Clinical Significance of the Stem Cell Gene Oct-4 in Cervical Cancer

Overview

Journal Tumour Biol

Publisher Sage Publications

Specialty Oncology

Date 2014 Feb 18

PMID 24532469

Citations 16

Authors

Yanyan Yang

Yimin Wang

ChunXia Yin

Xiuying Li

Affiliations

Soon will be listed here.

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.

Citing Articles

Association of CD133, ALDH1, CD117 and OCT4 expression with prognosis of patients with cervical cancer.

Almeida T, Dos Santos O, Saddi V, Pereira J, Machado H, Santos Carneiro M Virchows Arch. 2024; .

PMID: 38981932 DOI: 10.1007/s00428-024-03862-0.

Targeting Cervical Cancer Stem Cells by Phytochemicals.

Tripathi T, Yadav J, Janjua D, Chaudhary A, Joshi U, Senrung A Curr Med Chem. 2024; 31(32):5222-5254.

PMID: 38288813 DOI: 10.2174/0109298673281823231222065616.

ELK4 Promotes Cell Cycle Progression and Stem Cell-like Characteristics in HPV-associated Cervical Cancer by Regulating the FBXO22/PTEN Axis.

Gao F, Wang C, Bai X, Ji J, Huang X Balkan Med J. 2023; 40(6):409-414.

PMID: 37519006 PMC: 10613738. DOI: 10.4274/balkanmedj.galenos.2023.2023-4-66.

Cervical cancer heterogeneity: a constant battle against viruses and drugs.

Sun Q, Wang L, Zhang C, Hong Z, Han Z Biomark Res. 2022; 10(1):85.

PMID: 36397138 PMC: 9670454. DOI: 10.1186/s40364-022-00428-7.

ALDH1 & CD133 in invasive cervical carcinoma & their association with the outcome of chemoradiation therapy.

Javed S, Sood S, Rai B, Bhattacharyya S, Bagga R, Srinivasan R Indian J Med Res. 2022; 154(2):367-374.

PMID: 35295009 PMC: 9131751. DOI: 10.4103/ijmr.IJMR_709_20.

References

Massad L . 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. DOI: 10.1097/LGT.0b013e31824bc178. View

Gu T, Liu S, Zheng P . Cytoplasmic NANOG-positive stromal cells promote human cervical cancer progression. Am J Pathol. 2012; 181(2):652-61. DOI: 10.1016/j.ajpath.2012.04.008. View

Zhang S, Wang Y, Zhou T, Yu X, Wei Z, Li Y . Isolation and characterization of cancer stem cells from cervical cancer HeLa cells. Cytotechnology. 2012; 64(4):477-84. PMC: 3397111. DOI: 10.1007/s10616-012-9436-3. View

Riekstina U, Cakstina I, Parfejevs V, Hoogduijn M, Jankovskis G, Muiznieks I . Embryonic stem cell marker expression pattern in human mesenchymal stem cells derived from bone marrow, adipose tissue, heart and dermis. Stem Cell Rev Rep. 2010; 5(4):378-86. DOI: 10.1007/s12015-009-9094-9. View

Heng J, Feng B, Han J, Jiang J, Kraus P, Ng J . 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. DOI: 10.1016/j.stem.2009.12.009. View

Monsef N, Soller M, Isaksson M, Abrahamsson P, Panagopoulos I . The expression of pluripotency marker Oct 3/4 in prostate cancer and benign prostate hyperplasia. Prostate. 2009; 69(9):909-16. DOI: 10.1002/pros.20934. View

Sullivan J, Minna J, Shay J . 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. PMC: 2864581. DOI: 10.1007/s10555-010-9216-5. View

Liu R, Wang X, Chen G, Dalerba P, Gurney A, Hoey T . The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med. 2007; 356(3):217-26. DOI: 10.1056/NEJMoa063994. View

Cai J, Xie D, Fan Z, Chipperfield H, Marden J, Wong W . 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. PMC: 2837392. DOI: 10.1371/journal.pcbi.1000707. View

10.

Wen J, Park J, Park K, Chung H, Bang S, Park S . Oct4 and Nanog expression is associated with early stages of pancreatic carcinogenesis. Pancreas. 2010; 39(5):622-6. DOI: 10.1097/MPA.0b013e3181c75f5e. View

11.

Liu C, Lu Y, Wang B, Zhang Y, Zhang R, Lu Y . Clinical implications of stem cell gene Oct-4 expression in breast cancer. Ann Surg. 2011; 253(6):1165-71. DOI: 10.1097/SLA.0b013e318214c54e. View

12.

Rao Q, Yao T, Zhang B, Lin R, Chen Z, Zhou H . Expression and functional role of ALDH1 in cervical carcinoma cells. Asian Pac J Cancer Prev. 2012; 13(4):1325-31. DOI: 10.7314/apjcp.2012.13.4.1325. View

13.

Cantz T, Key G, Bleidissel M, Gentile L, Han D, Brenne A . Absence of OCT4 expression in somatic tumor cell lines. Stem Cells. 2007; 26(3):692-7. DOI: 10.1634/stemcells.2007-0657. View

14.

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. DOI: 10.1556/ABiol.63.2012.2.1. View

15.

Merlo L, Maley C . The role of genetic diversity in cancer. J Clin Invest. 2010; 120(2):401-3. PMC: 2810093. DOI: 10.1172/JCI42088. View

16.

van de Geijn G, Hersmus R, Looijenga L . Recent developments in testicular germ cell tumor research. Birth Defects Res C Embryo Today. 2009; 87(1):96-113. DOI: 10.1002/bdrc.20140. View

17.

Tai M, Chang C, Kiupel M, Webster J, Olson L, Trosko J . Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis. 2004; 26(2):495-502. DOI: 10.1093/carcin/bgh321. View

18.

Trosko J . From adult stem cells to cancer stem cells: Oct-4 Gene, cell-cell communication, and hormones during tumor promotion. Ann N Y Acad Sci. 2007; 1089:36-58. DOI: 10.1196/annals.1386.018. View

19.

Feng D, Peng C, Li C, Zhou Y, Li M, Ling B . Identification and characterization of cancer stem-like cells from primary carcinoma of the cervix uteri. Oncol Rep. 2009; 22(5):1129-34. DOI: 10.3892/or_00000545. View

20.

Wang Y, Cai N, Wu X, Cao H, Xie L, Zheng P . OCT4 promotes tumorigenesis and inhibits apoptosis of cervical cancer cells by miR-125b/BAK1 pathway. Cell Death Dis. 2013; 4:e760. PMC: 3763434. DOI: 10.1038/cddis.2013.272. View