Skip to main content
Erschienen in: Journal of Gastrointestinal Cancer 1/2020

09.01.2019 | Original Research

Association of High Expression Levels of SOX2, NANOG, and OCT4 in Gastric Cancer Tumor Tissues with Progression and Poor Prognosis

verfasst von: Gholam Basati, Hadiseh Mohammadpour, Amirnader Emami Razavi

Erschienen in: Journal of Gastrointestinal Cancer | Ausgabe 1/2020

Einloggen, um Zugang zu erhalten

Abstract

Background

Expression of the essential regulator genes, SOX2, NANOG, and OCT4, so-called as stemness factors, is prerequisite for the tumorigenic capability of cancer stem cells (CSCs) and their potential role in the formation and progression of various human cancers.

Methods

In this study, the expression levels of SOX2, NANOG, and OCT4 were quantified by a qRT-PCR method in 100 gastric cancer tumor tissues vs the paired adjacent normal tissues. Then, the relationship between the expression of the three genes in gastric cancer tumor tissues and the clinicopathological characteristics and overall survival of patients was investigated.

Results

Higher expression levels of SOX2, NANOG, and OCT4 were found in gastric cancer tumor tissues compared with those in paired adjacent normal tissues (P = 0.0001). Overexpression of the mentioned genes in gastric cancer tumor tissues was resolved to be significantly associated with tumor size (P < 0.05), TNM stage (P = 0.001), tumor grade (P < 0.01), and shortened overall survival time (P = 0.0001).

