Ten-Year Recurrence Outcomes in Early Stage and Early Onset Colon Cancer and the Expression Profiles of MicroRNAs and Cancer Stem Cell Markers in These Tumors

Öz:

Objective: We hypothesized that microRNAs (miRNAs) might be involved in tumor development by critically regulating cancer stem cell (CSC) markers in the early stages of colon cancer (eCC). This study aimed to determine the expression profiles of miRNAs in CSC-positive eCC patients and examine their associations with recurrence. Materials and Methods: We analyzed CD133, LGR5 and SOX2 expression profiles to determine CSC status in 30 eCC specimens. Then, using the results of RT2 miRNA PCR custom arrays, we evaluated the expression profiles of 38 miRNAs in CSC-positive eCC patients. Results: Recurrence occurred in 5 patients within ten years after surgery. We determined down-regulation of miR-125b and up-regulation of miR-135b were significant in CSC-positive eCC patients (p=0.021, p=0.001, respectively). We found that low expression of miR-125b was associated with recurrence in eCC (p=0.0022). Conclusions: We suggest that recurrence might be prevented by increasing the expression of miR-125b in eCC.

Anahtar Kelime: cancer stem cell colon cancer early-onset early-stage microRNA

Erken Evre Kolon Kanserinde On Yıllık Nüks Sonuçları ve Bu Tümörlerde MikroRNA'ların ve Kanser Kök Hücre Belirteçlerinin Ekspresyon Profilleri

Öz:

Amaç: MikroRNA'ların (miRNA'lar), kolon kanserinin erken evrelerinde (eCC) kanser kök hücre (CSC) belirteçlerini kritik olarak düzenleyerek tümör gelişiminde rol oynayabileceğini varsaydık. Bu çalışmanın amacı, CSC pozitif eCC hastalarında miRNA'ların ekspresyon profillerini belirlemek ve nüks ile ilişkilerini incelemektir. Materyal ve Metot: 30 eCC örneğinde CSC durumunu belirlemek için CD133, LGR5 ve SOX2 ekspresyon profillerini analiz ettik. Ardından, RT2 miRNA PCR özel dizilerinin sonuçlarını kullanarak, CSC pozitif eCC hastalarında 38 miRNA'nın ekspresyon profillerini değerlendirdik. Bulgular: Ameliyattan sonraki 10 yıl içinde 5 hastada nüks meydana geldi. CSC pozitif eCC hastalarında miR-125b'nin aşağı regülasyonunun ve miR-135b'nin yukarı regülasyonunun anlamlı olduğunu belirledik (sırasıyla p=0,21, p=0,001). miR-125b'nin düşük ifadesinin eCC'de tekrarlama ile ilişkili olduğunu bulduk (p=0,0022). Sonuç: eCC'de miR-125b ekspresyonunun arttırılmasıyla nüksün önlenebileceğini düşünüyoruz.

Anahtar Kelime: Erken başlangıçlı erken evre kanser kök hücresi kolon kanseri mikroRNA

