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Yousefisadr, Farzaneh, Mosallaei, Meysam, Sadeghi, Shahryar, Mehrad-Majd, Hassan, Beheshti Namdar, Ali. (1403). MLH1 Methylation-Based Testing in Peripheral Blood Mononuclear Cells is a Promising Biomarker for Colorectal Cancer Diagnosis and Prognosis. سامانه مدیریت نشریات علمی, (), -. doi: 10.30476/mejc.2024.102582.2096
Farzaneh Yousefisadr; Meysam Mosallaei; Shahryar Sadeghi; Hassan Mehrad-Majd; Ali Beheshti Namdar. "MLH1 Methylation-Based Testing in Peripheral Blood Mononuclear Cells is a Promising Biomarker for Colorectal Cancer Diagnosis and Prognosis". سامانه مدیریت نشریات علمی, , , 1403, -. doi: 10.30476/mejc.2024.102582.2096
Yousefisadr, Farzaneh, Mosallaei, Meysam, Sadeghi, Shahryar, Mehrad-Majd, Hassan, Beheshti Namdar, Ali. (1403). 'MLH1 Methylation-Based Testing in Peripheral Blood Mononuclear Cells is a Promising Biomarker for Colorectal Cancer Diagnosis and Prognosis', سامانه مدیریت نشریات علمی, (), pp. -. doi: 10.30476/mejc.2024.102582.2096
Yousefisadr, Farzaneh, Mosallaei, Meysam, Sadeghi, Shahryar, Mehrad-Majd, Hassan, Beheshti Namdar, Ali. MLH1 Methylation-Based Testing in Peripheral Blood Mononuclear Cells is a Promising Biomarker for Colorectal Cancer Diagnosis and Prognosis. سامانه مدیریت نشریات علمی, 1403; (): -. doi: 10.30476/mejc.2024.102582.2096

MLH1 Methylation-Based Testing in Peripheral Blood Mononuclear Cells is a Promising Biomarker for Colorectal Cancer Diagnosis and Prognosis

Middle East Journal of Cancer
مقالات آماده انتشار، پذیرفته شده، انتشار آنلاین از تاریخ 05 شهریور 1403    اصل مقاله (381.34 K)
نوع مقاله: Original Article(s)
شناسه دیجیتال (DOI): 10.30476/mejc.2024.102582.2096
نویسندگان
Farzaneh Yousefisadr1؛ Meysam Mosallaei2؛ Shahryar Sadeghi3؛ Hassan Mehrad-Majd4؛ Ali Beheshti Namdar* 1
1Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
2Medical Biotechnology Research Center, Aja University of Medical Sciences, Tehran, Iran
3Surgical Department, Imam Reza Hospital, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran
4Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
چکیده
Background: Recent evidence has shown that peripheral blood mononuclear cells (PBMCs) can reflect the epigenetic profile of tissues they interact with, such as malignant cells. The hypermethylation of MLH1 promoter is a well-defined epigenetic alteration in the development of colorectal cancer (CRC). This is the first study aimed to assess the diagnostic and prognostic values of the methylation level of MLH1 promoter in PBMCs of patients with CRC.
Method: In this case-control study, the methylation level at the promoter region of MLH1 was quantitatively analyzed in 60 CRC patients and 60 non-cancerous study participants via methylation-quantification of endonuclease-resistant DNA (MethyQESD). The receiver operating characteristic (ROC) curves were constructed and the areas under the curve were calculated to determine the diagnostic significance of MLH1 gene methylation.
Results: Our data showed a significant increase in methylation of MLH1 in CRC patients compared with healthy participants (P < 0.001). Moreover, the specificity of MLH1 hypermethylation for precise diagnosis of healthy participants was 75% and the its sensitivity for CRC diagnosis was 76.7%. With ROC curve analyses, we found that MLH1 promoter methylation holds a likelihood of 76.8% for distinguishing between CRC patients and healthy individuals (P > 0.001). Besides, MLH1 methylation levels was significantly increased in CRC patients with higher tumor stages, suggesting a probable correlation between an increased percentage of methylation and tumor progression (P < 0.001). However, no statistically significant association was found between methylation status of MLH1 and microsatellite instability (P > 0.05).
Conclusion: Our results propose that MLH1 methylation status in PBMCs can be used as a promising diagnostic and prognostic biomarker and reliable factor for CRC screening.

تازه های تحقیق

Farzaneh Yousefisadr (PubMed)

Ali Beheshti Namdar (Google Scholar)

کلیدواژه‌ها
MLH1؛ Colorectal neoplasms؛ Biomarkers؛ Diagnosis
مراجع
  1. Simonian M, Khosravi S, Mortazavi D, Bagheri H, Salehi R, Hassanzadeh A, et al. Environmental risk factors associated with sporadic colorectal cancer in Isfahan, Iran. Middle East J Cancer. 2018;9(4):318-22. doi: 10.30476/mejc.2018.42144.
