Abstract
Colorectal cancer is an important public health concern leading to significant cancer associate mortality. A vast majority of colon cancer arises from polyp which later follows adenoma, adenocarcinoma, and carcinoma sequence. This whole process takes several years to complete and recent genomic and proteomic technologies are identifying several targets involved in each step of polyp to carcinoma transformation in a large number of studies. Current text presents interaction network of targets involved in polyp to carcinoma transformation. In addition, important targets involved in each step according to network biological parameters are also presented. The functional overrepresentation analysis of each step targets and common top biological processes and pathways involved in carcinoma indicate several insights about this whole mechanism. Interaction networks indicate TP53, AKT1, GAPDH, INS, EGFR, and ALB as the most important targets commonly involved in polyp to carcinoma sequence. Though several important pathways are known to be involved in CRC, the central common involvement of PI3K-AKT indicates its potential for devising CRC management strategies. The common and central targets and pathways involved in polyp to carcinoma progression can shed light on its mechanism and potential management strategies. The data-driven approach aims to add valuable inputs to the mechanism of the years-long polyp-carcinoma sequence.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aarons CB, Shanmugan S, Bleier JI (2014) Management of malignant colon polyps: current status and controversies. World J Gastroenterol 20(43):16178–16183. https://doi.org/10.3748/wjg.v20.i43.16178
Armaghany T, Wilson JD, Chu Q, Mills G (2012) Genetic alterations in colorectal cancer. Gastrointest Cancer Res GCR 5(1):19–27
Baandrup L, Thomsen LT, Olesen TB, Andersen KK, Norrild B, Kjaer SK (2014) The prevalence of human papillomavirus in colorectal adenomas and adenocarcinomas: a systematic review and meta-analysis. Eur J Cancer 50(8):1446–1461. https://doi.org/10.1016/j.ejca.2014.01.019
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. https://doi.org/10.3322/caac.21492
Bronner MP, Haggitt RC (1993) The polyp-cancer sequence: do all colorectal cancers arise from benign adenomas? Gastrointest Endosc Clin N Am 3(4):611–622. https://doi.org/10.1016/S1052-5157(18)30534-8
Bujanda L, Cosme A, Gil I, Arenas-Mirave JI (2010) Malignant colorectal polyps. World J Gastroenterol 16(25):3103–3111. https://doi.org/10.3748/wjg.v16.i25.3103
Busher JT (1990) Serum albumin and globulin. In: Walker HK, Hall WD, Hurst JW (eds) Clinical methods: the history, physical, and laboratory examinations
Butera G, Pacchiana R, Mullappilly N, Margiotta M, Bruno S, Conti P, Riganti C (2018) Mutant p53 prevents GAPDH nuclear translocation in pancreatic cancer cells favoring glycolysis and 2-deoxyglucose sensitivity. Biochim Biophys Acta 12:1914–1923. https://doi.org/10.1016/j.bbamcr.2018.10.005
Cancer Genome Atlas N (2012) Comprehensive molecular characterization of human colon and rectal cancer. Nature 487(7407):330–337. https://doi.org/10.1038/nature11252
Caraceni P, Tufoni M, Bonavita ME (2013) Clinical use of albumin. Blood Transf 11:18–25. https://doi.org/10.2450/2013.005s
Chavali LB, Hu K, Sheth A, Gao N, Xiong W, Zhang L (2020) Colorectal sessile serrated lesion with large size or synchronous neoplasm: a prospective study. Eur J Gastroenterol Hepatol 32(2):199–204. https://doi.org/10.1097/MEG.0000000000001642
