Multi-stage analysis of FOXM1, PYROXD1, hTERT, PPARA, PIM3, BMI1 and MCTP1 expression patterns in colorectal cancer
Gastroenterology and Hepatology from Bed to Bench,
Vol. 15 No. 2 (2022),
15 March 2022
https://doi.org/10.22037/ghfbb.vi.2304
Abstract
Aim: To explore biomarkers with a tumor stage-dependent expression pattern in patients with colorectal cancer (CRC).
Background: The fourth most common cancer in the world is colorectal cancer (CRC). A variation in the gene expression rate is a common change in cancers initiation and the accumulation of these variation changes the behavior of normal cells and turns them into cancer cells.
Methods: Real-time RT-PCR was used to investigate the expression patterns of the FOXM1, PYROXD1, hTERT, BMI, PPARA, PIM3 and MCTP1 genes in 54 patients with stage I to IV CRC and their relation with clinicopathological features of CRC were analyzed. Results: FOXM1, hTERT and MCTP1 genes are overexpressed in CRC tumor tissues when compared to normal adjacent tissues in all the stages.
Results FOXM1, PYROXD1, hTERT, PIM3, BMI1, PPARA and MCTP1 had-stage dependent expression. Investigation of the association between clinicopathological features and expression pattern of the studied genes revealed; a) a significant relationship between FOXM1 gene expression level and tumor stage, tumor size and lymph node involvement, b) a considerable association between alterations in PPARA and PIM3 expression and lymph node involvement, c) a notable correlation between hTERT expression level and the tumor stage and d) a strong correlation between MCTP1 expression and patient's age only.
Conclusion: Our study indicates that expression profiles of these genes either individually or together can be applied as potential biomarkers for prognosis of CRC.
- Colorectal cancer
- Expression pattern
- Real-time RT-PCR
How to Cite
References
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359-86.
Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut 2017; 66:683-91.
Sadjadi A, Nouraie M, Mohagheghi MA, Mousavi-Jarrahi A, Malekezadeh R, Parkin DM. Cancer occurrence in Iran in 2002, an international perspective. Asian Pac J Cancer Prev 2005;6:359-63.
Motalebzadeh J, Shabani S, Rezayati S, Shakournia N, Mirzaei R, Mahjoubi B, et al. Prognostic Value of FBXO39 and ETS-1 but not BMI-1 in Iranian Colorectal Cancer Patients. Asian Pac J Cancer Prev 2018;19:1357-1362.
Yari H, Shabani S, Nafissi N, Majidzadeh T, Mahjoubi F. Investigation of promoter methylation patterns association with genes expression profile of ISL1, MGMT and DMNT3b in tissue of breast cancer patients. Mol Biol Rep 2022;49:847-857.
Ohori M, Wheeler TM, Scardino PT. The New American Joint Committee on Cancer and International Union against Cancer TNM classification of prostate cancer. Clinicopathologic correlations. Cancer 1994;74:104-14.
Sarver AL, French AJ, Borralho PM, Thayanithy V, Oberg AL, Silverstein KA, et al. Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states. BMC Cancer 2009;9:401.
Biller LH, Schrag D. Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. JAMA 2021;325:669-85.
Lepourcelet M, Tou L, Cai L, Sawada J, Lazar AJ, Glickman JN, et al. Insights into developmental mechanisms and cancers in the mammalian intestine derived from serial analysis of gene expression and study of the hepatoma-derived growth factor (HDGF). Development 2005;132:415-27.
Cohen R, Pudlarz T, Delattre JF, Colle R, André T. Molecular Targets for the Treatment of Metastatic Colorectal Cancer. Cancers (Basel) 2020;12:2350.
Maak M, Simon I, Nitsche U, Roepman P, Snel M, Glas AM, et al. Independent validation of a prognostic genomic signature (ColoPrint) for patients with stage II colon cancer. Ann Surg 2013;257:1053-8.
Sobin LH, Compton CC. TNM seventh edition: what's new, what's changed: communication from the International Union against Cancer and the American Joint Committee on Cancer? Cancer 2010;116:5336-9.
Mahmodlou R, Mohammadi P, Sepehrvand N. Colorectal cancer in northwestern Iran. ISRN Gastroenterol 2012;2012:968560.
