OCT4 but not SOX2 expression correlates with worse prognosis in surgical patients with triple-negative breast cancer
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Octamer-binding transcription factor 4 (OCT4) and SRY (sex determining region Y)-box 2 (SOX2) are common biomarkers of cancer stem cells, which contribute to the pathological processes of several carcinomas, while little is known about the effects of OCT4 and SOX2 on the prognosis of triple-negative breast cancer (TNBC). The purpose was to evaluate the correlation of tumor tissue OCT4 and SOX2 expressions with clinicopathological features and overall survival (OS) in surgical TNBC patients.
127 surgical patients with TNBC were enrolled in this cohort study. Tumor tissue samples were obtained during the operation. OCT4 and SOX2 expressions were assessed by immunofluorescent staining.
32 (25%) TNBC patients with OCT4 positive expression (OCT4+), 21 (17%) patients with SOX2 positive expression (SOX2+), and 11 (9%) patients with both OCT4+ and SOX2+ were observed. OCT4 expression was positively associated with histologic grade (P < 0.001), pathological tumor size (P = 0.014), N stage (P < 0.001) and TNM stage (P < 0.001), while SOX2 expression was positively correlated with histologic grade (P < 0.001), pathological tumor size (P = 0.033) and Ki-67 expression (P = 0.016). Kaplan–Meier (K–M) curves suggested OCT4+ was correlated with shorter OS compared with OCT4− (P < 0.001), while no correlation between SOX2+ with OS in all patients (P = 0.128) was observed. Multivariate Cox model indicated that OCT4+ (P < 0.001) were independent factors for worse OS.
Tumor tissue OCT4 but not SOX2 expression was positively correlated with histologic grade, pathological tumor size, N stage and TNM stage, and it could be served as an independent biomarker to predict worse prognosis in surgical patients with TNBC.
KeywordsTumor tissue OCT4 SOX2 Prognosis Triple-negative breast cancer
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in this study were in accordance with the ethical standards of the institutional ethics committee and with the 1964 Helsinki declaration and its later amendments.
Informed consent was obtained from all individual participants included in the study.
- 5.Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121(7):2750–67. https://doi.org/10.1172/JCI45014.CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Kashyap V, Rezende NC, Scotland KB, Shaffer SM, Persson JL, Gudas LJ, et al. Regulation of stem cell pluripotency and differentiation involves a mutual regulatory circuit of the NANOG, OCT4, and SOX2 pluripotency transcription factors with polycomb repressive complexes and stem cell microRNAs. Stem Cells Dev. 2009;18(7):1093–108. https://doi.org/10.1089/scd.2009.0113.CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Hu J, Qin K, Zhang Y, Gong J, Li N, Lv D, et al. Downregulation of transcription factor OCT4 induces an epithelial-to-mesenchymal transition via enhancement of Ca2+ binflux in breast cancer cells. Biochem Biophys Res Commun. 2011;411(4):786–91. https://doi.org/10.1016/j.bbrc.2011.07.025.CrossRefPubMedGoogle Scholar
- 25.Gwak JM, Kim M, Kim HJ, Jang MH, Park SY. Expression of embryonal stem cell transcription factors in breast cancer: OCT4 as an indicator for poor clinical outcome and tamoxifen resistance. Oncotarget. 2017;8(22):36305–18. https://doi.org/10.18632/oncotarget.16750.CrossRefPubMedPubMedCentralGoogle Scholar
- 32.Yong X, Tang B, Xiao YF, Xie R, Qin Y, Luo G, et al. Helicobacter pylori upregulates Nanog and OCT4 via Wnt/beta-catenin signaling pathway to promote cancer stem cell-like properties in human gastric cancer. Cancer Lett. 2016;374(2):292–303. https://doi.org/10.1016/j.canlet.2016.02.032.CrossRefPubMedGoogle Scholar
- 38.Hui K, Gao Y, Huang J, Xu S, Wang B, Zeng J, et al. RASAL2, a RAS GTPase-activating protein, inhibits stemness and epithelial–mesenchymal transition via MAPK/SOX2 pathway in bladder cancer. Cell Death Dis. 2017;8(2):e2600. https://doi.org/10.1038/cddis.2017.9.CrossRefPubMedPubMedCentralGoogle Scholar
- 41.Shen L, Huang X, Xie X, Su J, Yuan J, Chen X. High expression of SOX2 and OCT4 indicates radiation resistance and an independent negative prognosis in cervical squamous cell carcinoma. J Histochem Cytochem. 2014;62(7):499–509. https://doi.org/10.1369/0022155414532654.CrossRefPubMedPubMedCentralGoogle Scholar