92.
[7]
Suehiro, Y.; Wong, C.W.; Chirieac, L.R.; Kondo, Y.; Shen, L.; Webb, C.R.; Chan, Y.W.; Chan, A.S.; Chan, T.L.; Wu, T.T.; Rashid, A.; Hamanaka, Y.; Hinoda, Y.; Shannon, R.L.; Wang, X.; Morris, J.; Issa, J.P.; Yuen, S.T.; Leung, S.Y.; Hamilton, S.R. Epigenetic-genetic interactions in the APC/WNT, RAS/RAF, and P53 pathways in colorectal carcinoma. Clin. Cancer Res., 2008, 14(9), 2560-2569.
[8]
Chan, C.C.; Fan, C.W.; Kuo, Y.B.; Chen, Y.H.; Chang, P.Y.; Chen, K.T.; Hung, R.P.; Chan, E.C. Multiple serological biomarkers for colorectal cancer detection. Int. J. Cancer, 2010, 126(7), 1683-1690.
[9]
Mori, K.; Toiyama, Y.; Otake, K.; Ide, S.; Imaoka, H.; Okigami, M.; Okugawa, Y.; Fujikawa, H.; Saigusa, S.; Hiro, J.; Kobayashi, M.; Ohi, M.; Tanaka, K.; Inoue, Y.; Kobayashi, Y.; Mohri, Y.; Kobayashi, I.; Goel, A.; Kusunoki, M. Successful identification of a predictive biomarker for lymph node metastasis in colorectal cancer using a proteomic approach. Oncotarget, 2017, 8(63), 106935-106947.
[10]
Tu, C.; Mojica, W.; Straubinger, R.M.; Li, J.; Shen, S.; Qu, M.; Nie, L.; Roberts, R.; An, B.; Qu, J. Quantitative proteomic profiling of paired cancerous and normal colon epithelial cells isolated freshly from colorectal cancer patients. Proteomics Clin. Appl., 2017, 11(5-6)
[http://dx.doi.org/10.1002/prca.20160015]
[11]
Saponaro, C.; Sergio, S.; Coluccia, A.; De Luca, M.; La Regina, G.; Mologni, L.; Famiglini, V.; Naccarato, V.; Bonetti, D.; Gautier, C.; Gianni, S.; Vergara, D.; Salzet, M.; Fournier, I.; Bucci, C.; Silvestri, R.; Passerini, C.G.; Maffia, M.; Coluccia, A.M.L. β-catenin knockdown promotes NHERF1-mediated survival of colorectal cancer cells: Implications for a double-targeted therapy. Oncogene, 2018, 37(24), 3301-3316.
[12]
Torres, S.; Garcia-Palmero, I.; Marin-Vicente, C.; Bartolome, R.A.; Calvino, E.; Fernandez-Acenero, M.J.; Casal, J.I. Proteomic characterization of transcription and splicing factors associated with a metastatic phenotype in colorectal cancer. J. Proteome Res., 2018, 17(1), 252-264.
[13]
Shruthi, B.S.; Vinodhkumar, P. Selvamani. Proteomics: A new perspective for cancer. Adv. Biomed. Res., 2016, 5, 67.
[14]
Naxerova, K.; Reiter, J.G.; Brachtel, E.; Lennerz, J.K.; van de Wetering, M.; Rowan, A.; Cai, T.; Clevers, H.; Swanton, C.; Nowak, M.A.; Elledge, S.J.; Jain, R.K. Origins of lymphatic and distant metastases in human colorectal cancer. Science, 2017, 357(6346), 55-60.
[15]
Tyanova, S.; Cox, J. Perseus: A bioinformatics platform for integrative analysis of proteomics data in cancer research. Methods Mol. Biol., 2018, 1711, 133-148.
[16]
Li, L.; Yang, D.; Cui, D.; Li, Y.; Nie, Z.; Wang, J.; Liang, L. Quantitative proteomics analysis of the role of tetraspanin-8 in the drug resistance of gastric cancer. Int. J. Oncol., 2018, 52(2), 473-484.