Chen Z, Wang C, Dong H, Wang X, Gao F, Zhang S, Zhang X (2020) Aspirin has a better effect on PIK3CA mutant colorectal cancer cells by PI3K/Akt/Raptor pathway. Mol Med 26(1):14. https://doi.org/10.1186/s10020-020-0139-5
Cho Y-H, Ro EJ, Yoon J-S, Mizutani T, Kang D-W, Park J-C, Il Kim T, Clevers H, Choi K-Y (2020) 5-FU promotes stemness of colorectal cancer via p53-mediated WNT/β-catenin pathway activation. Nat Commun 11(1):5321. https://doi.org/10.1038/s41467-020-19173-2
Damin DC, Caetano MB, Rosito MA, Schwartsmann G, Damin AS, Frazzon AP, Ruppenthal RD, Alexandre CO (2007) Evidence for an association of human papillomavirus infection and colorectal cancer. Eur J Surg Oncol 33(5):569–574. https://doi.org/10.1016/j.ejso.2007.01.014
Damin DC, Ziegelmann PK, Damin AP (2013) Human papillomavirus infection and colorectal cancer risk: a meta-analysis. Colorec Dis 15(8):e420-428. https://doi.org/10.1111/codi.12257
De Rosa M, Rega D, Costabile V, Duraturo F, Niglio A, Izzo P, Pace U, Delrio P (2016) The biological complexity of colorectal cancer: insights into biomarkers for early detection and personalized care. Ther Adv Gastroenterol 9(6):861–886. https://doi.org/10.1177/1756283X16659790
Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61(5):759–767. https://doi.org/10.1016/0092-8674(90)90186-i
Fornito A, Zalesky A, Bullmore ET (2016) Chapter 4 - Node Degree and Strength. In: Fornito A, Zalesky A, Bullmore ET (eds) Fundamentals of Brain Network Analysis. Academic Press, San Diego. https://doi.org/10.1016/B978-0-12-407908-3.00004-2
Giovannucci E (1995) Insulin and colon cancer. Cancer Causes Control CCC 6(2):164–179. https://doi.org/10.1007/BF00052777
Giovannucci E (2001) Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J Nutr 131(11 Suppl):3109S-3120S. https://doi.org/10.1093/jn/131.11.3109S
Giovannucci E (2007) Metabolic syndrome, hyperinsulinemia, and colon cancer: a review. Am J Clin Nutr 86(3):s836-842. https://doi.org/10.1093/ajcn/86.3.836S
Gonzalez-Trejo S, Carrillo JF, Carmona-Herrera DD, Baz-Gutierrez P, Herrera-Goepfert R, Nunez G, Ochoa-Carrillo FJ, Gallardo-Rincon D, Aiello-Crocifoglio V, Onate-Ocana LF (2017) Baseline serum albumin and other common clinical markers are prognostic factors in colorectal carcinoma: a retrospective cohort study. Medicine 96(15):e6610. https://doi.org/10.1097/MD.0000000000006610
He X, Zhang J (2006) Why do hubs tend to be essential in protein networks? PLoS Genet 2(6):e88. https://doi.org/10.1371/journal.pgen.0020088
Hirata T, Nakamoto M, Nakamura M, Kinjo N, Hokama A, Kinjo F, Fujita J (2007) Low prevalence of human T cell lymphotropic virus type 1 infection in patients with gastric cancer. J Gastroenterol Hepatol 22(12):2238–2241. https://doi.org/10.1111/j.1440-1746.2006.04740.x
Iacopetta B (2003) TP53 mutation in colorectal cancer. Hum Mutat 21(3):271–276. https://doi.org/10.1002/humu.10175
Johnston L, Carey F (2020) Pathology of colorectal polyps and cancer. Surg Infect (larchmt) 38(1):12–17. https://doi.org/10.1016/j.mpsur.2019.10.012
Jung G, Hernandez-Illan E, Moreira L, Balaguer F, Goel A (2020) Epigenetics of colorectal cancer: biomarker and therapeutic potential. Nat Rev Gastroenterol Hepatol 17(2):111–130. https://doi.org/10.1038/s41575-019-0230-y
Kamarudin MNA, Sarker MMR, Zhou JR, Parhar I (2019) Metformin in colorectal cancer: molecular mechanism, preclinical and clinical aspects. J Exp Clin Cancer Res CR 38(1):491. https://doi.org/10.1186/s13046-019-1495-2
