S100A7 overexpression is a predictive marker for high risk of malignant transformation in oral dysplasia
S100A7 overexpression is a predictive marker for high risk of malignant transformation in oral dysplasia
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DOI：
10.1002/ijc.28473
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发表时间：
2014-03-15
影响因子：
6.4
通讯作者：
Ralhan, Ranju
中科院分区：
文献类型：
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作者：
Kaur, Jatinder;Matta, Ajay;Ralhan, Ranju
早期发现口腔病变（OL）在癌症发展的高风险是最重要的干预。对于能够识别高风险OL的生物标志物，存在迫切的未满足的临床需求。最近，我们使用蛋白质组学鉴定并验证了一组五种候选蛋白质生物标志物，即S100 A7、胸腺素原α、14-3-3、14-3-3 σ和异质核核糖核蛋白K，以区分具有异型增生和口腔癌的OL与正常口腔组织。本研究的目的是评估这些候选蛋白质生物标志物用于识别具有高癌症发展风险的口腔异型增生病变的潜力。使用免疫组织化学，我们分析了这五个候选蛋白质生物标志物在110例活检证实的口腔发育不良和已知的临床结果，并确定其与p16表达和HPV 16/18状态的相关性。Kaplan-Meier生存分析显示，与细胞质中S100 A7免疫染色较弱或无S100 A7免疫染色的患者（平均OCFS = 122.8个月）相比，细胞质中S100 A7过表达的患者的口腔无癌生存期（OCFS）减少68.6个月（p = 0.007）。多变量考克斯回归分析显示，细胞质S100 A7过表达是与异型增生病变中癌症发展相关的最重要的候选标志物（p = 0.041，风险比= 2.36）。总之，我们的研究表明S100 A7过表达在识别具有高度癌症发展风险的异型增生的OL中的潜力。口腔病变与异型增生的恶性转化的高风险的识别仍然是一个重大的临床挑战，是最重要的识别患者谁将受益于早期干预。目前，临床上还没有常规使用的生物标志物来预测高危病变。在这里，作者评估了五种候选蛋白质生物标志物的潜力，并将其表达与p16和HPV 16/18相关联，以识别具有癌症发展高风险的口腔病变。S100 A7过表达显示了作为评估口腔发育不良进展为癌症的风险的有用标志物的潜力。
Early detection of oral lesions (OLs) at high risk of cancer development is of utmost importance for intervention. There is an urgent unmet clinical need for biomarkers that allow identification of high-risk OLs. Recently, we identified and verified a panel of five candidate protein biomarkers namely S100A7, prothymosin alpha, 14-3-3, 14-3-3 sigma and heterogeneous nuclear ribonucleoprotein K using proteomics to distinguish OLs with dysplasia and oral cancers from normal oral tissues. The objective of our study was to evaluate the potential of these candidate protein biomarkers for identification of oral dysplastic lesions at high risk of cancer development. Using immunohistochemistry, we analyzed expressions of these five candidate protein biomarkers in 110 patients with biopsy-proven oral dysplasia and known clinical outcome and determined their correlations with p16 expression and HPV 16/18 status. Kaplan-Meier survival analysis showed reduced oral cancer-free survival (OCFS) of 68.6 months (p = 0.007) in patients showing cytoplasmic S100A7 overexpression when compared to patients with weak or no S100A7 immunostaining in cytoplasm (mean OCFS = 122.8 months). Multivariate Cox regression analysis revealed cytoplasmic S100A7 overexpression as the most significant candidate marker associated with cancer development in dysplastic lesions (p = 0.041, hazard ratio = 2.36). In conclusion, our study suggested the potential of S100A7 overexpression in identifying OLs with dysplasia at high risk of cancer development.What's new? Identification of oral lesions with dysplasia at high risk of malignant transformation remains a major clinical challenge, and is of utmost importance for identifying patients who would benefit from early intervention. Currently, there are no biomarkers that are being routinely used in clinics to predict high-risk lesions. Here, the authors evaluated the potential of five candidate protein biomarkers and correlated their expression with p16 and HPV 16/18 to identify oral lesions with dysplasia at high risk of cancer development. S100A7 overexpression demonstrated the potential to serve as a useful marker for estimating the risk of oral dysplasia progressing to cancer.