  2. Zhang Y, Wang Y, Zhang B, Li P, Zhao Y. Methods and biomarkers for early detection, prediction, and diagnosis of colorectal cancer. Biomed Pharmacother. 2023;163:114786. doi: 10.1016/j.biopha.2023.114786. PMID: 37119736.
  3. Pourdavoud P, Pakzad B, Mosallaei M, Saadatian Z, Esmaeilzadeh E, Alimolaie A, et al. MiR-196: emerging of a new potential therapeutic target and biomarker in colorectal cancer. Mol Biol Rep. 2020;47(12):9913-20. doi: 10.1007/s11033-020-05949-8. PMID: 33130965.
  4. Latos W, Aebisher D, Latos M, Krupka-Olek M, Dynarowicz K, Chodurek E, et al. Colonoscopy: Preparation and potential complications. Diagnostics (Basel). 2022;12(3):747. doi: 10.3390/diagnostics12030747. PMID: 35328300; PMCID: PMC8947288.
  5. Fornaro L, Lonardi S, Catanese S, Nappo F, Pietrantonio F, Pellino A, et al. Concordance of microsatellite instability and mismatch repair status in paired biopsies and surgical specimens of resectable gastroesophageal adenocarcinoma: time for a call to action. Gastric Cancer. 2023;26(6):958-68. doi: 10.1007/s10120-023-01411-3. PMID: 37382783.
  6. Wen X, Pu H, Liu Q, Guo Z, Luo D. Circulating tumor DNA-A novel biomarker of tumor progression and its favorable detection techniques. Cancers (Basel). 2022;14(24):6025. doi: 10.3390/cancers14246025. PMID: 36551512; PMCID: PMC9775401.
  7. Symonds EL, Pedersen SK, Murray D, Byrne SE, Roy A, Karapetis C, et al. Circulating epigenetic biomarkers for detection of recurrent colorectal cancer. Cancer. 2020;126(7):1460-9. doi: 10.1002/cncr.32695. PMID: 31909823; PMCID: PMC7155014.
  8. Symonds EL, Pedersen SK, Murray DH, Jedi M, Byrne SE, Rabbitt P, et al. Circulating tumour DNA for monitoring colorectal cancer-a prospective cohort study to assess relationship to tissue methylation, cancer characteristics and surgical resection. Clin Epigenetics. 2018;10:63. doi: 10.1186/s13148-018-0500-5. PMID: 29796114; PMCID: PMC5956533.
  9. Tivey A, Church M, Rothwell D, Dive C, Cook N. Circulating tumour DNA - looking beyond the blood. Nat Rev Clin Oncol. 2022;19(9):600-12. doi: 10.1038/s41571-022-00660-y. PMID: 35915225; PMCID: PMC9341152.
  10. Duffy MJ, Crown J. Circulating tumor DNA as a biomarker for monitoring patients with solid cancers: Comparison with standard protein biomarkers. Clin Chem. 2022;68(11):1381-90. doi: 10.1093/clinchem/hvac121. PMID: 35962648.
  11. Mosallaei M, Ehtesham N, Rahimirad S, Saghi M, Vatandoost N, Khosravi S. PBMCs: a new source of diagnostic and prognostic biomarkers. Arch Physiol Biochem. 2022;128(4):1081-7. doi: 10.1080/13813455.2020.1752257. PMID: 32293207.
  12. Alexovič M, Uličná C, Sabo J, Davalieva K. Human peripheral blood mononuclear cells as a valuable source of disease-related biomarkers: Evidence from comparative proteomics studies. Proteomics Clin Appl. 2024;18(2):e2300072. doi: 10.1002/prca.202300072. PMID: 37933719.
  13. Bagheri H, Mosallaei M, Bagherpour B, Khosravi S, Salehi AR, Salehi R. TFPI2 and NDRG4 gene promoter methylation analysis in peripheral blood mononuclear cells are novel epigenetic noninvasive biomarkers for colorectal cancer diagnosis. J Gene Med. 2020;22(8):e3189. doi: 10.1002/jgm.3189. PMID: 32196834.
  14. Siri G, Mosallaei M, Ehtesham N, Rahimi H, Mazarei M, Nasrollahzadeh Sabet M, et al. TUSC3 methylation in peripheral blood cells as a biomarker for diagnosis of colorectal cancer. Adv Biomed Res. 2023;12:174. doi: 10.4103/abr.abr_396_22. PMID: 37564442; PMCID: PMC10410437.