Khan AA, Khan Z, Malik A, Kalam MA, Cash P, Ashraf MT, Alshamsan A (2017) Colorectal cancer-inflammatory bowel disease nexus and felony of Escherichia coli. Life Sci 180:60–67. https://doi.org/10.1016/j.lfs.2017.05.016
Knekt P, Hakulinen T, Leino A, Heliovaara M, Reunanen A, Stevens R (2000) Serum albumin and colorectal cancer risk. Eur J Clin Nutr 54(6):460–462. https://doi.org/10.1038/sj.ejcn.1600997
Krasinskas AM (2011) EGFR signaling in colorectal carcinoma. Pathol Res Int 2011:932932. https://doi.org/10.4061/2011/932932
Kuipers EJ, Grady WM, Lieberman D, Seufferlein T, Sung JJ, Boelens PG, van de Velde CJH, Watanabe T (2015) Colorectal cancer. Nat Rev Dis Primers 1(1):15065. https://doi.org/10.1038/nrdp.2015.65
Leslie A, Carey FA, Pratt NR, Steele RJ (2002) The colorectal adenoma-carcinoma sequence. Br J Surg 89(7):845–860. https://doi.org/10.1046/j.1365-2168.2002.02120.x
Lieberman DA, Rex DK, Winawer SJ, Giardiello FM, Johnson DA, Levin TR (2012) Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 143(3):844–857. https://doi.org/10.1053/j.gastro.2012.06.001
Matsumoto S, Yamasaki K, Tsuji K, Shirahama S (2008) Human T lymphotropic virus type 1 infection and gastric cancer development in Japan. J Infect Dis 198(1):10–15. https://doi.org/10.1086/588733
Nazha B, Moussaly E, Zaarour M, Weerasinghe C, Azab B (2015) Hypoalbuminemia in colorectal cancer prognosis: nutritional marker or inflammatory surrogate? World J Gastrointest Surg 7(12):370–377. https://doi.org/10.4240/wjgs.v7.i12.370
Pan J, Cen L, Xu L, Miao M, Li Y, Yu C, Shen Z (2020) Prevalence and risk factors for colorectal polyps in a Chinese population: a retrospective study. Sci Rep 10(1):6974. https://doi.org/10.1038/s41598-020-63827-6
Pavlopoulou A, Spandidos DA, Michalopoulos I (2015) Human cancer databases (review). Oncol Rep 33(1):3–18. https://doi.org/10.3892/or.2014.3579
Pinero J, Ramirez-Anguita JM, Sauch-Pitarch J, Ronzano F, Centeno E, Sanz F, Furlong LI (2020) The DisGeNET knowledge platform for disease genomics: 2019 update. Nucleic Acids Res 48(D1):D845–D855. https://doi.org/10.1093/nar/gkz1021
Pino MS, Chung DC (2010) The chromosomal instability pathway in colon cancer. Gastroenterology 138(6):2059–2072. https://doi.org/10.1053/j.gastro.2009.12.065
Raudvere U, Kolberg L, Kuzmin I, Arak T, Adler P, Peterson H, Vilo J (2019) g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update). Nucleic Acids Res 47(W1):W191–W198. https://doi.org/10.1093/nar/gkz369
Rutter MD, East J, Rees CJ, Cripps N, Docherty J, Dolwani S, Kaye PV, Monahan KJ, Novelli MR, Plumb A, Saunders BP, Thomas-Gibson S, Tolan DJM, Whyte S, Bonnington S, Scope A, Wong R, Hibbert B, Marsh J, Moores B, Cross A, Sharp L (2020) British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/Public Health England post-polypectomy and post-colorectal cancer resection surveillance guidelines. Gut 69(2):201–223. https://doi.org/10.1136/gutjnl-2019-319858
Seo HA, Moeng S, Sim S, Kuh HJ, Choi SY, Park JK (2019) MicroRNA-based combinatorial cancer therapy: effects of microRNAs on the efficacy of anti-cancer therapies. Cells. https://doi.org/10.3390/cells9010029
Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504. https://doi.org/10.1101/gr.1239303
Siddiqui AA (2011) Metabolic syndrome and its association with colorectal cancer: a review. Am J Med Sci 341(3):227–231. https://doi.org/10.1097/MAJ.0b013e3181df9055