Conclusions

These findings indicted that the stemness factors SOX2, NANOG, and OCT4 are significantly overexpressed in gastric cancer and may serve as potential biomarkers of gastric cancer progression and prognosis.
Literatur
1.
Zurück zum Zitat Chang JC. Cancer stem cells: role in tumor growth, recurrence, metastasis, and treatment resistance. Medicine (Baltimore). 2016 Sep;95(1 Suppl 1):S20–5.CrossRef Chang JC. Cancer stem cells: role in tumor growth, recurrence, metastasis, and treatment resistance. Medicine (Baltimore). 2016 Sep;95(1 Suppl 1):S20–5.CrossRef
3.
Zurück zum Zitat Moharil R, Dive A, Khandekar S, Bodhade A. Cancer stem cells: an insight. J Oral Maxillofac Pathol. 2017 Sep-Dec;21(3):463.CrossRef Moharil R, Dive A, Khandekar S, Bodhade A. Cancer stem cells: an insight. J Oral Maxillofac Pathol. 2017 Sep-Dec;21(3):463.CrossRef
4.
Zurück zum Zitat Bu Y, Cao D. The origin of cancer stem cells. Front Biosci (Schol Ed). 2012;4:819–30. Bu Y, Cao D. The origin of cancer stem cells. Front Biosci (Schol Ed). 2012;4:819–30.
8.
Zurück zum Zitat Ohnishi K, Semi K, Yamamoto T, Shimizu M, Tanaka A, Mitsunaga K, et al. Premature termination of reprogramming in vivo leads to cancer development through altered epigenetic regulation. Cell. 2014;156(4):663–77.CrossRef Ohnishi K, Semi K, Yamamoto T, Shimizu M, Tanaka A, Mitsunaga K, et al. Premature termination of reprogramming in vivo leads to cancer development through altered epigenetic regulation. Cell. 2014;156(4):663–77.CrossRef
9.
Zurück zum Zitat Zhao W, Li Y, Zhang X. Stemness-related markers in cancer. Cancer Transl Med. 2017;3(3):87–95.CrossRef Zhao W, Li Y, Zhang X. Stemness-related markers in cancer. Cancer Transl Med. 2017;3(3):87–95.CrossRef
10.
Zurück zum Zitat Zhang X, Yu H, Yang Y, Zhu R, Bai J, Peng Z, et al. SOX2 in gastric carcinoma, but not Hath1, is related to patients’ clinicopathological features and prognosis. J Gastrointest Surg. 2010;14(8):1220–6.CrossRef Zhang X, Yu H, Yang Y, Zhu R, Bai J, Peng Z, et al. SOX2 in gastric carcinoma, but not Hath1, is related to patients’ clinicopathological features and prognosis. J Gastrointest Surg. 2010;14(8):1220–6.CrossRef
11.
Zurück zum Zitat Chen Z, Xu WR, Qian H, Zhu W, Bu XF, Wang S, et al. Oct4, a novel marker for human gastric cancer. J Surg Oncol. 2009;99(7):414–9.CrossRef Chen Z, Xu WR, Qian H, Zhu W, Bu XF, Wang S, et al. Oct4, a novel marker for human gastric cancer. J Surg Oncol. 2009;99(7):414–9.CrossRef
12.
Zurück zum Zitat Matsuoka J, Yashiro M, Sakurai K, Kubo N, Tanaka H, Muguruma K, et al. Role of the stemness factors sox2, oct3/4, and nanog in gastric carcinoma. J Surg Res. 2012;174(1):130–5.CrossRef Matsuoka J, Yashiro M, Sakurai K, Kubo N, Tanaka H, Muguruma K, et al. Role of the stemness factors sox2, oct3/4, and nanog in gastric carcinoma. J Surg Res. 2012;174(1):130–5.CrossRef
13.
Zurück zum Zitat Li N, Deng W, Ma J, Wei B, Guo K, Shen W, et al. Prognostic evaluation of Nanog, Oct4, Sox2, PCNA, Ki67 and E-cadherin expression in gastric cancer. Med Oncol. 2015;32(1):433.CrossRef Li N, Deng W, Ma J, Wei B, Guo K, Shen W, et al. Prognostic evaluation of Nanog, Oct4, Sox2, PCNA, Ki67 and E-cadherin expression in gastric cancer. Med Oncol. 2015;32(1):433.CrossRef
14.
Zurück zum Zitat Asadi MH, Mowla SJ, Fathi F, Aleyasin A, Asadzadeh J, Atlasi Y. OCT4B1, a novel spliced variant of OCT4, is highly expressed in gastric cancer and acts as an antiapoptotic factor. Int J Cancer. 2011;128(11):2645–52.CrossRef Asadi MH, Mowla SJ, Fathi F, Aleyasin A, Asadzadeh J, Atlasi Y. OCT4B1, a novel spliced variant of OCT4, is highly expressed in gastric cancer and acts as an antiapoptotic factor. Int J Cancer. 2011;128(11):2645–52.CrossRef
15.
Zurück zum Zitat Wuebben E, Oncotarget AR. The dark side of SOX2: cancer-a comprehensive overview. Oncotarget. 2017;8(27):44917–43.CrossRef Wuebben E, Oncotarget AR. The dark side of SOX2: cancer-a comprehensive overview. Oncotarget. 2017;8(27):44917–43.CrossRef
16.
Zurück zum Zitat Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 2001;25(4):402–8.CrossRef Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 2001;25(4):402–8.CrossRef