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Patel SG, Ahnen DJ. Colorectal Cancer in the Young. Curr Gastroenterol Rep. 2018;20:15. doi:10.1007/s11894-018-0618-9
2. Tezcan G, Tunca B, Ak S, Cecener G, Egeli U. Molecular approach to genetic and epigenetic pathogenesis of early-onset colorectal cancer. World J Gastrointest Oncol. 2016;8:83-98. doi:10.4251/wjgo.v8.i1.83
3. Chowdhury F, Huang B, Wang N. Forces in stem cells and cancer stem cells. Cells Dev. 2022;25:203776. doi:10.1016/j.cdev.2022.203776
4. Ozturk E, Aksoy SA, Ugras N, et al. Coexistence of MACC1 and NM23-H1 dysregulation and tumor budding promise early prognostic evidence for recurrence risk of early-stage colon cancer. APMIS. 2018;126:99-108. doi:10.1111/apm.12801
5. Mukohyama J, Shimono Y, Minami H, Kakeji Y, Suzuki A. Roles of microRNAs and RNA-Binding Proteins in the Regulation of Colorectal Cancer Stem Cells. Cancers (Basel). 2017;9:143. doi:10.3390/cancers9100143
6. Wang K, Song W, Shen Y, Wang H, Fan Z. LncRNA KLK8 modulates stem cell characteristics in colon cancer. Pathol Res Pract. 2021;224:153437. doi:10.1016/j.prp.2021.153437.
7. Stark VA, Facey COB, Viswanathan V, Boman BM. The Role of miRNAs, miRNA Clusters, and isomiRs in Development of Cancer Stem Cell Populations in Colorectal Cancer. Int J Mol Sci. 2021;22(3):1424. doi:10.3390/ijms22031424.
8. Iwasaki H, Shimura T, Kitagawa M, et al. A Novel Urinary miRNA Biomarker for Early Detection of Colorectal Cancer Cancers (Basel). 2022;14(2):461. doi:10.3390/cancers14020461
9. Radanova M, Levkova M, Mihaylova G, et al. Single Nucleotide Polymorphisms in microRNA Genes and Colorectal Cancer Risk and Prognosis. Biomedicines. 2022;10(1):156. doi:10.3390/biomedicines10010156
10. Shimono Y, Zabala M, Cho RW, et al. Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell. 2009;138:592-603. doi:10.1016/j.cell.2009.07.011
11. Lai S, Cheng R, Gao D, Chen YG, Deng C. LGR5 constitutively activates NF-κB signaling to regulate the growth of intestinal crypts. FASEB J. 2020;34(11):15605-15620. doi:10.1096/fj.202001329R
12. Abdel Mageed M, Ismail HTH, Olsson L, et al. Clinical Significance of Stem Cell Biomarkers EpCAM, LGR5 and LGR4 mRNA Levels in Lymph Nodes of Colon Cancer Patients. Int J Mol Sci. 2021;23(1):403. doi:10.3390/ijms23010403
13. Abdelrahman AE, El-Azony A, Elsebai E, Ibrahim HM. Prognostic Impact of LGR5, Prox1, and Notch1 Biomarkers in Stage II to III Colon Cancer. Appl Immunohistochem Mol Morphol. 2022;30(2):126-135. doi:10.1097/PAI.0000000000000983.
14. Neumann J, Bahr F, Horst D, et al. SOX2 expression correlates with lymph-node metastases and distant spread in right-sided colon cancer. BMC Cancer. 2011;518. doi:10.1186/1471-2407-11-518
15. Stark VA, Facey COB, Viswanathan V, Boman BM. The Role of miRNAs, miRNA Clusters, and isomiRs in Development of Cancer Stem Cell Populations in Colorectal Cancer. Int J Mol Sci. 2021;22(3):1424. doi:10.3390/ijms22031424
16. 16.Hisamori S, Mukohyama J, Koul S, et al. Upregulation of BMI1-suppressor miRNAs (miR-200c, miR-203) during terminal differentiation of colon epithelial cells. J Gastroenterol. 2022;4. doi:10.1007/s00535-022-01865-9
17. Ebrahimi N, Rezanejad H, Asadi MH, Vallian S. LncRNA LOC100507144 acts as a novel regulator of CD44/Nanog/Sox2/miR-302/miR-21 axis in colorectal cancer. Biofactors. 2022;48(1):164-180. doi:10.1002/biof.1813
18. Zhang J, Yang W, Xiao Y, Shan L. MiR-125b Inhibits Cell Proliferation and Induces Apoptosis in Human Colon Cancer SW480 Cells via Targeting STAT3. Recent Pat Anticancer Drug Discov. 2022. doi:10.2174/1574892816666210708165037.
19. Yu Y, Nangia-Makker P, Farhana L, Rajendra GS, Levi E, Majumdar AP. miR-21 and miR-145 cooperation in regulation of colon cancer stem cells. Mol Cancer. 2015;14:98. doi:10.1186/s12943-015-0372-7
20. Li L, Wang A, Cai M, Tong M, Chen F, Huang L. Identification of stool miR-135b-5p as a non-invasive diaognostic biomarker in later tumor stage of colorectal cancer. Life Sci. 2020;1;260:118417. doi:10.1016/j.lfs.2020.118417
21. Zhang Y, Wang Y, Guo Y, Liao Z, Xu R, Ruan Z. miR-135b promotes the invasion and metastasis of hepatocellular carcinoma cells. 2015;31(10):1316-1321.
22. Akbari A, Ghahremani MH, Mobini GR, Abastabar M, Akhtari J, Bolhassani M, Heidari M. Down-regulation of miR-135b in colon adenocarcinoma induced by a TGF-β receptor I kinase inhibitor. Iran J Basic Med Sci. 2015;18(9):856–861.
23. Ak S, Tunca B, Tezcan G, et al. MicroRNA expression patterns of tumors in early-onset colorectal cancer patients. J Surg Res. 2014;191(1):113-22. doi:10.1016/j.jss.2014.03.057
24. Chen H, Xu Z. Hypermethylation-Associated Silencing of miR-125a and miR-125b: A Potential Marker in Colorectal Cancer. Dis Markers. 2015;2015:345080. doi:10.1155/2015/345080
25. Fujino Y, Takeishi S, Nishida K, et al. Downregulation of microRNA-100/microRNA-125b is associated with lymph node metastasis in early colorectal cancer with submucosal invasion. Cancer Sci. 2017;108:390-397. doi:10.1111/cas.13152
26. Nishida N, Yokobori T, Mimori K, et al. miR-125b is a prognostic marker in human colorectal cancer. Int J Oncol. 2011;38(5):1437-1443. doi:10.3892/ijo.2011.969
27. Sui M, Jiao A, Zhai H, et al. Upregulation of miR-125b is associated with poor prognosis and trastuzumab resistance in HER2-positive gastric cancer. Exp Ther Medical. 2017;14(1):657–663. doi:10.3892/etm.2017.4548
28. Amiri-Dashatan N, Koushki M, Naghi-Zadeh M, Razzaghi MR, Mohaghegh Shalmani H. Prognostic value of microRNA-125a/b family in patients with gastric cancer: a meta-analysis. Gastroenterol Hepatol Bed Bench. 2021;14(Suppl1):S1-S9.
29. He X, Liao S, Lu D, Zhang F, Sun Y, Wu Y. MiR-125b promotes migration and invasion by targeting the vitamin D receptor in renal cell carcinoma. Int J Med Sci. 2021;18(1):150-156. doi:10.7150/ijms.49328
30. Zhou JN, Zeng Q, Wang HY, et al. MicroRNA-125b attenuates epithelial-mesenchymal transitions and targets stem-like liver cancer cells through small mothers against decapentaplegic 2 and 4. Hepatology. 2015;62(3):801-815. doi:10.1002/hep.27887

APA	Aksoy S, Tunca B, Yılmazlar T, Isik O, Ozturk E, Ercelik m, Tekin C, Gulcu B, Ugras N, Yerci Ö, Cecener G, Egeli U (2023). Ten-Year Recurrence Outcomes in Early Stage and Early Onset Colon Cancer and the Expression Profiles of MicroRNAs and Cancer Stem Cell Markers in These Tumors. , 16 - 23. 10.26453/otjhs.1074644
Chicago	Aksoy Seçil,Tunca Berrin,Yılmazlar Tuncay,Isik Ozgen,Ozturk Ersin,Ercelik melis,Tekin Cagla,Gulcu Baris,Ugras Nesrin,Yerci Ömer,Cecener Gulsah,Egeli Unal Ten-Year Recurrence Outcomes in Early Stage and Early Onset Colon Cancer and the Expression Profiles of MicroRNAs and Cancer Stem Cell Markers in These Tumors. (2023): 16 - 23. 10.26453/otjhs.1074644
MLA	Aksoy Seçil,Tunca Berrin,Yılmazlar Tuncay,Isik Ozgen,Ozturk Ersin,Ercelik melis,Tekin Cagla,Gulcu Baris,Ugras Nesrin,Yerci Ömer,Cecener Gulsah,Egeli Unal Ten-Year Recurrence Outcomes in Early Stage and Early Onset Colon Cancer and the Expression Profiles of MicroRNAs and Cancer Stem Cell Markers in These Tumors. , 2023, ss.16 - 23. 10.26453/otjhs.1074644
AMA	Aksoy S,Tunca B,Yılmazlar T,Isik O,Ozturk E,Ercelik m,Tekin C,Gulcu B,Ugras N,Yerci Ö,Cecener G,Egeli U Ten-Year Recurrence Outcomes in Early Stage and Early Onset Colon Cancer and the Expression Profiles of MicroRNAs and Cancer Stem Cell Markers in These Tumors. . 2023; 16 - 23. 10.26453/otjhs.1074644
Vancouver	Aksoy S,Tunca B,Yılmazlar T,Isik O,Ozturk E,Ercelik m,Tekin C,Gulcu B,Ugras N,Yerci Ö,Cecener G,Egeli U Ten-Year Recurrence Outcomes in Early Stage and Early Onset Colon Cancer and the Expression Profiles of MicroRNAs and Cancer Stem Cell Markers in These Tumors. . 2023; 16 - 23. 10.26453/otjhs.1074644
IEEE	Aksoy S,Tunca B,Yılmazlar T,Isik O,Ozturk E,Ercelik m,Tekin C,Gulcu B,Ugras N,Yerci Ö,Cecener G,Egeli U "Ten-Year Recurrence Outcomes in Early Stage and Early Onset Colon Cancer and the Expression Profiles of MicroRNAs and Cancer Stem Cell Markers in These Tumors." , ss.16 - 23, 2023. 10.26453/otjhs.1074644
ISNAD	Aksoy, Seçil vd. "Ten-Year Recurrence Outcomes in Early Stage and Early Onset Colon Cancer and the Expression Profiles of MicroRNAs and Cancer Stem Cell Markers in These Tumors". (2023), 16-23. https://doi.org/10.26453/otjhs.1074644

