Document Type : Original Article(s)
Authors
- Saba Dayemomid 1, 2, 3
- Mahan Narjabadifam 4
- Shahin Behrouz Sharif 3
- Shahryar Hashemzadeh 5, 6
- Hossein Samadi Kafil 2
- Amirtaher Eftekharsadat 7
- Ebrahim Sakhinia 1, 3
1 Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
3 Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
4 Department of Genetics, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
5 Department of General and Vascular Surgery, Tabriz University of Medical Sciences, Tabriz, Iran
6 Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
7 Department of Pathology, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
Abstract
Background: Colorectal cancer (CRC) is the third most prevalent cancer with approximately 9,000 annual deaths worldwide. However, early detection can provide a high survival rate. The fecal DNA, as a non-invasive method for detecting the genetic markers, such as the TP53 gene, can be conducive to disease diagnosis. In this study, we aimed to investigate the presence of the TP53 mutations in the stool samples and their relationship with somatic mutations in the tissue samples of CRC patients from northwestern Iran.
Method: In the present cohort study, tumor and stool samples were obtained from 64 CRC patients (mean age of 60), who were undergoing surgery. Total genomic DNA was extracted from the tissue and stool samples, and TP53 mutations were detected using the PCR-SSCP method, followed by direct sequencing. Differences between mutations were observed in the tumors, and the stools were examined using the McNemar method.
Results: Of 64 CRC patients, 19 individuals (30%) demonstrated 27 point mutations in exons 5-7 of the TP53 in the tumor samples. Furthermore, analysis of the stool specimens revealed that the 22 mutations (81.5%) identified in the tumor specimens were also present in the stool of 12 patients (P = 0.063).
Conclusion: Based on the results, the DNA from the tissue could be replaced with fecal DNA in the mutation detections for CRC. Given the non-invasive nature of fecal sampling, it can be desirable and acceptable for patients in molecular screening tests as it increases the screening rates and improves timely CRC diagnosis.
Keywords
How to cite this article:
Dayemomid S, Narjabadifam M, Behrouz Sharif S, Hashemzadeh S, Samadi Kafil H, Eftekharsadat A, et al. Detection of mutations in exons 5, 6, and 7 of the TP53 gene in the tumor tissue and stool samples of patients with colorectal cancer from northwest Iran. Middle East J Cancer. 2022;13(1):34-42. doi: 10.30476/mejc.2021.85284.1267.
2. World Health Organization. Cancer [Internet]. World Health Organization; [Accessed on: 12 September 2018]. Available from: https://www.who.int/news-room/fact-sheets/detail/cancer
3. Li XL, Zhou J, Chen ZR, Chng WJ. P53 mutations in colorectal cancer-molecular pathogenesis and pharmacological reactivation. World J Gastroenterol. 2015;21(1):84. doi:10.3748/wjg.v21.i1.84.
4. Salim EI, Moore MA, Al-Lawati JA, Al-Sayyad J, Bazawir A, Bener A, et al. Cancer epidemiology and control in the arab world-past, present and future. Asian Pac J Cancer Prev. 2009;10(1):3-16.
5. Eser S, Chang J, Charalambous H, Silverman B, Demetriou A, Yakut C, et al. Incidence patterns of colorectal cancers in four countries of the Middle East Cancer Consortium (Cyprus, Jordan, Israel, and Izmir, Turkey) compared with those in the United States Surveillance, Epidemiology, and End Results Program. Turk J Gastroenterol. 2018;29(1):36-44. doi:10. 5152/tjg.2018.17263.
6. Moghimi-Dehkordi B, Safaee A, Zali MR. Prognostic factors in 1,138 Iranian colorectal cancer patients. Int J Colorectal Dis. 2008;23(7):683-8. doi:10.1007/ s00384-008-0463-7.
7. Radmard AR. Five common cancers in Iran. Arch Iran Med. 2010;13(2):143.
8. The American Cancer Society medical and editorial content team. What Causes Colorectal Cancer ? [Internet]. American Cancer Society; 2018 Feb 21 [Last Medical Review: 2020 June 29; Last Revised: 2020 June 29]. Available from: www.cancer.org/cancer/ colon-rectal-cancer/causes-risks-prevention/what-causes.html
9. Armengol G, Sarhadi VK, Ghanbari R, Doghaei-Moghaddam M, Ansari R, Sotoudeh M, et al. Driver gene mutations in stools of colorectal carcinoma patients detected by targeted next-generation sequencing. J Mol Diagn. 2016;18(4):471-9. doi:10. 1016/j.jmoldx.2016.01.008.
10. Ma CX, Guan X, Wang S, Liu Z, Jiang Z, Wang XS. Application and prospect of fecal DNA test in colorectal cancer screening. [In Chinese] Zhonghua Wei Chang Wai Ke Za Zhi. 2019;22(5):491-4. doi:10.3760/ cma.j.issn.1671-0274.2019.05.018.
11. Behrouz Sharif S, Hashemzadeh S, Mousavi Ardehaie R, Eftekharsadat A, Ghojazadeh M, Mehrtash AH, et al. Detection of aberrant methylated SEPT9 and NTRK3 genes in sporadic colorectal cancer patients as a potential diagnostic biomarker. Oncol Lett. 2016;12(6):5335-43. doi:10.3892/ol.2016.5327.
12. Akkiprik M, Ataizi-Celikel C, Dusunceli F, Sonmez O, Gulluodlu BM, Sav A, et al. Clinical significance of p53, K-ras and DCC gene alterations in the stage I-II colorectal cancers. J Gastrointestin Liver Dis. 2007;16(1):11.
13. Bahnassy AA, Zekri AR, Salem SE, Abou-Bakr AA, Sakr MA, Abdel-Samiaa AG, et al. Differential expression of p53 family proteins in colorectal adenomas and carcinomas: Prognostic and predictive values. Histol Histopathol. 2014;29(2):207. doi:10.14670/HH-29.207.
14. Carson DA, Lois A. Cancer progression and p53. Lancet. 1995;346(8981):1009-11. doi:10.1016/s0140-6736(95)91693-8.
15. Rogel A, Popliker M, Webb CG, Oren M. p53 cellular tumor antigen: analysis of mRNA levels in normal adult tissues, embryos, and tumors. Mol Cell Biol. 1985;5(10):2851-5. doi:10.1128/mcb.5.10.2851.
16. Huszno J, Grzybowska E. TP53 mutations and SNPs as prognostic and predictive factors in patients with breast cancer. Oncol Lett. 2018;16(1):34-40. doi:10.3892/ol.2018.8627.
17. Petitjean A, Achatz MI, Borresen-Dale AL, Hainaut P, Olivier M. TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes. Oncogene. 2007;26(15):2157. doi:10.1038/sj.onc.1210302.
18. Shirole NH, Pal D, Kastenhuber ER, Senturk S, Boroda J, Pisterzi P, et al. TP53 exon-6 truncating mutations produce separation of function isoforms with pro-tumorigenic functions. Elife. 2016;5:e17929. doi:10.7554/eLife.17929.
19. Yamashita K, Yoshida T, Shinoda H, Okayasu I. Novel method for simultaneous analysis of p53 and K-ras mutations and p53 protein expression in single histologic sections. Arch Pathol Lab Med. 2001;125(3):347-52. doi:10.1043/0003-9985(2001)125 <0347:NMFSAO>2.0.CO;2.
20. Diez M, Pollán M, Müguerza JM, Gaspar MJ, Duce AM, Alvarez MJ, et al. Time-dependency of the prognostic effect of carcinoembryonic antigen and p53 protein in colorectal adenocarcinoma. Cancer. 2000;88(1):35-41. doi:10.1002/(sici)1097-0142 (20000101)88:1<35::aid-cncr6>3.3.co;2-g.
21. Chang SC, Lin JK, Lin TC, Liang WY. Genetic alteration of p53, but not overexpression of intratumoral p53 protein, or serum p53 antibody is a prognostic factor in sporadic colorectal adenocarcinoma. Int J Oncol. 2005;26(1):65-75. doi:10.3892/ijo.26.1.65.
22. Lam AK, Ong K, Ho YH. hTERT expression in colorectal adenocarcinoma: correlations with p21, p53 expressions and clinicopathological features. Int J Colorectal Dis. 2008;23(6):587-94. doi:10.1007/ s00384-008-0455-7.
