Marker For Oral Squamous Cell Carcinoma Research Articles

The chemokine receptor CXCR4 demonstrates several features of a cancer stem cell marker in OSCC

Introduction: The concept of cancer stem cells (CSCs) has accumulated plenty of recent evidence derived from work on solid epithelial tumours such as breast, ovary, prostate and lung. The chemokine receptor CXCR4 and its ligand SDF-1 have been identified as key to normal stem cell tissue homing and their role in CSC populations is suggested. The aim of this study was to investigate the possibility of the SDF1-CXCR4 axis defining a population of CSCs in oral squamous cell carcinoma (OSCC).

Decreased expression of Annexin A1 correlates with pathologic differentiation grade in oral squamous cell carcinoma

Previously, we established an in vitro cellular carcinogenesis model of oral squamous cell carcinoma (OSCC), including the human immortalized oral epithelia cells (HIOECs) and its derived cancerous HB96 cells. In this study, comparative proteomic analysis identified that Annexin A1 was one of the significantly down-regulated genes in the cancerous HB96 cells. To investigate Annexin A1 down-regulation and its potential usefulness as a molecular marker in OSCC, we further screened Annexin A1 expressions with a panel of OSCC lines, and clinical samples of cancerous and the paired adjacent normal tissues from primary OSCC patients. By Western blot analysis and real-time PCR, we showed that both Annexin A1 mRNA and protein expressions decreased in OSCC cell lines except in two cell lines for the mRNA levels. Immunohistochemistry and real-time PCR also showed that both Annexin A1 mRNA and protein expressions decreased in the cancerous tissues from OSCC patients compared with those in the paired adjacent non-malignant epithelia. More importantly, both Annexin A1 mRNA and protein expressions negatively correlated with the pathologic differentiation grades of cancerous tissues. The lower Annexin A1 mRNA or protein expressions correlated with the poorer pathologic differentiation grades. These results suggest that decreased expression of Annexin A1 contributes to the cancerous progression of OSCC, and Annexin A1 may be a potential biomarker for pathologic differentiation grade of OSCC.

Prognostic significance of 14-3-3σ expression in oral squamous cell carcinoma (OSCC)

14-3-3sigma an intracellular phosphoserine binding protein regulates different cellular signalling processes and is involved in cancer development. In this study, we examined the expression of 14-3-3sigma and evaluated its clinical significance in OSCC. Tumour tissue from 95 OSCC patients was analysed for 14-3-3sigma and p53 expression, respectively. The correlation of these proteins with survival and clinical parameters was assessed. 14-3-3sigma high expression was observed in 44.2% of OSCC patients. A significant role of 14-3-3sigma expression on survival was shown by Kaplan-Meier analysis. Median survival time was 4.1years for patients with 14-3-3sigma low tumours, compared with 1.36years for 14-3-3sigma high tumours (P=.0021). Subset analysis in patients receiving adjuvant chemotherapy showed that the overall survival was significantly decreased in 14-3-3sigma high tumours than in 14-3-3sigma low tumours (P=.02). p53 expression was not significant in univariate analyses. In multivariate regression analysis, 14-3-3sigma expression emerged as a significant independent parameter (P=.003). These results provide evidence that 14-3-3sigma expression is involved in OSCC and, in contrast to p53 expression represents a new prognostic marker for OSCC and therapy response. Pending validation targeting 14-3-3sigma might also be a new opportunity to improve therapy.

RNA from brush oral cytology to measure squamous cell carcinoma gene expression

RNA expression analysis of oral keratinocytes can be used to detect early stages of disease such as oral cancer or to monitor on-going treatment responses of the same or other oral diseases. A limitation is the inability to obtain high quality RNA from oral tissue without using biopsies. While oral cytology cell samples can be obtained from patients in a minimally invasive manner they have not been validated for quantitative analysis of RNA expression. As a starting point in the analysis of tumor markers in oral squamous cell carcinoma (OSCC), we examined RNA in brush cytology samples from hamsters treated with dibenzo[a,l]pyrene to induce oral carcinoma. Three separate samples from each animal were assessed for expression of candidate marker genes and control genes measured with real-time RT-PCR. Brush oral cytology samples from normal mucosa were shown to consist almost exclusively of epithelial cells. Remarkably, ss-2 microglobulin and cytochrome p450, 1B1 (CYP1B1) RNA showed potential utility as markers of OSCC in samples obtained in this rapid and non-surgical manner. Brush oral cytology may prove useful as a source of RNA for gene expression analysis during the progression of diseases of the oral epithelium such as OSCC.

Expression of oncofoetal marker carcinoembryonic antigen in oral cancers in South India—a pilot study

Expression of the oncofoetal glycoprotein, carcinoembryonic antigen (CEA), has been observed in a number of malignancies and is also being pursued as a target for anti-cancer therapy. This study explored the status of this biochemical entity in the oral squamous cell carcinoma (SCC) in South India caused by extensive chewing habits. Squamous cell carcinoma in the study belonged to grade I and grade II. Tumour staging of the patients recruited in the study ranged from T2N1M0 to T4N3M0. Of the grade II cases studied, 88% (7 out of 8) showed expression of CEA. The 2 cases of grade I SCC of buccal mucosa also showed positive anti-CEA staining. If the results from this pilot study can be validated with a larger sample size, a role can be attributed to this tumour marker in oral neoplasia, thereby opening up avenues for using CEA as an additional diagnostic marker in oral SCC in this population and as a possible target for anti-cancer therapy.

High stromal versican expression predicts unfavourable outcome in oral squamous cell carcinoma

Background: Versican, an extracellular matrix proteoglycan, has been noted to be expressed in several malignant tumours and has been suggested to play an important role in cancer development and tumour...

Telomerase activity in oral squamous cell carcinoma and leukoplakia

Telomeres, the physical ends of eukaryotic chromosomes, are important to stabilize the chromosome and have a unique simple repetitive DNA sequence, TTAGGG in humans. In most normal somatic cells, telomere length becomes 50-100 bp shorter with every cell division, and the cells finally go into senescence, while most cancer cells have been reported to maintain the length and thus are immortalized. Telomeres are replicated by a special transcriptase, called telomerase, which is composed of a template RNA (hTR) and at least two component proteins: hTERT (hEST 2/hTRT) and hTEP 1 (hTLP 1/hTP1). In the present paper, I examined the status of telomerase activities in oral squamous cell carcinomas (OSCCs), precancerous lesions, and also cell lines established from OSCCs, by using a non-radioactive PCR-based TRAP (telomeric repeat amplification protocol) assay. Telomerase activities were detected in 23 of 30 OSCCs, 8 of 17 leukoplakias, 0 of 5 normal tissues, and in 8 of 8 OSCC cell lines and 0 of 5 normal human keratinocyte cultures. These results indicated that telomerase activity might have some association with carcinogenesis and might be used as a tumor marker in OSCC.

Overexpression of insulin-like growth factor binding protein 3 in oral squamous cell carcinoma

Previously, we established an in vitro cellular carcinogenesis model of oral squamous cell carcinoma (OSCC), including a human immortalized oral epithelial cell (HIOEC) line and its derived cancerous HB96 cell line. Further cDNA microarray analysis showed a significant up-regulated gene, insulin-like growth factor binding protein 3 (IGFBP3), accompanying with in vitro cancerization from HIOEC to HB96. In order to investigate IGFBP3 up-regulation and its potential usefulness as a molecular marker in OSCC, we detected the IGFBP3 expression with a panel of OSCC lines, and clinical samples of cancerous tissues and paired adjacent non-malignant epithelia from primary OSCC patients. Western blotting and real-time PCR showed increased IGFBP3 mRNA level and protein expression in OSCC cell lines compared with HIOEC in vitro; immunohistochemistry and real-time PCR also showed increased IGFBP3 mRNA level and protein expression in cancerous tissues compared with adjacent non-malignant epithelia from OSCC patients. Positive correlations were found between the IGFBP3 protein-positive grade in cancerous tissue and the tumor size as well as lymph node metastasis, a larger tumor size and positive lymph node metastasis indicating a higher level of IGFBP3 protein-positive grade. Based on these results, IGFBP3 may be used as a positive biomarker for OSCC development and progression.