[17]
Li, X.H.; Li, C.; Xiao, Z.Q. Proteomics for identifying mechanisms and biomarkers of drug resistance in cancer. J. Proteomics, 2011, 74(12), 2642-2649.
[18]
Peng, W.; Zhang, Y.; Zhu, R.; Mechref, Y. Comparative membrane proteomics analyses of breast cancer cell lines to understand the molecular mechanism of breast cancer brain metastasis. Electrophoresis, 2017, 38(17), 2124-2134.
[19]
Chen, C.; Zhang, L.G.; Liu, J.; Han, H.; Chen, N.; Yao, A.L.; Kang, S.S.; Gao, W.X.; Shen, H.; Zhang, L.J.; Li, Y.P.; Cao, F.H.; Li, Z.G. Bioinformatics analysis of differentially expressed proteins in prostate cancer based on proteomics data. OncoTargets Ther., 2016, 9, 1545-1557.
[20]
Jiang, Z.; Shen, H.; Tang, B.; Chen, H.; Yu, Q.; Ji, X.; Wang, L. Identification of diagnostic markers involved in the pathogenesis of gastric cancer through iTRAQ-based quantitative proteomics. Data Brief, 2017, 11, 122-126.
[21]
Wang, L.N.; Tong, S.W.; Hu, H.D.; Ye, F.; Li, S.L.; Ren, H.; Zhang, D.Z.; Xiang, R.; Yang, Y.X. Quantitative proteome analysis of ovarian cancer tissues using a iTRAQ approach. J. Cell. Biochem., 2012, 113(12), 3762-3772.
[22]
Zhang, Q.; Huang, S.; Luo, H.; Zhao, X.; Wu, G.; Wu, D. Eight-plex iTRAQ labeling and quantitative proteomic analysis for human bladder cancer. Am. J. Cancer Res., 2017, 7(4), 935-945.
[23]
Ghosh, D.; Yu, H.; Tan, X.F.; Lim, T.K.; Zubaidah, R.M.; Tan, H.T.; Chung, M.C.; Lin, Q. Identification of key players for colorectal cancer metastasis by iTRAQ quantitative proteomics profiling of isogenic SW480 and SW620 cell lines. J. Proteome Res., 2011, 10(10), 4373-4387.
[24]
Lu, X.; Zhu, H. Tube-gel digestion: A novel proteomic approach for high throughput analysis of membrane proteins. Mol. Cell. Proteomics, 2005, 4(12), 1948-1958.
[25]
Yu, H.; Wakim, B.; Li, M.; Halligan, B.; Tint, G.S.; Patel, S.B. Quantifying raft proteins in neonatal mouse brain by ‘tube-gel’ protein digestion label-free shotgun proteomics. Proteome Sci., 2007, 5, 17.
[26]
Gan, C.S.; Chong, P.K.; Pham, T.K.; Wright, P.C. Technical, experimental, and biological variations in isobaric tags for relative and absolute quantitation (iTRAQ). J. Proteome Res., 2007, 6(2), 821-827.
[27]
Fearon, E.R. Molecular genetics of colorectal cancer. Annu. Rev. Pathol., 2011, 6, 479-507.
[28]
Budinska, E.; Popovici, V.; Tejpar, S.; D’Ario, G.; Lapique, N.; Sikora, K.O.; Di Narzo, A.F.; Yan, P.; Hodgson, J.G.; Weinrich, S.; Bosman, F.; Roth, A.; Delorenzi, M. Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer. J. Pathol., 2013, 231(1), 63-76.
[29]
Vogelstein, B.; Papadopoulos, N.; Velculescu, V.E.; Zhou, S.; Diaz, L.A. Jr.; Kinzler, K.W. Cancer genome landscapes. Science, 2013, 339(6127), 1546-1558.