17.
Zurück zum Zitat Liu A, Yu X, Liu S. Pluripotency transcription factors and cancer stem cells: small genes make a big difference. Chin J Cancer. 2013;32(9):483–7.PubMedPubMedCentral Liu A, Yu X, Liu S. Pluripotency transcription factors and cancer stem cells: small genes make a big difference. Chin J Cancer. 2013;32(9):483–7.PubMedPubMedCentral
18.
Zurück zum Zitat Hadjimichael C, Chanoumidou K, Papadopoulou N, et al. Common stemness regulators of embryonic and cancer stem cells. World J Stem Cells. 2015;7(9):1150–84.PubMedPubMedCentral Hadjimichael C, Chanoumidou K, Papadopoulou N, et al. Common stemness regulators of embryonic and cancer stem cells. World J Stem Cells. 2015;7(9):1150–84.PubMedPubMedCentral
19.
Zurück zum Zitat Luo W, Li S, Peng B, Ye Y, Deng X, Yao K. Embryonic stem cells markers SOX2, OCT4 and Nanog expression and their correlations with epithelial-mesenchymal transition in nasopharyngeal carcinoma. PLoS One. 2013;8(2):e56324.CrossRef Luo W, Li S, Peng B, Ye Y, Deng X, Yao K. Embryonic stem cells markers SOX2, OCT4 and Nanog expression and their correlations with epithelial-mesenchymal transition in nasopharyngeal carcinoma. PLoS One. 2013;8(2):e56324.CrossRef
20.
Zurück zum Zitat Hütz K, Mejías-Luque R, Farsakova K, et al. The stem cell factor SOX2 regulates the tumorigenic potential in human gastric cancer cells. Carcinogenesis. 2013;35(4):942–50.CrossRef Hütz K, Mejías-Luque R, Farsakova K, et al. The stem cell factor SOX2 regulates the tumorigenic potential in human gastric cancer cells. Carcinogenesis. 2013;35(4):942–50.CrossRef
21.
Zurück zum Zitat Tian T, Zhang Y, Wang S, Zhou J, Xu S. Sox2 enhances the tumorigenicity and chemoresistance of cancer stem-like cells derived from gastric cancer. J Biomed Res. 2012;26(5):336–45.CrossRef Tian T, Zhang Y, Wang S, Zhou J, Xu S. Sox2 enhances the tumorigenicity and chemoresistance of cancer stem-like cells derived from gastric cancer. J Biomed Res. 2012;26(5):336–45.CrossRef
22.
Zurück zum Zitat Tian Y, Jia X, Wang S, Li Y, Zhao P, Cai D, et al. SOX2 oncogenes amplified and operate to activate AKT signaling in gastric cancer and predict immunotherapy responsiveness. J Cancer Res Clin Oncol. 2014;140(7):1117–24.CrossRef Tian Y, Jia X, Wang S, Li Y, Zhao P, Cai D, et al. SOX2 oncogenes amplified and operate to activate AKT signaling in gastric cancer and predict immunotherapy responsiveness. J Cancer Res Clin Oncol. 2014;140(7):1117–24.CrossRef
23.
Zurück zum Zitat Li XL, Eishi Y, Bai YQ, Sakai H, Akiyama Y, Tani M, et al. Expression of the SRY-related HMG box protein SOX2 in human gastric carcinoma. Int J Oncol. 2004;24(2):257–63.PubMed Li XL, Eishi Y, Bai YQ, Sakai H, Akiyama Y, Tani M, et al. Expression of the SRY-related HMG box protein SOX2 in human gastric carcinoma. Int J Oncol. 2004;24(2):257–63.PubMed
24.
Zurück zum Zitat Otsubo T, Akiyama Y, Yanagihara K, Yuasa Y. SOX2 is frequently downregulated in gastric cancers and inhibits cell growth through cell-cycle arrest and apoptosis. Br J Cancer. 2008;98(4):824–31.CrossRef Otsubo T, Akiyama Y, Yanagihara K, Yuasa Y. SOX2 is frequently downregulated in gastric cancers and inhibits cell growth through cell-cycle arrest and apoptosis. Br J Cancer. 2008;98(4):824–31.CrossRef
26.
Zurück zum Zitat Wang S, Tie J, Wang R, Hu F, Gao L, Wang W, et al. SOX2, a predictor of survival in gastric cancer, inhibits cell proliferation and metastasis by regulating PTEN. Cancer Lett. 2015;358(2):210–9.CrossRef Wang S, Tie J, Wang R, Hu F, Gao L, Wang W, et al. SOX2, a predictor of survival in gastric cancer, inhibits cell proliferation and metastasis by regulating PTEN. Cancer Lett. 2015;358(2):210–9.CrossRef
27.
Zurück zum Zitat Khalili M, Vasei M, Khalili D, Alimoghaddam K, Sadeghizadeh M, Mowla SJ. Downregulation of the genes involved in reprogramming (SOX2, c-MYC, miR-302, miR-145, and P21) in gastric adenocarcinoma. J Gastrointest Cancer. 2015;46(3):251–8.CrossRef Khalili M, Vasei M, Khalili D, Alimoghaddam K, Sadeghizadeh M, Mowla SJ. Downregulation of the genes involved in reprogramming (SOX2, c-MYC, miR-302, miR-145, and P21) in gastric adenocarcinoma. J Gastrointest Cancer. 2015;46(3):251–8.CrossRef
