Skip to main content
Erschienen in: Tumor Biology 6/2014

01.06.2014 | Research Article

Clinical significance of the stem cell gene Oct-4 in cervical cancer

verfasst von: Yanyan Yang, Yimin Wang, Chunxia Yin, Xiuying Li

Erschienen in: Tumor Biology | Ausgabe 6/2014

Einloggen, um Zugang zu erhalten

Abstract

This study aims to investigate the association between the expression of Oct-4 and the biological behavior or prognosis of cervical cancer. Serum-free suspension culture technology was used to select a suspension of microspheres that can stabilize clones. The tumorigenicity of the microsphere suspension was analyzed in NOD/SCID mice. Microarray analysis was used to detect the specific expression of genes in the microsphere suspension. The expression of Oct-4 was detected by immunohistochemistry, and the correlation between Oct-4 expression and clinical pathological prognostic indicators was analyzed in cervical cancer. The expression of the following genes was significantly different between the experimental and control groups: stem cell differentiation (CD44 and Oct-4), markers cell cycle regulators (APC), cell cycle regulators (MYC), and self-renewal markers (MYST2, NEUROG2, and SOX1). The expression of Oct-4 was significantly higher in cervical cancer tissues than in adjacent normal tissues and was significantly related to differentiation, clinical stage, and lymph node metastasis. The 5-year survival rate of patients with Oct-4-positive expression was lower than that of patients with Oct-4-negative expression (36.7 vs. 67.7 %, respectively; P = 0.001). Cox regression analysis revealed that clinical stage, lymph node metastasis, and Oct-4 were independent prognostic factors in cervical cancer (P = 0.031, 0.012, and 0.001, respectively). Our results showed that Oct-4 was highly expressed in cervical cancer stem cells; Oct-4 expression was associated with biological behavior and was an independent prognostic factor in cervical cancer. Therefore, it may represent a potential target for cervical cancer treatment.
Literatur
1.
Zurück zum Zitat Massad LS. New guidelines on cervical cancer screening: more than just the end of annual pap testing. J Low Genit Tract Dis. 2012;16(3):172–4.CrossRefPubMed Massad LS. New guidelines on cervical cancer screening: more than just the end of annual pap testing. J Low Genit Tract Dis. 2012;16(3):172–4.CrossRefPubMed
2.
Zurück zum Zitat Rao QX, Yao TT, Zhang BZ, Lin RC, Chen ZL, Zhou H, et al. Expression and functional role of ALDH1 in cervical carcinoma cells. Asian Pac J Cancer Prev. 2012;13(4):1325–31.CrossRefPubMed Rao QX, Yao TT, Zhang BZ, Lin RC, Chen ZL, Zhou H, et al. Expression and functional role of ALDH1 in cervical carcinoma cells. Asian Pac J Cancer Prev. 2012;13(4):1325–31.CrossRefPubMed
3.
Zurück zum Zitat Gu TT, Liu SY, Zheng PS. Cytoplasmic NANOG-positive stromal cells promote human cervical cancer progression. Am J Pathol. 2012;181(2):652–61.CrossRefPubMed Gu TT, Liu SY, Zheng PS. Cytoplasmic NANOG-positive stromal cells promote human cervical cancer progression. Am J Pathol. 2012;181(2):652–61.CrossRefPubMed
4.
Zurück zum Zitat Liu R, Wang X, Chen GY, Dalerba P, Gurney A, Hoey T, et al. The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med. 2007;356(3):217–26.CrossRefPubMed Liu R, Wang X, Chen GY, Dalerba P, Gurney A, Hoey T, et al. The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med. 2007;356(3):217–26.CrossRefPubMed
6.
Zurück zum Zitat Sullivan JP, Minna JD, Shay JW. Evidence for self-renewing lung cancer stem cells and their implications in tumor initiation, progression, and targeted therapy. Cancer Metastasis Rev. 2010;29(1):61–72.PubMedCentralCrossRefPubMed Sullivan JP, Minna JD, Shay JW. Evidence for self-renewing lung cancer stem cells and their implications in tumor initiation, progression, and targeted therapy. Cancer Metastasis Rev. 2010;29(1):61–72.PubMedCentralCrossRefPubMed
7.
Zurück zum Zitat Monsef N, Soller M, Isaksson M, Abrahamsson PA, Panagopoulos I. The expression of pluripotency marker Oct 3/4 in prostate cancer and benign prostate hyperplasia. Prostate. 2009;69(9):909–16.CrossRefPubMed Monsef N, Soller M, Isaksson M, Abrahamsson PA, Panagopoulos I. The expression of pluripotency marker Oct 3/4 in prostate cancer and benign prostate hyperplasia. Prostate. 2009;69(9):909–16.CrossRefPubMed
8.
Zurück zum Zitat Liu T, Huang Y, Huang Q, Jiang L, Guo L, Liu Z. Use of human amniotic epithelial cells as a feeder layer to support undifferentiated growth of mouse spermatogonial stem cells via epigenetic regulation of the Nanog and Oct-4 promoters. Acta Biol Hung. 2012;63(2):167–79.CrossRefPubMed Liu T, Huang Y, Huang Q, Jiang L, Guo L, Liu Z. Use of human amniotic epithelial cells as a feeder layer to support undifferentiated growth of mouse spermatogonial stem cells via epigenetic regulation of the Nanog and Oct-4 promoters. Acta Biol Hung. 2012;63(2):167–79.CrossRefPubMed
9.
Zurück zum Zitat van de Geijn GJ, Hersmus R, Looijenga LH. Recent developments in testicular germ cell tumor research. Birth Defects Res C Embryo Today. 2009;87(1):96–113.CrossRefPubMed van de Geijn GJ, Hersmus R, Looijenga LH. Recent developments in testicular germ cell tumor research. Birth Defects Res C Embryo Today. 2009;87(1):96–113.CrossRefPubMed
10.
Zurück zum Zitat Liu CG, Lu Y, Wang BB, Zhang YJ, Zhang RS, Lu Y, et al. Clinical implications of stem cell gene Oct-4 expression in breast cancer. Ann Surg. 2011;253(6):1165–71.CrossRefPubMed Liu CG, Lu Y, Wang BB, Zhang YJ, Zhang RS, Lu Y, et al. Clinical implications of stem cell gene Oct-4 expression in breast cancer. Ann Surg. 2011;253(6):1165–71.CrossRefPubMed
11.
Zurück zum Zitat Zhang SL, Wang YS, Zhou T, Yu XW, Wei ZT, Li YL. Isolation and characterization of cancer stem cells from cervical cancer HeLa cells. Cytotechnology. 2012;64(4):477–84.PubMedCentralCrossRefPubMed Zhang SL, Wang YS, Zhou T, Yu XW, Wei ZT, Li YL. Isolation and characterization of cancer stem cells from cervical cancer HeLa cells. Cytotechnology. 2012;64(4):477–84.PubMedCentralCrossRefPubMed
12.
Zurück zum Zitat Trosko JE. From adult stem cells to cancer stem cells: Oct-4 gene, cell-cell communication, and hormones during tumor promotion. Ann N Y Acad Sci. 2006;1089:36–58.CrossRefPubMed Trosko JE. From adult stem cells to cancer stem cells: Oct-4 gene, cell-cell communication, and hormones during tumor promotion. Ann N Y Acad Sci. 2006;1089:36–58.CrossRefPubMed
13.
Zurück zum Zitat Cai J, Xie D, Fan Z, Chipperfield H, Marden J, Wong WH, et al. Modeling co-expression across species for complex traits: insights to the difference of human and mouse embryonic stem cells. PLoS Comput Biol. 2010;6(3):e1000707.PubMedCentralCrossRefPubMed Cai J, Xie D, Fan Z, Chipperfield H, Marden J, Wong WH, et al. Modeling co-expression across species for complex traits: insights to the difference of human and mouse embryonic stem cells. PLoS Comput Biol. 2010;6(3):e1000707.PubMedCentralCrossRefPubMed