[30]
Li, T.; Guo, H.; Song, Y.; Zhao, X.; Shi, Y.; Lu, Y.; Hu, S.; Nie, Y.; Fan, D.; Wu, K. Loss of vinculin and membrane-bound beta-catenin promotes metastasis and predicts poor prognosis in colorectal cancer. Mol. Cancer, 2014, 13, 263.
[31]
Miyanaga, K.; Kato, Y.; Nakamura, T.; Matsumura, M.; Amaya, H.; Horiuchi, T.; Chiba, Y.; Tanaka, K. Expression and role of thrombospondin-1 in colorectal cancer. Anticancer Res., 2002, 22(6C), 3941-3948.
[32]
Lin, Q.; Lim, H.S.; Lin, H.L.; Tan, H.T.; Lim, T.K.; Cheong, W.K.; Cheah, P.Y.; Tang, C.L.; Chow, P.K.; Chung, M.C. Analysis of colorectal cancer glyco-secretome identifies laminin beta-1 (LAMB1) as a potential serological biomarker for colorectal cancer. Proteomics, 2015, 15(22), 3905-3920.
[33]
Craig, D.H.; Haimovich, B.; Basson, M.D. Alpha-actinin-1 phosphorylation modulates pressure-induced colon cancer cell adhesion through regulation of focal adhesion kinase-Src interaction. Am. J. Physiol. Cell Physiol., 2007, 293(6), C1862-C1874.
[34]
Choi, H.J.; Kim, J.; Do, K.H.; Park, S.H.; Moon, Y. Enteropathogenic Escherichia coli-induced macrophage inhibitory cytokine 1 mediates cancer cell survival: An in vitro implication of infection-linked tumor dissemination. Oncogene, 2013, 32(41), 4960-4969.
[35]
He, Z.Y.; Wen, H.; Shi, C.B.; Wang, J. Up-regulation of hnRNP A1, Ezrin, tubulin beta-2C and Annexin A1 in sentinel lymph nodes of colorectal cancer. World J. Gastroenterol., 2010, 16(37), 4670-4676.
[36]
Mariani, M.; Zannoni, G.F.; Sioletic, S.; Sieber, S.; Martino, C.; Martinelli, E.; Coco, C.; Scambia, G.; Shahabi, S.; Ferlini, C. Gender influences the class III and V beta-tubulin ability to predict poor outcome in colorectal cancer. Clin. Cancer Res., 2012, 18(10), 2964-2975.
[37]
Zhao, X.; Yue, C.; Chen, J.; Tian, C.; Yang, D.; Xing, L.; Liu, H.; Jin, Y. Class III β-tubulin in colorectal cancer: tissue distribution and clinical analysis of Chinese patients. Med. Sci. Monit., 2016, 22, 3915-3924.
[38]
Aggarwal, A.; Schulz, H.; Manhardt, T.; Bilban, M.; Thakker, R.V.; Kallay, E. Expression profiling of colorectal cancer cells reveals inhibition of DNA replication licensing by extracellular calcium. Biochim. Biophys. Acta, 2017, 1864(6), 987-996.
[39]
Pillaire, M.J.; Selves, J.; Gordien, K.; Gourraud, P.A.; Gentil, C.; Danjoux, M.; Do, C.; Negre, V.; Bieth, A.; Guimbaud, R.; Trouche, D.; Pasero, P.; Mechali, M.; Hoffmann, J.S.; Cazaux, C.A. ‘DNA replication’ signature of progression and negative outcome in colorectal cancer. Oncogene, 2010, 29(6), 876-887.
[40]
Sakuma, K.; Sasaki, E.; Kimura, K.; Komori, K.; Shimizu, Y.; Yatabe, Y.; Aoki, M. HNRNPLL stabilizes mRNA for DNA replication proteins and promotes cell cycle progression in colorectal cancer cells. Cancer Sci., 2018, 109(8), 2458-2468.
[41]
Kim, S.H.; Kim, S.C.; Ku, J.L. Metformin increases chemo-sensitivity via gene downregulation encoding DNA replication proteins in 5-Fu resistant colorectal cancer cells. Oncotarget, 2017, 8(34), 56546-56557.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy