Cancer Stem Cells and Stemness Markers in Oral Squamous Cell Carcinomas

Patel, Shanaya; Shah, Kanisha; Shah, Manoj; Kothari, Kiran; Rawal, Rakesh

doi:10.7314/apjcp.2014.15.20.8549

Cited by 44 publications

(52 citation statements)

References 73 publications

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“…However, to date, few CSC markers in OSCC have been identified (29,30). The results of the current study indicate that SOX2, KLF4 and brachyury may present clinically useful CSC markers, and their expression levels may be prognostic factors for OSCC.…”

Section: Discussionmentioning

confidence: 77%

Expression levels of SOX2, KLF4 and brachyury transcription factors are associated with metastasis and poor prognosis in oral squamous cell carcinoma

et al. 2015

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Abstract. The prognosis of oral squamous cell carcinoma (OSCC) patients is affected by tumor recurrence and metastasis, and cancer stem cells are hypothesized to be involved in these processes. Thus, the aim of the present study was to determine whether the expression levels of five stem cell-related transcription factors, sex determining region Y-box 2 (SOX2), octamer-binding transcription factor 4 (Oct4), avian myelocytomatosis viral oncogene homolog (c-Myc), Krüppel-like factor 4 (KLF4) and brachyury, are associated with metastasis and survival in OSCC. Immunohistochemistry was performed to analyze the expression of these proteins in biopsy specimens obtained from 108 OSCC patients. The results revealed that the expression of SOX2, Oct4, KLF4 and brachyury were significantly associated with lymph node metastasis (P=0.002, P=0.031, P=0.003 and P=0.007, respectively). In addition, the expression of KLF4 and brachyury were significantly associated with distant metastasis (P=0.014 and P=0.012, respectively). Furthermore, multivariate analysis revealed that SOX2 and KLF4 are predictive factors for lymph node metastasis [odds ratios (ORs), 4.526 and 4.851, respectively], and KLF4 is also a predictive factor for distant metastasis (OR, 9.607). In addition, OSCC patients with low co-expression of SOX2, KLF4 and brachyury exhibited a significantly lower disease-specific survival rate (78.6 vs. 100%; P=0.025; χ 2 =5.033) and disease-free survival rate (60.7 vs. 90.9%; P=0.015; χ 2 =5.897) when compared with OSCC patients with high co-expression of these factors. The results indicate that SOX2, KLF4 and brachyury serve important roles in tumor progression, and these transcription factors may thus represent clinically useful prognostic markers for OSCC.

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Section: Discussionmentioning

confidence: 77%

Expression levels of SOX2, KLF4 and brachyury transcription factors are associated with metastasis and poor prognosis in oral squamous cell carcinoma

et al. 2015

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“…137 This process also highlights the substanstial phenotypic and functional heterogeneity within CSCs that manifests as a continuum of stemness-related gene expression. 137,142 This heterogeneity might explain why definitive CSC markers are lacking, although major character istic pheno types are recognized. One could argue that radioresistance and reprogramming of CSCs add to the classic 4Rs and 5Rs that impact the outcome of a course of f ractionated radiotherapy, making a case for 6Rs.…”

Section: Cancer Stem Cells and Radiotherapymentioning

confidence: 98%

Opportunities and challenges of radiotherapy for treating cancer

2015

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The past 20 years have seen dramatic changes in the delivery of radiation therapy, but the impact of radiobiology on the clinic has been far less substantial. A major consideration in the use of radiotherapy has been on how best to exploit differences between the tumour and host tissue characteristics, which in the past has been achieved empirically by radiation-dose fractionation. New advances are uncovering some of the mechanistic processes that underlie this success story. In this Review, we focus on how these processes might be targeted to improve the outcome of radiotherapy at the individual patient level. This approach would seem a more productive avenue of treatment than simply trying to increase the radiation dose delivered to the tumour.

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“…Despite having a better understanding of cellular mechanisms during the carcinogenic process, the survival rates for patients with oral squamous cell carcinoma (OSCC) have not improved over the last decades . Late diagnosis, low treatment response, high recurrence rate, and regional metastases lead to a poor prognosis for those affected . Recently, many studies have focused on the identification of OSCC biomarkers, which can help with prognosis prediction and with choosing the best therapeutic approach for each patient…”

Section: Introductionmentioning

confidence: 99%