IMMUNOHISTOCHEMICAL STUDY OF CD44 AND OCT3/4 EXPRESSION IN COLORECTAL CANCER SAMPLES OF IRAQI PATIENTS
DOI:
https://doi.org/10.15407/exp-oncology.2025.01.044Keywords:
cancer stem cells, biomarkers, colorectal cancer, CD44, OCT3/4, immunostainingAbstract
Background. Colorectal cancer (CRC) is one of the most common cancer types diagnosed globally with high rates of morbidity and mortality. Several biomarkers are associated with cancer stem cells present in various solid tumors, including CRC. Aim. This study aimed to investigate the expression of CD44 and OCT3/4 cancer stem cell markers in samples of CRC biopsies and benign colon tumors of Iraqi patients using the immunohistochemical (IHC) technique. Materials and Methods. The IHC analysis was used to determine CD44 and OCT3/4 expression levels in tissue samples of 42 CRC cases and 18 benign neoplasms. Results. The findings revealed a significant increase in high expression levels of CD44 in CRC cases (81%) vs 23% in benign tumor tissue samples. Similarly, a significant rise in OCT3/4 expression was observed in CRC cases (66%) compared to benign tumors (29%). The expression levels of CD44 and OCT3/4 were significantly associated with the CRC stages. Conclusion. Our data indicated that CD44 and OCT3/4 may play a role in CRC progression.
References
Morgan E, Arnold M, Gini A. Global burden of colorectal cancer in 2020 and 2040: incidence and mortality esti- mates from GLOBOCAN. Gut. 2023;72:338-344. https://doi.org/10.1136/gutjnl-2022-327736
Ibrahem S, Ahmed H, Zangana S. Trends in colorectal cancer in Iraq over two decades: incidence, mortality, topog- raphy and morphology. Ann Saudi Med. 2022;42(4):252-261. https://doi.org/10.5144/0256-4947.2022.252
Alrubaiy L, AL-Rubaye A, Alrudainy W. Colonoscopy colorectal cancer screening program in southern Iraq: chal- lenges, knowledge gaps and future potential. J Pers Med. 2023;19(2):173. https://doi.org/10.3390/jpm13020173
Kalantari E, Taheri T, Fata S, et al. Significant co-expression of putative cancer stem cell markers, EpCAm and CD166, correlates with tumor stage and invasive behavior in colorectal cancer. World J Surg Onc. 2022;20:15. https://doi.org/10.1186/s12957-021-02469-y
Fedyanin M, Popova A, Polyanskaya E, Tjulandin S. Role of stem cells in colorectal cancer characteristics of stem cell markers in colorectal cancer. Curr Stem Cell Res Ther. 2017;12(1):19-30. https://doi.org/10.2174/1574 888x11666160905092938
Nagano O, Murakami D, Hartmann D. Cell matrix interaction via CD44 is independently regulated by different metalloproteinase’s activated in response to extracellular Ca (2+) influx and PKC activation. J Cell Biol. 2004;165: 893-902. https://doi.org/10.1083/jcb.200310024
Naor D, Nedvetzki S, Golan I, et al. CD44 in cancer. Crit Rev Clin Lab Sci. 2002;39(6):527-579. https://doi. org/10.1080/10408360290795574
Baek K-H, Choi J, Pei C-Z. Cellular functions of OCT-3/4 regulated by ubiquitination in proliferating cells. Cancers. 2020;12(3):663. https://doi.org/10.3390/cancers12030663
Matin MM, Walsh JR, Gokhale PJ, et al. Specific knockdown of Oct4 and beta2-microglobulin expression by RNA interference in human embryonic stem cells and embryonic carcinoma cells. Stem Cells. 2004;22:659-668. https:// doi.org/10.1634/stemcells.22-5-659
Rao GH, Liu HM, Li BW, et al. Establishment of a human colorectal cancer cell line P6C with stem cell pro- perties and resistance to chemotherapeutic drugs. Acta Pharmacol Sin. 2013;34:793-804. https://doi.org/10.1038/ aps.2013.56
Chaitra LP, Prashant A, Gowthami CS, et al. Detection of cancer stem cell-related markers in different stages of colorectal carcinoma patients of Indian origin by immunohistochemistry. J Cancer Res Ther. 2019;15:75-81. https:// doi.org/10.4103/jcrt.JCRT_991_16
Ziranu P, Aimola V, Pretta A, et al. New horizons in metastatic colorectal cancer: prognostic role of CD44 expres- sion. Cancers. 2023;15:1212. https://doi.org/10.3390/cancers15041212
Wang YD, Cai N, Wu XL, et al. OCT4 promotes tumorigenesis and inhibits apoptosis of cervical cancer cells by mir-125b/bak1 pathway. Cell Death Dis. 2013;4(8):760e. https://doi.org/10.1038/cddis.2013.272
Pierpont TM, Lyndaker AM, Anderson CM, et al. Chemotherapy-induced depletion of oct4-positive cancer stem cells in a mouse model of malignant testicular cancer. Cell Rep. 2017;21:1896-1909. https:// doi.org/10.1016/j.cel- rep.2017.10.078
Pardo M, Lang B, Yu L, et al. An expanded OCT3/4 interaction network: implications for stem cell biology, deve- lopment, and disease. Cell Stem Cell. 2010;6:382-395. https://doi.org/10.1016/j.stem.2010.03.004
Gong P, Boman B, Palazzo J. Study of the expression of ALDH1 and CD44 stem cell markers in male breast can- cers. Open J Pathol. 2013;3(4):174-179. https://doi.org/10.4236/ojpathology.2013.34032
Gires O. Lessons from common markers of tumor-initiating cells in solid cancers. Cell Mol Life Sci. 2011;68(24):4009- 4022. https://doi.org/10.1007/s00018-011-0772-9
Du L, Wang H, He L, et al. CD44 is of functional importance for colorectal cancer stem cells. Clin Cancer Res.
;14(21):6751-6760. https://doi.org/10.1158/1078-0432.CCR-08-1034
Baumann M, Krause M. CD44: a cancer stem cell-related biomarker with predictive potential for radiotherapy.
Clin Cancer Res. 2010;16:5091-5093. https://doi.org/10.1158/1078-0432.CCR-10-2244
Wang C, Xie J, Guo J, et al. Evaluation of CD44 and CD133 as cancer stem cell markers for colorectal cancer. Oncol Rep. 2012;28(4):1301-1308. https://doi.org/10.3892/or.2012.1951.
Dalerba P, Dylla SJ, Park IK, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA. 2007;104(24):10158-10163. https://doi.org/10.1073/pnas.0703478104
Ziranu P, Pretta A, Aimola V, et al. CD44: A new prognostic marker in colorectal cancer? Cancers (Basel). 2024;16(8):1569. doi: 10.3390/cancers16081569
Hu J, Li J, Yue X, et al. Expression of the cancer stem cell markers ABCG2 and OCT-4 in right-sided colon cancer predicts recurrence and poor outcomes. Oncotarget. 2017;8(17):28463-28470. https://doi.org/10.18632/oncotar- get.15307
Choi D, Lee HW, Hur KY, et al. Cancer stem cell markers CD133 and CD24 correlate with invasiveness and dif- ferentiation in colorectal adenocarcinoma. World J Gastroenterol. 2009;15(18):2258-2264. https://doi.org/10.3748/ wjg.15.2258
Zhou H, Tan L, Liu B, Guan XY. Cancer stem cells: Recent insights and therapies. Biochem Pharmacol. 2023; 209:115441. https://doi.org/10.1016/j.bcp.2023.115441
Shibata M, Hoque MO. Targeting cancer stem cells: a strategy for effective eradication of cancer. Cancers. 2019;11(5):732. https://doi.org/10.3390/cancers11050732