23. Nunes BL, Jucá MJ, Gomes EG, Menezes HL, Costa HO, Matos D, et al. Metalloproteinase-1, metalloproteinase-7, and p53 immunoexpression and their correlation with clinicopathological prognostic factors in colorectal adenocarcinoma. Int J Biol Markers. 2009;24(3):156-64. doi:10.5301/jbm.2009.4152.
24. Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science. 1991;253(5015):49-53. doi:10.1126/science.1905840.
25. Golmohammadi R, Namazi MJ, Nikbakht M, Salehi M, Derakhshan MH. Characterization and prognostic value of mutations in exons 5 and 6 of the p53 gene in patients with colorectal cancers in central Iran. Gut Liver. 2013;7(3):295-302. doi:10.5009/gnl.2013. 7.3.295.
26. Nejad AL, Yaghoobi MM. Mutation analysis of TP53 tumor suppressor gene in colorectal cancer in patients from Iran (Kerman Province). Iran J Basic Med Sci. 2012;15(1):683.
27. Leahy DT, Salman R, Mulcahy H, Sheahan K, O'donoghee DP, Parfrey NA. Prognostic significance of p53 abnormalities in colorectal carcinoma detected by PCR–SSCP and immunohistochemical analysis. J Pathol. 1996;180(4):364-70. doi:10.1002/(SICI)1096-9896(199612)180:4<364::AID-PATH683>3.0.CO;2-0.
28. Supek F, Miñana B, Valcárcel J, Gabaldón T, Lehner B. Synonymous mutations frequently act as driver mutations in human cancers. Cell. 2014;156(6):1324-35. doi:10.1016/j.cell.2014.01.051.
29. Chang FH, Tzeng DS, Lung FW, Lee TM, Chen TC, Hsu LS. Mutations in the p53 tumor suppressor gene in colorectal cancer in Taiwan. Kaohsiung J Med Sci. 2003;19(4):151-7. doi:10.1016/S1607-551X(09)70464-4.
30. Piaskowski S, Zawlik I, Szybka M, Kulczycka-Wojdala D, Stoczynska-Fidelus E, Bienkowski M, et al. Detection of P53 mutations in different cancer types is improved by cDNA sequencing. Oncol Lett. 2010;1(4):717-21. doi:10.3892/ol_00000125.
31. Mahdavinia M, Bishehsari F, Verginelli F, Cumashi A, Lattanzio R, Sotoudeh M, et al. P53 mutations in colorectal cancer from northern Iran: Relationships with site of tumor origin, microsatellite instability and K-ras mutations. J Cell Physiol. 2008;216(2):543-50. doi:10.1002/jcp.21428.
32. Mousavi SM, Gouya MM, Ramazani R, Davanlou M, Hajsadeghi N, Seddighi Z. Cancer incidence and mortality in Iran. Ann Oncol. 2008;20(3):556-63. doi:10.1093/annonc/mdn642.
33. Dong SM, Traverso G, Johnson C, Geng L, Favis R, Boynton K, et al. Detecting colorectal cancer in stool with the use of multiple genetic targets. J Natl Cancer Inst. 2001;93(11):858-65. doi:10.1093/jnci/93.11.858.
34. Ghavam-Nasiri MR, Rezaei E, Ghafarzadegan K, Seilanian-Toosi M, Malekifard H. Expression of p53 in colorectal carcinoma: correlation with clinicopathologic features. Arch Iran Med. 2007;10(1):38-42.
35. Wang P, Liang J, Wang Z, Hou H, Shi L, Zhou Z. The prognostic value of p53 positive in colorectal cancer: A retrospective cohort study. Tumor Biology. 2017; 39(5):1010428317703651. doi:10.1177/1010428 317703651.
36. Eguchi S, Kohara N, Komuta K, Kanematsu T. Mutations of the p53 gene in the stool of patients with resectable colorectal cancer. Cancer. 1996;77(8):170. doi:10.1002/(SICI)1097-0142(19960415)77: 8<1707::AID-CNCR43>3.0.CO;2-0.
)