Tavakoli Koudehi A, Mahjoubi B, Mirzaei R, Shabani S, Mahjoubi F. AKAP4, SPAG9 and NY-ESO-1 in Iranian Colorectal Cancer Patients as Probable Diagnostic and Prognostic Biomarkers. Asian Pac J Cancer Prev 2018;19:463-469.
Eschrich S, Yang I, Bloom G, Kwong KY, Boulware D, Cantor A, Coppola D, Kruhøffer M, Aaltonen L, Orntoft TF, Quackenbush J, Yeatman TJ. Molecular staging for survival prediction of colorectal cancer patients. J Clin Oncol 2005;23:3526-35.
Nannini M, Pantaleo MA, Maleddu A, Astolfi A, Formica S, Biasco G. Gene expression profiling in colorectal cancer using microarray technologies: results and perspectives. Cancer Treat Rev 2009;35:201-9.
Shabani S, Samanian S, Mirzaei R, Mahjoubi B, Mahjoubi F. Correlation among MDR1, MRP and hTERT Genes Expression Level and Clinical Response in Colorectal Cancer Patients. J Mol Biomarkers Diagn 2014;5:1.
Shabani S, Khayer N, Motalebzadeh J, Majidi Zadeh T, Mahjoubi F. Characterization of pathways involved in colorectal cancer using real-time RT-PCR gene expression data. Gastroenterol Hepatol Bed Bench 2021;14:123-31.
Wierstra I, Alves J. FOXM1, a typical proliferation-associated transcription factor. Biol Chem 2007;388:1257-74.
Sun HL, Men JR, Liu HY, Liu MY, Zhang HS. FOXM1 facilitates breast cancer cell stemness and migration in YAP1-dependent manner. Arch Biochem Biophys 2020;685:108349.
Kalin TV, Ustiyan V, Kalinichenko VV. Multiple faces of FoxM1 transcription factor: lessons from transgenic mouse models. Cell Cycle 2011;10:396-405.
Koo CY, Muir KW, Lam EW. FOXM1: From cancer initiation to progression and treatment. Biochim Biophys Acta 2012;1819:28-37.
Huang C, Du J, Xie K. FOXM1 and its oncogenic signaling in pancreatic cancer pathogenesis. Biochim Biophys Acta 2014;1845:104-16.
Zhang Z, Tu K, Liu F, Liang M, Yu K, Wang Y, et al. FoxM1 promotes the migration of ovarian cancer cell through KRT5 and KRT7. Gene 2020;757:144947.
Zhang J, Zhang K, Zhou L, Wu W, Jiang T, Cao J, et al. Expression and potential correlation among Forkhead box protein M1, Caveolin-1 and E-cadherin in colorectal cancer. Oncol Lett 2016;12:2381-2388.
Chu XY, Zhu ZM, Chen LB, Wang JH, Su QS, Yang JR, et al. FOXM1 expression correlates with tumor invasion and a poor prognosis of colorectal cancer. Acta Histochem 2012;114:755-62.
Bellelli R, Castellone MD, Garcia-Rostan G, Ugolini C, Nucera C, Sadow PM, et al. FOXM1 is a molecular determinant of the mitogenic and invasive phenotype of anaplastic thyroid carcinoma. Endocr Relat Cancer 2012;19:695-710.
Sher T, Yi HF, McBride OW, Gonzalez FJ. cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor. Biochemistry 1993; 32:5598-604.
Michalik L, Desvergne B, Wahli W. Peroxisome-proliferator-activated receptors and cancers: complex stories. Nat Rev Cancer 2004;4:61-70.
Luo Y, Xie C, Brocker CN, Fan J, Wu X, Feng L, et al. Intestinal PPARα Protects Against Colon Carcinogenesis via Regulation of Methyltransferases DNMT1 and PRMT6. Gastroenterology 2019;157:744-59.
Rakhshandehroo M, Sanderson LM, Matilainen M, Stienstra R, Carlberg C, de Groot PJ, et al. Comprehensive analysis of PPARalpha-dependent regulation of hepatic lipid metabolism by expression profiling. PPAR Res 2007;2007:26839.
