Expression of OCT4A: The First Step to the Next Stage of Urothelial Bladder Cancer Progression

Abstract

OCT4 (octamer-binding transcription factor) is a transcription factor responsible for maintaining the pluripotent properties of embryonic stem cells. In this paper, we present the results of studies to investigate the role of the OCT4 splicing variant in urothelial bladder cancer and the relationship between the OCT4 phenotype and the morphological parameters of tumor malignancy. Ninety patients who received a cystectomy for bladder cancer were enrolled. The expression of OCT4 protein was analyzed by immunohistochemistry. The ratio of OCT4-positive cells was the lowest in pT1 (pathological assessment (p)—tumor extent confined to mucosa (T1)) tumors and the highest in pTis (non-papillary tumor extent confined to urothelium) and pT2 (tumor extent including muscularis propria) tumors. Information about the percentage of OCT4A-positive tumor cells could facilitate choosing the treatment mode in borderline pTis–pT1 (crossing the border of the basement membrane; the first stage of progression) and pT1–pT2 (crossing the border of the muscularis propria; the second stage of progression) cases: a higher percentage of OCT4A-positive cells should support more radical therapy. A significantly higher percentage of cases with moderate OCT4 intensity was found in metastasizing (the third stage of progression) cases with >2 positive lymph nodes. The percentage of OCT4-positive cells was significantly higher for cancers with a high grade, higher non-classic differentiation number and greater aggressiveness of invasion. The differentiation, maturation and aggressiveness of tumor invasion appear to depend on the expression of the OCT4 phenotype in cancer cells, similar to the successive stages of malignancy progression in urothelial cancer.

Expression and Prognostic Value of Oct-4 in Astrocytic Brain Tumors

“…Although this may influence the TCGA mRNA results and the IHC results by Du et al[16] and Elsir et al[17], an increase of Oct-4 with grade seems to be a robust finding. Similar results have been obtained in oral cancer [28] and urothelial cancer [30] suggesting an association of Oct-4 with tumor malignancy in cancer in general.…”

Transcription factor Oct4 promotes osteosarcoma by regulating lncRNA AK055347

“…Oct4 was also reported to enhance lung cancer cell invasion and adhesion accompanied by the downregulation of epithelial marker cytokeratin and upregulation of the mesenchymal markers vimentin and neural cadherin (26). The percentage of OCT4-positive cells was significantly increased in higher grade, higher non-classic differentiation number and more invasive urothelial bladder cancer cases (27). Oct4 was also suggested to promote proliferation and invasion of esophageal cancer cells (8).…”

Epithelial plasticity in urothelial carcinoma: Current advancements and future challenges

“…Beta-catenin (β-catenin), signal transducer and activator of transcription 3, glioma associated oncogene 1, B lymphoma Mo-MLV insertion region 1 homolog (BMI1), POU domain, class 5, transcription factor 1/ octamer-binding transcription factor 4 (POU5F1/Oct4), sex determining region Y-box 2 (SOX2), Kruppel-like factor 4, v-myc myelocytomatosis viral oncogene homolog (avian) (MYC, formerly C-MYC) and NANOG are the oncogenes/transcription factors that have been observed to be responsible for maintaining the pluripotent properties of stem cells and aggressiveness of tumor invasion [5][6][7] . Studies on the identification of co-expression of keratin 5 and CD44 markers on UroCSCs distinguish them from differentiated tumor cells and support their basal-like phenotype.…”