Over-expression of MAGED4B increases cell migration and growth in oral squamous cell carcinoma and is associated with poor disease outcome

MAGE proteins have been shown to be good targets for cancer immunotherapy. We demonstrate that MAGED4B is over-expressed in more than 50% of Oral Squamous Cell Carcinoma (OSCC) tissues and the expression of MAGED4B is associated with lymph node metastasis and poor disease specific survival. OSCC cell lines that over-express MAGED4B promote migration in vitro, exhibit an increase in cell growth both in vitro and in vivo, and are more resistant to apoptosis compared to control cells. Our data suggest that MAGED4B over-expression is a driver in oral carcinogenesis and argues strongly that this protein may represent a potential therapeutic target in OSCC.     

Polymorphism in ADH and MTHFR genes in oral squamous cell carcinoma of Indians

Objectives: Alcohol consumption is known to increase the risk for several cellular disorders like oral cancer. The risk may be reinforced by polymorphism in genes like alcohol dehydrogenase. Therefore, this study is designed to asses the polymorphic status in ADH1B (formerly ADH2), ADH1C (formerly ADH3) and MTHFR genes in order to correlate the susceptibility to oral squamous cell carcinoma (OSCC). Subjects and methods: DNA from 126 OSCC samples were amplified using primers for ADH1B, ADH1C and MTHFR genes. The amplicons were analyzed for ADH1B*1, ADH1C*2 and MTHFR C677T allelic polymorphism by restriction digestion using appropriate enzymes. Results: ADH1B*1/*1 genotype in cancer patients who were heavy drinkers showed a negligible risk association with an odds ratio of 1.62; 95% CI = 1.08–2.14. In OSCC patients, ADH1C*2/*2 genotypes showed a relatively higher risk (odds ratio 2.65; 95% CI = 1.78–3.53) in heavy drinkers and a less significant risk (1.6; 95% CI = 1.15–2.03) in moderate drinkers and negligible risk in light drinkers (1.23; 95% CI = 0.77–1.63). In contrast, MTHFR 677TT genotype showed a high risk association for OSCC in heavy drinkers (odds ratio 3.0; 95% CI = 2.02–4.0). Interestingly, the combination of ADH1B*1/*1/ MTHFR 677TT genotypes in alcoholic cancer patients showed a high risk (odds ratio 4.16; 95% CI = 2.78–5.53). A similar risk (odds ratio 4.16; 95% CI = 1.18–5.53) was shown by ADH1B*1/*2/*2/*2MTHFR 677TT genotype combination. The ADH1C*2/*2 /MTHFR 677TT genotype combination showed the maximum risk (odds ratio 20; 95% CI = 13.45–26.64) in the heavy drinker group. This combination showed a high risk in moderate drinkers (odds ratio 5.88; 95% CI = 4.24–7.50) and relatively lower risk in light drinkers (odds ratio 2.77; 95% CI = 1.74–3.68). Conclusions: The ADH1C*2/*2/MTHFR 677TT genotype combination appears to be more susceptible for OSCC, since it showed a 20‐fold increase in risk in heavy drinkers and a 5.9‐ and 2.8‐fold increase in risk respectively in moderate drinkers and light drinkers. This study suggests the association of ADH1C*2/*2/MTHFR 677TT genotype combination as a risk factor for OSCC in alcoholics.     

Characteristics of a cancerous cell line, HIOEC-B(a)P-96, induced by benzo(a)pyrene from human immortalized oral epithelial cell line

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the oral and maxillofacial region. The mechanism of carcinogenesis of OSCC is still unclear. In vitro study on OSCC cell lines, especially derived from immortalized oral epithelial cells, is a very useful strategy to understand the mechanism of carcinogenesis. Based on our previous human immortalized oral epithelial cell (HIOEC) line, obtained from normal oral epithelial cells by transfection of HPV16 E6/E7 gene, a new cancerous cell line, HIOEC-B(a)P-96 (HB96), was established from the HIOEC by induction with benzo(a)pyrene. The characteristics of the HB96 cells such as cell morphology, ultrastructure, proliferation ability, invasion ability, and tumorigenesis were studied. The HB96 cells lost contact inhibition with uncontrolled cell division and obvious cell overlap, they were polygonal in shape and ununiform in size with increased ratio between nucleus and plasma. Increased proliferative ability and invasion ability were confirmed by the cell proliferation analysis and cell invasion assay, respectively. The tumorigenicity of well to moderately differentiated squamous cell carcinoma was confirmed in the nude mice experiments pathologically. Increased expression of HPV16 E6/E7 proteins and obvious correlation with decreased expression of p53 and Rb proteins was also confirmed by Western blotting. Thus, this HB96 cell line induced by benzo(a)pyrene from the HIOEC line is a useful tool to study the mechanism of carcinogenesis of OSCC in vitro for future genomic and proteomic analyses. It is also the first in vitro cancerous cell line of OSCC in China derived from immortalized oral epithelial cells.     

