Increased Expression of Oct4, Nanog and CD24 Predicts Poor Response to Chemo-Radiotherapy and Unfavourable Prognosis in Locally Advanced Oral Squamous Cell Carcinoma

Abstract

Background: Current study investigates the role of Oct4, Nanog and CD24 in locally-advanced oral squamous cell carcinoma (OSCC), to evaluate whether the expression of these markers can predict efficacy of neoadjuvantchemo-radiotherapy and survival of patients. Methods: Biomarker expression was evaluated in 50 homogenously treated patients of locally-advanced OSCC. Results: Clinical response was complete in 30% (n=15), partial response in 46% (n=23), no response in 24% (n=12). Pathologically, 74% patents (n=37) were responders and 26% were non-responders (n=13). Biomarker-overexpression was seen in 46% cases for Oct4, 54% cases for Nanog and 58% cases for CD24. Oct4, Nanog and CD24 expression showed significant correlation with clinical and pathological response (p<0.05). Three year recurrence-free survival was 71%, overall survival was 66%. Post-treatment advanced pathological N (ypN), post treatment advanced pathological TNM (ypTNM) stage, clinical non-response, pathologic non-response, positive/high expression of all three biomarkers had a significant negative impact on recurrence-free and overall survival. Conclusions: Expressions of Oct4, Nanog and CD24 have significant association with treatment response and survival in patients with locally advanced OSCC treated with neoadjuvant chemo-radiation. Survival of these patients is significantly affected by ypN stage, ypTNM stage, expression of all three biomarkers, clinical and pathological response to neoadjuvant therapy.

Spontaneous differentiation leads to emergence of hybrid cell states relate to poor prognosis in oral cancer

“…and Nanog was recently correlated with poor response to chemo-radio therapy and unfavorable prognosis in oral cancer [44]. Interestingly, Cisplatin selected oral cancer cell line was shown to express higher levels of Sox9 [35]; which is expressed at higher levels in CD44 +Ve /CD24 High /ALDH High subpopulation in our study, too.…”

“…Indeed in earlier studies, cells with CD24 High -phenotype marked a transient chemo-resistant cell state in lung cancer [28] and breast cancer [32]. Also, increased CD24 expression with Oct4 and Nanog is recently correlated with poor chemo-radio therapy response and unfavorable prognosis in oral cancer [43]. Interestingly, Cisplatin selected oral cancer cells were shown to express higher levels of Sox9 [34]; similar to high SOX9 expression in CD44 +Ve /CD24 High /ALDH High subpopulation in our study, too.…”

Emergence of hybrid states of stem-like cancer cells correlates with poor prognosis in oral cancer

“…Indeed; in earlier studies, cells with CD24 High -phenotype marked a transient chemo-resistant cell state in lung cancer ( Sharma et al., 2010 ) and breast cancer ( Goldman et al., 2015 ). Also, increased CD24 expression with OCT4 and NANOG is recently correlated with poor chemo-radiotherapy response and unfavorable prognosis in oral cancer ( Mishra et al., 2020 ). Therefore, phenotype switching may act as a robust mechanism for cancer cells to rapidly acquire a drug tolerant state in changing environment, from where these cells may eventually emerge as a drug-resistant population in relapsed tumor.…”

Cancer cell line microarray as a novel screening method for identification of radioresistance biomarkers in head and neck squamous cell carcinoma

“…Oct4 is a transcription factor essential for pluripotency in embryonic stem cells and testicular maturation. Oct4related stemness has been found to have a role in radiotherapy resistance of various cancers, including HNSCC [13,14,[33][34][35]. Especially interesting, regarding HNSC C, is that Oct4 expression is universally acknowledged to be a favourable biomarker for cisplatin sensitivity in testicular cancer, but seems to predict poor cisplatin response in other cancers [36][37][38].…”