Abdou Hassan W, Muqresh M, Omer M. The potential role of CD44 and CD133 in colorectal stem cell cancer. Cureus. 2022;14(10):e30509. https://doi.org/10.7759/cureus.30509
Singh D, Khan MA, Siddique HR. Specific targeting of cancer stem cells by immunotherapy: A possible strata- gem to restrain cancer recurrence and metastasis. Biochem Pharmacol. 2022;198:114955. https://doi.org/10.1016/ j.bcp.2022.114955
Busuioc C, Birla RD, Ultimescu F, et al. Aberrant immunohistochemically expression of OCT3/4 and EMT related markers, Vimentin and E-cadherin, is correlated with adverse histopathological features in colorectal adenocarci- noma. Chirurgia. 2022;117(5):544-555. https://doi.org/10.21614/chirurgia.2782
You L, Guo X, Huang Y. Correlation of cancer stem-cell markers OCT4, SOX2, and NANOG with clinicopatho- logical features and prognosis in operative patients with rectal cancer. Yonsei Med J. 2018;59:35-42. https://doi. org/10.3349/ymj.2018.59.1.35
Aguilar-Gallardo C, Simón C. Cells stem cells, and cancer stem cells. Semin Reprod Med. 2013;31:005-013. https:// doi.org/10.1055/s-0032-1331792
Zhang J, Espinoza LA, Kinders RJ, et al. NANOG modulates stemness in human colorectal cancer. Oncogene. 2013;32(37):4397-4405. https://doi.org/10.1038/onc.2012.461
Gazouli M, Roubelakis MG, Theodoropoulos GE, et al. OCT4 spliced variant OCT4B1 is expressed in human colorectal cancer. Mol Carcinog. 2012;51(2):165-173. https://doi.org/10.1002/mc.20773
Vijayakumar G, Narwal A, Kamboj M, Sen R. Association of SOX2, OCT4 and WNT5A expression in oral epi- thelial dysplasia and oral squamous cell carcinoma: an immunohistochemical study. Head Neck Pathol. 2020;4:1-9. https://doi.org/10.1007/s12105-019-01114-1
Tiwari D, Ray Das C, Sultana R, et al. Impact of modulation of telomerase and cancer stem-cell marker OCT4 axis in cervical cancer pathogenesis with underlying HPV16 infection. J Cell Biochem. 2020;121(4):2782-2791. https:// doi.org/10.1002/jcb.29501
Talebi A, Kianersi K, Beiraghdar M. Comparison of gene expression of SOX2 and OCT4 in normal tissue, po- lyps, and colon adenocarcinoma using immunohistochemical staining. Adv Biomed Res. 2015;4:234. https://doi. org/10.4103/2277-9175.167958
Saigusa S, Tanaka K, Toiyama Y, et al. Correlation of CD133, OCT4, and SOX2 in rectal cancer and their as- sociation with distant recurrence after chemoradiotherapy. Ann Surg Oncol. 2009;16(12):3488-3498. https://doi. org/10.1245/s10434-009-0617-z
Matsuoka J, Yashiro M, Sakurai K, et al. Role of the stemness factors SOX2, OCT3/4, and NANOG in gastric car- cinoma. J Sur Res. 2012;174:130-135. https://doi.org/10.1016/j.jss.2010.11.903
Roudi R, Barodabi M, Madjd Z, et al. Expression patterns and clinical significance of the potential cancer stem cell markers OCT4 and NANOG in colorectal cancer patients. Mol Cell Oncol. 2020;7(5):1788366. https://doi.org/10.1 080/23723556.2020.1788366
Trivanović D, Krstić J, Jauković A, et al. Mesenchymal stromal cell engagement in cancer cell epithelial to mesen- chymal transition. Dev Dyn. 2018;247(3):359-367. https://doi.org/10.1002/dvdy.24583
Dongre A, Weinberg RA. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol. 2019;20(2):69-84. https://doi.org/10.1038/s41580-018-0080-4
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Experimental Oncology

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.