28.
Zurück zum Zitat Shen W, Xie J, Zhao S, du R, Luo X, He H, et al. ICAM3 mediates inflammatory signaling to promote cancer cell stemness. Cancer Lett. 2018;422:29–43.CrossRef Shen W, Xie J, Zhao S, du R, Luo X, He H, et al. ICAM3 mediates inflammatory signaling to promote cancer cell stemness. Cancer Lett. 2018;422:29–43.CrossRef
29.
Zurück zum Zitat Long W, Zhao W, Ning B, et al. PHF20 collaborates with PARP1 to promote stemness and aggressiveness of neuroblastoma cells through activation of SOX2 and OCT4. J Mol Cell Biol. 2018;14. Long W, Zhao W, Ning B, et al. PHF20 collaborates with PARP1 to promote stemness and aggressiveness of neuroblastoma cells through activation of SOX2 and OCT4. J Mol Cell Biol. 2018;14.
30.
Zurück zum Zitat You L, Guo X, Huang Y. Correlation of cancer stem-cell markers OCT4, SOX2, and NANOG with clinicopathological features and prognosis in operative patients with rectal. Yonsei Med J. 2018;59(1):35–42.CrossRef You L, Guo X, Huang Y. Correlation of cancer stem-cell markers OCT4, SOX2, and NANOG with clinicopathological features and prognosis in operative patients with rectal. Yonsei Med J. 2018;59(1):35–42.CrossRef
31.
Zurück zum Zitat Jiang W, Zhang P, Li G, Dong JH, Wang XS, Wang YY. Oct-4 is associated with gastric cancer progression and prognosis. Onco Targets Ther. 2016;9:517–22.PubMedPubMedCentral Jiang W, Zhang P, Li G, Dong JH, Wang XS, Wang YY. Oct-4 is associated with gastric cancer progression and prognosis. Onco Targets Ther. 2016;9:517–22.PubMedPubMedCentral
32.
Zurück zum Zitat Li N, Wang W, Xu B, Gong H. OCT3/4 expression is correlated with the invasion of gastric carcinoma. Oncol Lett. 2014;8(1):12–6.CrossRef Li N, Wang W, Xu B, Gong H. OCT3/4 expression is correlated with the invasion of gastric carcinoma. Oncol Lett. 2014;8(1):12–6.CrossRef
33.
Zurück zum Zitat Yong X, Tang B, Xiao Y, et al. Helicobacter pylori upregulates Nanog and Oct4 via Wnt/β-catenin signaling pathway to promote cancer stem cell-like properties in human gastric cancer. Cancer Lett. 2016;374(2):292–303.CrossRef Yong X, Tang B, Xiao Y, et al. Helicobacter pylori upregulates Nanog and Oct4 via Wnt/β-catenin signaling pathway to promote cancer stem cell-like properties in human gastric cancer. Cancer Lett. 2016;374(2):292–303.CrossRef
34.
Zurück zum Zitat Iv Santaliz-Ruiz LE, Xie X, Old M, et al. Emerging role of nanog in tumorigenesis and cancer stem cells. Int J Cancer. 2014;135(12):2741–8.CrossRef Iv Santaliz-Ruiz LE, Xie X, Old M, et al. Emerging role of nanog in tumorigenesis and cancer stem cells. Int J Cancer. 2014;135(12):2741–8.CrossRef
35.
Zurück zum Zitat Zhang J, Wang X, Chen B, et al. The human pluripotency gene NANOG/NANOGP8 is expressed in gastric cancer and associated with tumor development. Oncol Lett. 2010;1(3):457–63.CrossRef Zhang J, Wang X, Chen B, et al. The human pluripotency gene NANOG/NANOGP8 is expressed in gastric cancer and associated with tumor development. Oncol Lett. 2010;1(3):457–63.CrossRef
36.
Zurück zum Zitat Lin T, Ding YQ, Li JM. Overexpression of Nanog protein is associated with poor prognosis in gastric adenocarcinoma. Med Oncol. 2012;29(2):878–85.CrossRef Lin T, Ding YQ, Li JM. Overexpression of Nanog protein is associated with poor prognosis in gastric adenocarcinoma. Med Oncol. 2012;29(2):878–85.CrossRef
Metadaten
Titel
Association of High Expression Levels of SOX2, NANOG, and OCT4 in Gastric Cancer Tumor Tissues with Progression and Poor Prognosis
verfasst von
Gholam Basati
Hadiseh Mohammadpour
Amirnader Emami Razavi
Publikationsdatum
09.01.2019
Verlag
Springer US
Erschienen in
Journal of Gastrointestinal Cancer / Ausgabe 1/2020
Print ISSN: 1941-6628
Elektronische ISSN: 1941-6636
DOI
https://doi.org/10.1007/s12029-018-00200-x

Weitere Artikel der Ausgabe 1/2020

Journal of Gastrointestinal Cancer 1/2020 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.