14.
Zurück zum Zitat Wen J, Park JY, Park KH, Chung HW, Bang S, Park SW, et al. Oct4 and Nanog expression is associated with early stages of pancreatic carcinogenesis. Pancreas. 2010;39(5):622–6.CrossRefPubMed Wen J, Park JY, Park KH, Chung HW, Bang S, Park SW, et al. Oct4 and Nanog expression is associated with early stages of pancreatic carcinogenesis. Pancreas. 2010;39(5):622–6.CrossRefPubMed
15.
Zurück zum Zitat Heng JC, Feng B, Han J, Jiang J, Kraus P, Ng JH, et al. The nuclear receptor Nr5a2 can replace Oct4 in the reprogramming of murine somatic cells to pluripotent cells. Cell Stem Cell. 2010;6(2):167–74.CrossRefPubMed Heng JC, Feng B, Han J, Jiang J, Kraus P, Ng JH, et al. The nuclear receptor Nr5a2 can replace Oct4 in the reprogramming of murine somatic cells to pluripotent cells. Cell Stem Cell. 2010;6(2):167–74.CrossRefPubMed
16.
Zurück zum Zitat Riekstina U, Cakstina I, Parfejevs V, Hoogduijn M, Jankovskis G, Muiznieks I, et al. Embryonic stem cell marker expression pattern in human mesenchymal stem cells derived from bone marrow, adipose tissue, heart and dermis. Stem Cell Rev. 2009;5(4):378–86.CrossRefPubMed Riekstina U, Cakstina I, Parfejevs V, Hoogduijn M, Jankovskis G, Muiznieks I, et al. Embryonic stem cell marker expression pattern in human mesenchymal stem cells derived from bone marrow, adipose tissue, heart and dermis. Stem Cell Rev. 2009;5(4):378–86.CrossRefPubMed
17.
Zurück zum Zitat Cantz T, Key G, Bleidissel M, Gentile L, Han DW, Brenne A, et al. Absence of OCT4 expression in somatic tumor cell lines. Stem Cells. 2008;26(3):692–7.CrossRefPubMed Cantz T, Key G, Bleidissel M, Gentile L, Han DW, Brenne A, et al. Absence of OCT4 expression in somatic tumor cell lines. Stem Cells. 2008;26(3):692–7.CrossRefPubMed
18.
Zurück zum Zitat Tai MH, Chang CC, Kiupel M, Webster JD, Olson LK, Trosko JE. Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis. 2005;26(2):495–502.CrossRefPubMed Tai MH, Chang CC, Kiupel M, Webster JD, Olson LK, Trosko JE. Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis. 2005;26(2):495–502.CrossRefPubMed
19.
Zurück zum Zitat Feng D, Peng C, Li C, Zhou Y, Li M, Ling B, et al. Identification and characterization of cancer stem-like cells from primary carcinoma of the cervix uteri. Oncol Rep. 2009;22(5):1129–34.PubMed Feng D, Peng C, Li C, Zhou Y, Li M, Ling B, et al. Identification and characterization of cancer stem-like cells from primary carcinoma of the cervix uteri. Oncol Rep. 2009;22(5):1129–34.PubMed
20.
Zurück zum Zitat Wang YD, Cai N, Wu XL, Cao HZ, Xie LL, Zheng PS. OCT4 promotes tumorigenesis and inhibits apoptosis of cervical cancer cells by miR-125b/BAK1 pathway. Cell Death Dis. 2013;4:e760.PubMedCentralCrossRefPubMed Wang YD, Cai N, Wu XL, Cao HZ, Xie LL, Zheng PS. OCT4 promotes tumorigenesis and inhibits apoptosis of cervical cancer cells by miR-125b/BAK1 pathway. Cell Death Dis. 2013;4:e760.PubMedCentralCrossRefPubMed
Metadaten
Titel
Clinical significance of the stem cell gene Oct-4 in cervical cancer
verfasst von
Yanyan Yang
Yimin Wang
Chunxia Yin
Xiuying Li
Publikationsdatum
01.06.2014
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 6/2014
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-1696-4

Weitere Artikel der Ausgabe 6/2014

Tumor Biology 6/2014 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

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