  15. Shaygannejad A, Sohrabi B, Rad SR, Yousefisadr F, Darvish H, Soosanabadi M. Promoter methylation of matrix metallopeptidase 9 in peripheral blood mononuclear cells: A novel biomarker in a promising source for noninvasive colorectal cancer diagnosis. J Cancer Res Ther. 2023;19(7):1797-802. doi: 10.4103/jcrt.jcrt_2188_21. PMID: 38376281.
  16. Jafarpour S, Saberi F, Yazdi M, Nedaeinia R, Amini G, Ferns GA, et al. Association between colorectal cancer and the degree of ITGA4 promoter methylation in peripheral blood mononuclear cells. Gene Rep. 2022;27:101580. doi:10.1016/j.genrep.2022.101580.
  17. Azhdari S, Khodabandehloo F, Ehtesham N, Mazhari SA, Behroozi J, Siri G. Hypermethylation of MGMT gene promoter in peripheral blood mononuclear cells as a noninvasive biomarker for colorectal cancer diagnosis. Adv Biomed Res. 2023;12:256. doi: 10.4103/abr.abr_206_23. PMID: 38192881; PMCID: PMC10772801.
  18. Mosallaei M, Siri G, Alani B, Khomartash MS, Naghoosi H, Pourghazi F, et al. Differential methylation of DNA promoter sequences in peripheral blood mononuclear cells as promising diagnostic biomarkers for colorectal cancer. J Cancer Res Ther. 2023;10:1-6. doi: 10.4103/jcrt.jcrt_2542_22.
  19. Jung G, Hernández-Illán E, Moreira L, Balaguer F, Goel A. Epigenetics of colorectal cancer: biomarker and therapeutic potential. Nat Rev Gastroenterol Hepatol. 2020;17(2):111-30. doi: 10.1038/s41575-019-0230-y. PMID: 31900466; PMCID: PMC7228650.
  20. Chang SC, Li AF, Lin PC, Lin CC, Lin HH, Huang SC, et al. Clinicopathological and molecular profiles of sporadic microsatellite unstable colorectal cancer with or without the CpG Island Methylator Phenotype (CIMP). Cancers (Basel). 2020;12(11):3487. doi: 10.3390/cancers12113487. PMID: 33238621; PMCID: PMC7700556.
  21. Xu Y, Liu K, Li C, Li M, Zhou X, Sun M, et al. Microsatellite instability in mismatch repair proficient colorectal cancer: clinical features and underlying molecular mechanisms. EBioMedicine. 2024;103:105142. doi: 10.1016/j.ebiom.2024.105142. PMID: 38691939; PMCID: PMC11070601.
  22. Fuss IJ, Kanof ME, Smith PD, Zola H. Isolation of whole mononuclear cells from peripheral blood and cord blood. Curr Protoc Immunol. 2009;Chapter 7:7.1.1-7.1.8. doi: 10.1002/0471142735.im0701s85. PMID: 19347849.
  23. Bettstetter M, Dechant S, Ruemmele P, Vogel C, Kurz K, Morak M, et al. MethyQESD, a robust and fast method for quantitative methylation analyses in HNPCC diagnostics using formalin-fixed and paraffin-embedded tissue samples. Lab Invest. 2008;88(12):1367-75. doi: 10.1038/labinvest.2008.100. PMID: 18936738.
  24. Nam AR, Heo M, Lee KH, Kim JY, Won SH, Cho JY. The landscape of PBMC methylome in canine mammary tumors reveals the epigenetic regulation of immune marker genes and its potential application in predicting tumor malignancy. BMC Genomics. 2023;24(1):403. doi: 10.1186/s12864-023-09471-6. PMID: 37460953; PMCID: PMC10353108.
  25. Kitkumthorn N, Tuangsintanakul T, Rattanatanyong P, Tiwawech D, Mutirangura A. LINE-1 methylation in the peripheral blood mononuclear cells of cancer patients. Clin Chim Acta. 2012;413(9-10):869-74. doi: 10.1016/j.cca.2012.01.024. PMID: 22326975.
  26. Ganapathi SK, Beggs AD, Hodgson SV, Kumar D. Expression and DNA methylation of TNF, IFNG and FOXP3 in colorectal cancer and their prognostic significance. Br J Cancer. 2014;111(8):1581-9. doi: 10.1038/bjc.2014.477. PMID: 25225903; PMCID: PMC4200101.
  27. Parashar S, Cheishvili D, Mahmood N, Arakelian A, Tanvir I, Khan HA, et al. DNA methylation signatures of breast cancer in peripheral T-cells. BMC Cancer. 2018;18(1):574. doi: 10.1186/s12885-018-4482-7. PMID: 29776342; PMCID: PMC5960123.
