Comparison of gene expression of SOX2 and OCT4 in normal tissue, polyps, and colon adenocarcinoma using immunohistochemical staining

Talebi, Ardeshir; Kianersi, Kianoosh; Beiraghdar, Mozhdeh

Comparison of gene expression of SOX2 and OCT4 in normal tissue, polyps, and colon adenocarcinoma using immunohistochemical staining

Authors

Department of Pathology, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Cancer stem cells have been isolated and characterized in all common cancers. SOX2 and OCT4 are important genes to enhance the self-renewal ability as activate stem cells and inhibit the genes that start differentiation and thus maintain the self-renewal ability of stem cells. Also, the aim of this study is "Comparison of gene expression of SOX2 and OCT4 in normal tissue, polyps, and colon adenocarcinoma using immunohistochemical staining."
Materials and Methods: This cross-sectional study conducted on 20 patients so that for each patient, a sample of healthy tissue, dysplastic polyp tissue, and colon adenocarcinoma were provided as microscopic sections and staining on each tissue was performed through immunohistochemistry method by markers OCT4 and SOX2. The collected data were interred into SPSS version 18.0, (SPSS Inc., Chicago, IL, USA) software and the level of significance were considered as <0.05.
Results: The study sample consisted of 20 patients including 11 men (55%) and 9 women (45%) with a mean age of 55.6 ± 9.88 years. There was no association between Oct4 and colorectal cancer (CRC) patients (P > 0.05), but there was a significant correlation between Sox2 expression and CRC (P < 0.05). Patients in many aspects such as race, type of polyp, presence of lymph node, grade and intensity of Sox2 in different types of patients' tissues (P < 0.05).
Conclusion: Regarding our findings, the expression of Sox2 would be a liable marker for evaluating of cancer progression and could be a treatment target of CRC cells.