Spano JP, Lagorce C, Atlan D, Milano G, Domont J, Benamouzig R, Attar A, Benichou J, Martin A, Morere JF, Raphael M, Penault-Llorca F, Breau JL, Fagard R, Khayat D, Wind P (2005) Impact of EGFR expression on colorectal cancer patient prognosis and survival. Ann Oncol 16(1):102–108. https://doi.org/10.1093/annonc/mdi006
Stelzer G, Rosen N, Plaschkes I, Zimmerman S, Twik M, Fishilevich S, Stein TI, Nudel R, Lieder I, Mazor Y, Kaplan S, Dahary D, Warshawsky D, Guan-Golan Y, Kohn A, Rappaport N, Safran M, Lancet D (2016) The GeneCards suite: From gene data mining to disease genome sequence analyses. Curr Protoc Bioinform. https://doi.org/10.1002/cpbi.5
Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P, Jensen LJ, Mering CV (2019) STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 47(D1):D607–D613. https://doi.org/10.1093/nar/gky1131
Tang Z, Yuan S, Hu Y, Zhang H, Wu W, Zeng Z, Yang J, Yun J, Xu R, Huang P (2012) Over-expression of GAPDH in human colorectal carcinoma as a preferred target of 3-bromopyruvate propyl ester. J Bioenerg Biomembr 44(1):117–125. https://doi.org/10.1007/s10863-012-9420-9
Tarrado-Castellarnau M, Diaz-Moralli S, Polat IH, Sanz-Pamplona R, Alenda C, Moreno V, Castells A, Cascante M (2017) Glyceraldehyde-3-phosphate dehydrogenase is overexpressed in colorectal cancer onset. Transl Med Commun 2(1):6. https://doi.org/10.1186/s41231-017-0015-7
Vivanco I, Sawyers CL (2002) The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2(7):489–501. https://doi.org/10.1038/nrc839
Weng M-l, Chen W-k, Chen X-y, Lu H, Sun Z-r, Yu Q, Sun P-f, Xu Y-j, Zhu M-m, Jiang N, Zhang J, Zhang J-p, Song Y-l, Ma D, Zhang X-p, Miao C-h (2020) Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression. Nat Commun 11(1):1869. https://doi.org/10.1038/s41467-020-15795-8
Zauber AG, Winawer SJ, O’Brien MJ, Lansdorp-Vogelaar I, van Ballegooijen M, Hankey BF, Shi W, Bond JH, Schapiro M, Panish JF, Stewart ET, Waye JD (2012) Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N Engl J Med 366(8):687–696. https://doi.org/10.1056/NEJMoa1100370
Zhang JY, Zhang F, Hong CQ, Giuliano AE, Cui XJ, Zhou GJ, Zhang GJ, Cui YK (2015) Critical protein GAPDH and its regulatory mechanisms in cancer cells. Cancer Biol Med 12(1):10–22. https://doi.org/10.7497/j.issn.2095-3941.2014.0019
Zhang S, Deng Z, Yao C, Huang P, Zhang Y, Cao S, Li X (2017) AT7867 inhibits human colorectal cancer cells via AKT-dependent and AKT-independent mechanisms. PLoS ONE 12(1):e0169585. https://doi.org/10.1371/journal.pone.0169585
Zhang XH, Wang W, Wang YQ, Jia DF, Zhu L (2018) Human papillomavirus infection and colorectal cancer in the Chinese population: a meta-analysis. Colorec Dis 20(11):961–969. https://doi.org/10.1111/codi.14416
Zhao X, Liu ZP (2019) Analysis of topological parameters of complex disease genes reveals the importance of location in a biomolecular network. Genes. https://doi.org/10.3390/genes10020143
Zhu J, Xu Y, Liu S, Qiao L, Sun J, Zhao Q (2020) MicroRNAs associated with colon cancer: new potential prognostic markers and targets for therapy. Front Bioeng Biotechnol 8:176. https://doi.org/10.3389/fbioe.2020.00176
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors have declared no conflicts of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Khan, A.A. Exploring polyps to colon carcinoma voyage: can blocking the crossroad halt the sequence?. J Cancer Res Clin Oncol 147, 2199–2207 (2021). https://doi.org/10.1007/s00432-021-03685-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-021-03685-5