Oct-4: a prognostic biomarker of urinary bladder cancer in North India

Abstract

Background: The objective of this study was to evaluate Octamer-binding transcription factor 4 (Oct-4), neutrophil to lymphocyte ratio (NLR) and body mass index (BMI) as independent prognostic biomarkers for prediction of urinary bladder cancer (UBC) outcomes. With the advancement in prognostic biomarker discovery, tumor recurrence is difficult to accurately predict in UBC. UBC is costly to treat due to the requirement of frequent invasive follow-up sessions. Therefore, it is of utmost importance to evaluate good prognostic biomarkers for UBC surveillance. Methods: We studied 39 UBC tissue samples. Oct-4 protein expression was evaluated semiquantitatively by immunohistochemistry (IHC). Complete blood count data and body weight as well as the height of the patients were retrieved and recorded before the date of the first transurethral resection of bladder tumor (TURBT). The follow-up period was 48 months for recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS). Results: Oct-4 expression profile was found to be significantly associated with gender ( p = 0.028), tumor grade ( p = 0.038), tumor stage ( p = 0.003), lymph node status ( p = 0.029), recurrence ( p = 0.004), progression ( p = 0.011), and treatment modality ( p = 0.016). Tumor grade and progression were found significant with NLR values (tumor grade, p = 0.006; progression, p = 0.038) and BMI (tumor grade, p = 0.036; progression, p = 0.014). Moreover, BMI was also significantly associated with UBC recurrence ( p = 0.014). Kaplan–Meier survival analysis showed poor prognosis with both high Oct-4 expression (RFS, p = 0.001; PFS, p = 0.004; OS, p = 0.014) and high NLR values (RFS, p = 0.049; PFS, p = 0.004; OS, p = 0.005). Patients with high BMI too had poor RFS ( p = 0.025) and poor PFS ( p = 0.032). Furthermore, multivariate Cox regression analysis, indicated Oct-4 as an independent prognostic biomarker for RFS (HR = 0.240, 95% CI, 0.072–0.804, p = 0.021). Conclusions: We conclude that the expression profile of Oct-4 will be beneficial in prediction of UBC recurrence, and could have profound implications on the development of new therapeutic targets for UBC treatment.

High OCT4 Expression Might Be Associated with an Aggressive Phenotype in Rectal Cancer

“…Our results showed an absence of modulation of the expression of the stem cell marker OCT4 in adjacent non-tumor tissue, but did show OCT4 expression in tumor tissue consistent with other authors, who have reported OCT4 protein expression in various human cancer tissues such as stomach [9], pancreas [11], bladder [13], ovary [14], prostate [15], and CRC, but not in normal somatic tissues [38]. It is believed, then, that OCT4 reactivation occurs in cells that have undergone malignancy [30], in which the expression of pluripotency genes by stem cells has been related to tumor proliferation, metastasis, and poor prognosis [10].…”

“…Among the transcription factors described as regulators of pluripotency and maintenance of CSCs is the octamer-binding protein 4 (OCT4; also known as POU domain, class 5, transcription factor 1 (POU5F1)), an oncofetal protein that promotes self-renewal and maintenance of pluripotency of embryonic stem cells and induced stem cells, and which has been found to be involved in the progression and poor prognosis of various cancers [7], including gastric [8][9][10], pancreatic [11], breast [12], bladder [13], ovarian [14], prostate [15], and hepatocellular carcinoma [16]. However, few studies have included OCT4 evaluation in RC [17,18], and even fewer have evaluated its clinical significance in these patients [19].…”

Emerging Roles of Cancer Stem Cells in Bladder Cancer Progression, Tumorigenesis, and Resistance to Chemotherapy: A Potential Therapeutic Target for Bladder Cancer

“…Higher OCT4 expression in BC was shown to be linked with the higher grade of human BC and its recurrence after surgery [56]. Moreover, a recent study on 39 BC tissue samples in India revealed that OCT4 expression was correlated with gender, tumor grade, tumor stage, lymph node status, recurrence, progression, and treatment modality [57]. These data indicate that OCT4 could be a valuable clinical diagnostic and prognostic marker for the progression of BC and may become an attractive therapeutic target to establish new therapies for urothelial carcinoma.…”