金黄地鼠颊囊癌变过程中COX-2,VEGF表达及相互关系的研究

目的 :环氧合酶 - 2 (cyclooxygenase- 2 ,COX - 2 )是催化前列腺素生物合成的限速酶 ,和许多肿瘤的形成与生长关系密切。本研究旨在探讨DMBA诱导金黄地鼠颊囊癌变过程中COX - 2的表达情况及其与血管内皮生长因子 (vascularendothelialgrowthfactor,VEGF)的关系。方法 :6周龄叙利亚品系金黄地鼠 6 0只 ,建立颊囊癌变的动物模型。然后用免疫组化的方法检测了COX - 2和VEGF的表达情况 ,并探讨COX - 2与VEGF关系。结果 :COX - 2在癌前病变、原位癌中高表达 ,与正常组织相比 ,其表达有显著差异 (P <0 .0 5 )。COX - 2不仅在癌细胞中表达 ,而且在癌组织及附近组织血管内皮细胞中表达。VEGF表达强度随着正常粘膜至鳞癌的发展逐渐增强。结论 :COX - 2在口腔鳞癌的发生、发展中起重要作用 ,与VEGF表达显著相关     

Differential expression of salivary S100A7 in oral submucous fibrosis

Aim

To investigate the expression of salivary S100A7 levels among patients with oral submucous fibrosis (OSF) and healthy controls.

非编码RNA在口腔癌中的研究进展

口腔癌是一种常见的头颈部恶性肿瘤,其发病的分子机制复杂且尚需进一步探索。非编码RNA占人类转录本的95%以上,是口腔癌发生发展机制研究的重要切入点,非编码RNA中数量庞大的microRNA、lncRNA和circRNA通过不同的途径参与了生物体内绝大部分的生理病理进程,与mRNA和蛋白质共同构成了一个复杂的调控体系。本文总结了口腔癌相关非编码RNA的研究文献及最新进展,从microRNA、lncRNA和circRNA三个方面为口腔癌的研究及防治提供参考。     

Does the geriatric nutrition risk index predict the prognosis of patients with oral squamous cell carcinoma?

Malnutrition is associated with the prognosis of malignant disease. The geriatric nutritional risk index (GNRI), based on serum albumin (ALB) levels and the present and ideal body weight, is a simple screening tool with which to predict the risk of malnutrition and mortality in patients. We hypothesised that nutritional markers could predict the prognosis of patients with oral squamous cell carcinoma (OSCC). The primary predictor variable was the GNRI score and the primary outcome variable was overall survival (OS). Univariate and multivariate analyses were performed using a Cox proportional hazard model to identify independent prognostic factors. The sample comprised 155 patients, of whom 17 presented with a low GNRI score (≤98) and 138 with a high GNRI score (≥ 98). There was a significant difference in OS when patients were stratified according to GNRI scores, with OS rates of 29.2% and 76.4% for scores of 98 and under and scores of over 98, respectively (p < 0.001). Univariate analyses showed that OS was significantly associated with GNRI score, age, T classification, N classification, stage, body mass index (BMI), prognostic nutrition index, and ALB levels. Analysis identified three independent predictive factors for OS: age (hazard ratio (HR) 2.184; 95% confidence interval (CI) 1.119 to 4.261; p = 0.022), stage (HR 2.684; 95% CI 1.457 to 5.367; p = 0.011), and GNRI score (HR 4.559; 95% CI 2.172 to 9.570; p <0.001). The results suggest that the GNRI score (>98 vs ≤98) is a good prognostic marker in patients with OSCC, along with age and stage.     

Parathyroid hormone-related protein serves as a prognostic indicator in oral squamous cell carcinoma

Background

In our previous study, parathyroid hormone-like hormone (PTHLH) which encodes parathyroid hormone-related protein (PTHrP) was revealed to be up-regulated in oral squamous cell carcinoma (OSCC) compared with paired apparently normal surgical margins using microarray method. However, the function and prognostic indicators of PTHLH/PTHrP in OSCC remain obscure.

Methods

The mRNA levels of PTHLH and its protein levels were investigated in 9 OSCC cell lines and in 36 paired OSCC specimens by real-time PCR and western blotting. The biological function of PTHLH/PTHrP was investigated using small interfering RNA (siRNA) in 3 OSCC cell lines, and immunohistochemistry was used to estimate the prognostic value of PTHrP in 101 patients with head and neck squamous cell carcinoma (HNSCC), including OSCC and oropharyngeal squamous cell carcinoma. Cell cycle was tested by flow cytometry and cell cycle related genes were investigated by western blotting and immunocytochemistry assay.

Results

This study showed that the mRNA and protein levels of PTHLH in 9 OSCC cell lines were much higher than that in normal epithelial cells (P < 0.0001). In 36 paired OSCC tissues, PTHLH mRNA expressions were found higher in 32 OSCC tissues than that of paired apparently normal surgical margins (P = 0.0001). The results revealed that the down-regulation of PTHLH/PTHrP by siRNAs could reduce cell proliferation and inhibit plate and soft agar colony formation as well as affect the cell cycle of OSCC cells. The key proteins related to the cell cycle were changed by anti-PTHLH siRNA. The results showed that cyclin D1 and CDK4 expressions were significantly reduced in the cells transfected with anti-PTHLH siRNA. On the other hand, the expression of p21 was increased. The results also showed that high PTHrP level was associated with poor pathologic differentiation (P = 0.0001) and poor prognosis (P = 0.0003) in patients with HNSCC.

Conclusions

This study suggests that PTHLH/PTHrP is up-regulated in OSCCs. Therefore, PTHLH/PTHrP could play a role in the pathogenesis of OSCC by affecting cell proliferation and cell cycle, and the protein levels of PTHrP might serve as a prognostic indicator for evaluating patients with HNSCCs.