Sanderson LM, de Groot PJ, Hooiveld GJ, Koppen A, Kalkhoven E, Müller M, et al. Effect of synthetic dietary triglycerides: a novel research paradigm for nutrigenomics. PLoS One 2008;3:e1681.
Tan IB, Tan P. Genetics: an 18-gene signature (ColoPrint®) for colon cancer prognosis. Nat Rev Clin Oncol 2011;8:131-3.
Nakamura TM, Morin GB, Chapman KB, Weinrich SL, Andrews WH, Lingner J, et al. Telomerase catalytic subunit homologs from fission yeast and human. Science 1997;277:955-59.
Bertorelle R, Briarava M, Rampazzo E, Biasini L, Agostini M, Maretto I, et al. Telomerase is an independent prognostic marker of overall survival in patients with colorectal cancer. Br J Cancer 2013;108:278-84.
Argyrou A, Blanchard JS. Flavoprotein disulfide reductases: advances in chemistry and function. Prog Nucleic Acid Res Mol Biol 2004;78:89-142.
Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 2010;49:1603-16.
Shabani S, Mahjoubi F, Moosavi MA. A siRNA-based method for efficient silencing of PYROXD1 gene expression in the colon cancer cell line HCT116. J Cell Biochem 2019;120:19310-19317.
Mukaida N, Wang YY, Li YY. Roles of Pim-3, a novel survival kinase, in tumorigenesis. Cancer Sci 2011;102:1437-42.
Zhou Y, Zhou YN, Liu SX, Wang J, Ji R, Yan X. Effects of PIM3 in prognosis of colon cancer. Clin Transl Oncol 2021;23:2163-2170.
Zheng HC, Tsuneyama K, Takahashi H, Miwa S, Sugiyama T, Popivanova BK, et al. Aberrant Pim-3 expression is involved in gastric adenoma-adenocarcinoma sequence and cancer progression. J Cancer Res Clin Oncol 2008;134:481-88.
Popivanova BK, Li YY, Zheng H, Omura K, Fujii C, Tsuneyama K, et al. Proto-oncogene, Pim-3 with serine/threonine kinase activity, is aberrantly expressed in human colon cancer cells and can prevent Bad-mediated apoptosis. Cancer Sci 2007;98:321-28.
Li YY, Popivanova BK, Nagai Y, Ishikura H, Fujii C, Mukaida N. Pim-3, a proto-oncogene with serine/threonine kinase activity, is aberrantly expressed in human pancreatic cancer and phosphorylates bad to block bad-mediated apoptosis in human pancreatic cancer cell lines. Cancer Res 2006;66:6741-47.
Zhu S, Zhao D, Yan L, Jiang W, Kim JS, Gu B, et al. BMI1 regulates androgen receptor in prostate cancer independently of the polycomb repressive complex 1. Nat Commun 2018;9:500.
Lessard J, Sauvageau G. Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature 2003;423:255-60.
Jia L, Zhang W, Wang CY. BMI1 Inhibition Eliminates Residual Cancer Stem Cells after PD1 Blockade and Activates Antitumor Immunity to Prevent Metastasis and Relapse. Cell Stem Cell 2020;27:238-53.
Gray F, Cho HJ, Shukla S, He S, Harris A, Boytsov B, et al. BMI1 regulates PRC1 architecture and activity through homo- and hetero-oligomerization. Nat Commun 2016;7:13343.
Zhu S, Zhao D, Li C, Li Q, Jiang W, Liu Q, et al. BMI1 is directly regulated by androgen receptor to promote castration-resistance in prostate cancer. Oncogene 2020;39:17-29.
Shin OH, Han W, Wang Y, Südhof TC. Evolutionarily conserved multiple C2 domain proteins with two transmembrane regions (MCTPs) and unusual Ca2+ binding properties. J Biol Chem 2005;280:1641-51.
Berridge MJ, Lipp P, Bootman MD. The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 2000;1:11-21.
Kong L, Yang W, Chen L, Qian L. The DNA methylation-regulated MCTP1 activates the drug-resistance of esophageal cancer cells. Aging (Albany NY) 2021;13:3342-3352.
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