  28. Shaygannejad A, Sohrabi B, Rad SR, Yousefisadr F, Darvish H, Soosanabadi M. Promoter methylation of matrix metallopeptidase 9 in peripheral blood mononuclear cells: A novel biomarker in a promising source for noninvasive colorectal cancer diagnosis. J Cancer Res Ther. 2023;19(7):1797-802. doi: 10.4103/jcrt.jcrt_2188_21. PMID: 38376281.
  29. Boonsongserm P, Angsuwatcharakon P, Puttipanyalears C, Aporntewan C, Kongruttanachok N, Aksornkitti V, et al. Tumor-induced DNA methylation in the white blood cells of patients with colorectal cancer. Oncol Lett. 2019;18(3):3039-48. doi: 10.3892/ol.2019.10638. PMID: 31452782; PMCID: PMC6676401.
  30. Friso S, Udali S, Guarini P, Pellegrini C, Pattini P, Moruzzi S, et al. Global DNA hypomethylation in peripheral blood mononuclear cells as a biomarker of cancer risk. Cancer Epidemiol Biomarkers Prev. 2013;22(3):348-55. doi: 10.1158/1055-9965.EPI-12-0859. PMID: 23300023; PMCID: PMC3596466.
  31. Chen Z, Zhao G, Wang K, Wang X, Ma Y, Xiong S, et al. Blood leukocytes methylation levels analysis indicate methylated plasma test is a promising tool for colorectal cancer early detection. J Cancer. 2021;12(12):3678-85. doi: 10.7150/jca.57114. PMID: 33995643; PMCID: PMC8120172.
  32. Elashi AA, Sasidharan Nair V, Taha RZ, Shaath H, Elkord E. DNA methylation of immune checkpoints in the peripheral blood of breast and colorectal cancer patients. Oncoimmunology. 2018;8(2):e1542918. doi: 10.1080/2162402X.2018.1542918. PMID: 30713804; PMCID: PMC6343790.
  33. Wang SM, Jiang B, Deng Y, Huang SL, Fang MZ, Wang Y. Clinical significance of MLH1/MSH2 for stage II/III sporadic colorectal cancer. World J Gastrointest Oncol. 2019;11(11):1065-80. doi: 10.4251/wjgo.v11.i11.1065. PMID: 31798786; PMCID: PMC6883179.
  34. Jasmine F, Haq Z, Kamal M, Raza M, da Silva G, Gorospe K, et al. Interaction between microsatellite instability (MSI) and tumor DNA methylation in the pathogenesis of colorectal carcinoma. Cancers (Basel). 2021;13(19):4956. doi: 10.3390/cancers13194956. PMID: 34638440; PMCID: PMC8508563.
  35. Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487(7407):330-7. doi: 10.1038/nature11252. PMID: 22810696; PMCID: PMC3401966.
  36. Kumar K, Brim H, Giardiello F, Smoot DT, Nouraie M, Lee EL, et al. Distinct BRAF (V600E) and KRAS mutations in high microsatellite instability sporadic colorectal cancer in African Americans. Clin Cancer Res. 2009;15(4):1155-61. doi: 10.1158/1078-0432.CCR-08-1029. PMID: 19190129; PMCID: PMC2713502.
  37. Ma Y, Chen Y, Petersen I. Expression and promoter DNA methylation of MLH1 in colorectal cancer and lung cancer. Pathol Res Pract. 2017;213(4):333-8. doi: 10.1016/j.prp.2017.01.014. PMID: 28214209.
  38. Tan X, Fang Y, Fan X, Deng W, Huang J, Cai Y, et al. Testing region selection and prognostic analysis of MLH1 promoter methylation in colorectal cancer in China. Gastroenterol Rep (Oxf). 2024;12:goae011. doi: 10.1093/gastro/goae011. PMID: 38566849; PMCID: PMC10985700.
  39. Li X, Yao X, Wang Y, Hu F, Wang F, Jiang L, et al. MLH1 promoter methylation frequency in colorectal cancer patients and related clinicopathological and molecular features. PLoS One. 2013;8(3):e59064. doi: 10.1371/journal.pone.0059064. PMID: 23555617; PMCID: PMC3612054.
  40. Gausachs M, Mur P, Corral J, Pineda M, González S, Benito L, et al. MLH1 promoter hypermethylation in the analytical algorithm of Lynch syndrome: a cost-effectiveness study. Eur J Hum Genet. 2012;20(7):762-8. doi: 10.1038/ejhg.2011.277. PMID: 22274583; PMCID: PMC3376264.
  41. Li Q, Hong J, Shen Z, Deng H, Shen Y, Wu Z, et al. A systematic review and meta-analysis approach on diagnostic value of MLH1 promoter methylation for head and neck squamous cell carcinoma. Medicine (Baltimore). 2019;98(43):e17651. doi: 10.1097/MD.0000000000017651. PMID: 31651887; PMCID: PMC6824735.
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