APA	Aksoy S, Tunca B, Yılmazlar T, Isik O, Ozturk E, Ercelik m, Tekin C, Gulcu B, Ugras N, Yerci Ö, Cecener G, Egeli U (2023). Ten-Year Recurrence Outcomes in Early Stage and Early Onset Colon Cancer and the Expression Profiles of MicroRNAs and Cancer Stem Cell Markers in These Tumors. Online Türk Sağlık Bilimleri Dergisi, 8(1), 16 - 23. 10.26453/otjhs.1074644
Chicago	Aksoy Seçil,Tunca Berrin,Yılmazlar Tuncay,Isik Ozgen,Ozturk Ersin,Ercelik melis,Tekin Cagla,Gulcu Baris,Ugras Nesrin,Yerci Ömer,Cecener Gulsah,Egeli Unal Ten-Year Recurrence Outcomes in Early Stage and Early Onset Colon Cancer and the Expression Profiles of MicroRNAs and Cancer Stem Cell Markers in These Tumors. Online Türk Sağlık Bilimleri Dergisi 8, no.1 (2023): 16 - 23. 10.26453/otjhs.1074644
MLA	Aksoy Seçil,Tunca Berrin,Yılmazlar Tuncay,Isik Ozgen,Ozturk Ersin,Ercelik melis,Tekin Cagla,Gulcu Baris,Ugras Nesrin,Yerci Ömer,Cecener Gulsah,Egeli Unal Ten-Year Recurrence Outcomes in Early Stage and Early Onset Colon Cancer and the Expression Profiles of MicroRNAs and Cancer Stem Cell Markers in These Tumors. Online Türk Sağlık Bilimleri Dergisi, vol.8, no.1, 2023, ss.16 - 23. 10.26453/otjhs.1074644
AMA	Aksoy S,Tunca B,Yılmazlar T,Isik O,Ozturk E,Ercelik m,Tekin C,Gulcu B,Ugras N,Yerci Ö,Cecener G,Egeli U Ten-Year Recurrence Outcomes in Early Stage and Early Onset Colon Cancer and the Expression Profiles of MicroRNAs and Cancer Stem Cell Markers in These Tumors. Online Türk Sağlık Bilimleri Dergisi. 2023; 8(1): 16 - 23. 10.26453/otjhs.1074644
Vancouver	Aksoy S,Tunca B,Yılmazlar T,Isik O,Ozturk E,Ercelik m,Tekin C,Gulcu B,Ugras N,Yerci Ö,Cecener G,Egeli U Ten-Year Recurrence Outcomes in Early Stage and Early Onset Colon Cancer and the Expression Profiles of MicroRNAs and Cancer Stem Cell Markers in These Tumors. Online Türk Sağlık Bilimleri Dergisi. 2023; 8(1): 16 - 23. 10.26453/otjhs.1074644
IEEE	Aksoy S,Tunca B,Yılmazlar T,Isik O,Ozturk E,Ercelik m,Tekin C,Gulcu B,Ugras N,Yerci Ö,Cecener G,Egeli U "Ten-Year Recurrence Outcomes in Early Stage and Early Onset Colon Cancer and the Expression Profiles of MicroRNAs and Cancer Stem Cell Markers in These Tumors." Online Türk Sağlık Bilimleri Dergisi, 8, ss.16 - 23, 2023. 10.26453/otjhs.1074644
ISNAD	Aksoy, Seçil vd. "Ten-Year Recurrence Outcomes in Early Stage and Early Onset Colon Cancer and the Expression Profiles of MicroRNAs and Cancer Stem Cell Markers in These Tumors". Online Türk Sağlık Bilimleri Dergisi 8/1 (2023), 16-23. https://doi.org/10.26453/otjhs.1074644