Keywords

References

1.	Leong AF, Seow-Choen F, Tang CL. Diminutive cancers of the colon and rectum: Comparison between flat and polypoid cancers. Int J Colorectal Dis 1998;13:151-3.
2.	Gostjeva EV, Thilly WG. Stem cell stages and the origins of colon cancer: A multidisciplinary perspective. Stem Cell Rev 2005;1:243-51.
3.	Clarke MF, Fuller M. Stem cells and cancer: Two faces of eve. Cell 2006;124:1111-5.
4.	Avery S, Inniss K, Moore H. The regulation of self-renewal in human embryonic stem cells. Stem Cells Dev 2006;15:729-40.
5.	Rodda DJ, Chew JL, Lim LH, Loh YH, Wang B, Ng HH, et al. Transcriptional regulation of nanog by OCT4 and SOX2. J Biol Chem 2005;280:24731-7.
6.	Padín-Iruegas ME, Herranz-Carnero M, Aguin-Losada S, Brozos-Vazquez E, Anido-Herranz U, Antunez-Lopez JR, et al. Prognostic value of changes in the expression of stem cell markers in the peripheral blood of patients with colon cancer. Oncol Rep 2013;29:2467-72.
7.	Saigusa S, Tanaka K, Toiyama Y, Yokoe T, Okugawa Y, Ioue Y, et al. Correlation of CD133, OCT4, and SOX2 in rectal cancer and their association with distant recurrence after chemoradiotherapy. Ann Surg Oncol 2009;16:3488-98.
8.	Saigusa S, Tanaka K, Toiyama Y, Yokoe T, Okugawa Y, Ioue Y, et al. Correlation of CD133, OCT4, SOX2 in rectal cancer and their association with distant recurrence after chemoradiotherapy. Ann Surg Oncol 2009;16:3488-3498.
9.	Amini S, Fathi F, Parivar K, Mohseni H. Evaluating the Expression of OCT-4, Nanog, SOX2 and Nucleostemin in Colon Cancer Cell Lines (CaCO-2 and HT-29). Cell J 2010;12:223-230.
10.	Neumann J, Bahr F, Horst D, Kriegl L, Engel J, Luque RM, et al. SOX2 expression correlates with lymph-node metastases and distant spread in right-sided colon cancer. BMC Cancer 2011;11:518.
11.	Liu RL, Zhang ZH, Zhao WM, Wang M, Qi SY, Li J, et al. Expression of nucleostemin in prostate cancer and its effect on the proliferation of PC-3 cells. Chin Med J (Engl) 2008;121:299-304.
12.	Capocaccia R, Gatta G, Dal Maso L. Life expectancy of colon, breast, and testicular cancer patients: An analysis of US-SEER population-based data. Ann Oncol 2015;26:1263-8.
13.	Kheirelseid EA, Miller N, Chang KH, Curran C, Hennessey E, Sheehan M, et al. Mismatch repair protein expression in colorectal cancer. J Gastrointest Oncol 2013;4:397-408.
14.	Voutsadakis IA. Pluripotency transcription factors in the pathogenesis of colorectal cancer and implications for prognosis. Biomark Med 2015;9:349-61. [PUBMED]
15.	Bourguignon LY, Wong G, Earle C, Chen L. Hyaluronan-CD44v3 interaction with Oct4-Sox2-Nanog promotes miR-302 expression leading to self-renewal, clonal formation, and cisplatin resistance in cancer stem cells from head and neck squamous cell carcinoma. J Biol Chem 2012;287:32800-24.
16.	Hochedlinger K, Yamada Y, Beard C, Jaenisch R. Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell 2005;121:465-77.
17.	Dai X, Ge J, Wang X, Qian X, Zhang C, Li X. OCT4 regulates epithelial-mesenchymal transition and its knockdown inhibits colorectal cancer cell migration and invasion. Oncol Rep 2013;29:155-60.
18.	Jachin S, Bae JS, Sung JJ, Park HS, Jang KY, Chung MJ, et al. The role of nuclear EpICD in extrahepatic cholangiocarcinoma: Association with ß-catenin. Int J Oncol 2014;45:691-8.
19.	Huang HP, Chen PH, Yu CY, Chuang CY, Stone L, Hsiao WC, et al. Epithelial cell adhesion molecule (EpCAM) complex proteins promote transcription factor-mediated pluripotency reprogramming. J Biol Chem 2011;286:33520-32.
20.	Hao HX, Xie Y, Zhang Y, Charlat O, Oster E, Avello M, et al. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature 2012;485:195-200.
21.	Amini S, Fathi F, Mobalegi J, Sofimajidpour H, Ghadimi T. The expressions of stem cell markers: Oct4, Nanog, Sox2, nucleostemin, Bmi, Zfx, Tcl1, Tbx3, Dppa4, and Esrrb in bladder, colon, and prostate cancer, and certain cancer cell lines. Anat Cell Biol 2014;47:1-11.
22.	Papailiou J, Bramis KJ, Gazouli M, Theodoropoulos G. Stem cells in colon cancer. A new era in cancer theory begins. Int J Colorectal Dis 2011;26:1-11.
23.	Sarkar A, Hochedlinger K. The sox family of transcription factors: Versatile regulators of stem and progenitor cell fate. Cell Stem Cell 2013;12:15-30.
24.	Fong YW, Inouye C, Yamaguchi T, Cattoglio C, Grubisic I, Tjian R. A DNA repair complex functions as an Oct4/Sox2 coactivator in embryonic stem cells. Cell 2011;147:120-31.
25.	Jeter CR, Badeaux M, Choy G, Chandra D, Patrawala L, Liu C, et al. Functional evidence that the self-renewal gene NANOG regulates human tumor development. Stem Cells 2009;27:993-1005.
26.	Leis O, Eguiara A, Lopez-Arribillaga E, Alberdi MJ, Hernandez-Garcia S, Elorriaga K, et al. Sox2 expression in breast tumours and activation in breast cancer stem cells. Oncogene 2012;31:1354-65.
27.	Fang X, Yu W, Li L, Shao J, Zhao N, Chen Q, et al. ChIP-seq and functional analysis of the SOX2 gene in colorectal cancers. OMICS 2010;14:369-84.
28.	Pang R, Law WL, Chu AC, Poon JT, Lam CS, Chow AK, et al. A subpopulation of CD26+cancer stem cells with metastatic capacity in human colorectal cancer. Cell Stem Cell 2010;6:603-15.
29.	Sekharam M, Zhao H, Sun M, Fang Q, Zhang Q, Yuan Z, et al. Insulin-like growth factor 1 receptor enhances invasion and induces resistance to apoptosis of colon cancer cells through the Akt/Bcl-x(L) pathway. Cancer Res 2003;63:7708-16.
30.	O'dwyer PJ, Benson AB 3 ^rd . Epidermal growth factor receptor-targeted therapy in colorectal cancer. Semin Oncol 2002;29 5 Suppl 14:10-7.
31.	Kumar V. "17 - Polyps". Robbins and Cotran Pathologic Basis of Disease. 8 ^th ed. Philadelphia, PA: Saunders/Elsevier; 2010.
32.	Neumann J, Bahr F, Horst D, Kriegl L, Engel J, Luque RM, et al. SOX2 expression correlates with lymph-node metastases and distant spread in right-sided colon cancer. BMC Cancer 2011;11:518.
33.	Han X, Fang X, Lou X, Hua D, Ding W, Foltz G, et al. Silencing SOX2 induced mesenchymal-epithelial transition and its expression predicts liver and lymph node metastasis of CRC patients. PLoS One 2012;7:e41335.

Advanced Biomedical Research