Heterogeneous ribonucleoprotein K is a marker of oral leukoplakia and correlates with poor prognosis of squamous cell carcinoma
Heterogeneous ribonucleoprotein K is a marker of oral leukoplakia and correlates with poor prognosis of squamous cell carcinoma
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DOI：
10.1002/ijc.24517
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发表时间：
2009-09-15
影响因子：
6.4
通讯作者：
Siu, K. W. Michael
中科院分区：
文献类型：
--
作者：
Matta, Ajay;Tripathi, Satyendra Chandra;Siu, K. W. Michael
口腔白斑是一种具有癌症发展风险的异质性病变；目前还没有生物标志物来预测其恶性转化的可能性。使用iTRAQ标记液相色谱-质谱法对口腔白斑进行组织蛋白质组学分析发现，与正常组织相比，白斑中异质核糖核蛋白K （hnRNP K）是一种转化相关的rna结合蛋白。在此，我们研究了hnRNP K在早期口腔白斑病变识别中的临床意义，以及作为头颈部/口腔鳞状细胞癌（HNOSCCs）的预后标志物。在100例HNOSCCs、199例白斑和55例非恶性组织中进行hnRNP K的免疫组化分析，并与HNOSCCs 6年临床病理参数和疾病预后相关。hnRNP - K核表达从正常组织到白斑和明显的恶性组织均升高（p < 0.001）。Kaplan-Meier分析显示，从白斑到HNOSCCs，细胞质hnRNP K显著升高（p < 0.001），且与HNOSCCs预后不良相关（p = 0.011）。我们随访研究中最重要的发现是细胞质hnRNP K是HNOSCC患者疾病复发的独立预测因子。总之，核hnRNP K可能作为早期诊断的潜在标志物，而其细胞质积累可以帮助识别预后不良的HNOSCC患者亚群，提示其在HNOSCC临床管理中的应用。(c) 2009年
Oral leukoplakia is a heterogeneous lesion with risk of cancer development; there are no biomarkers to predict its potential of malignant transformation. Tissue proteomic analysis of oral leukoplakia using iTRAQ labeling liquid chromatography-mass spectrometry showed overexpression of heterogeneous ribonucleo-protein K (hnRNP K), a transformation-related RNA-binding protein, in leukoplakia in comparison with normal tissue. Herein, we investigated the clinical significance of hnRNP K in identification of oral leukoplakic lesions in early stages and as a prognostic marker in head-and-neck/oral squamous cell carcinomas (HNOSCCs). Immunohistochemical analysis of hnRNP K was performed in 100 HNOSCCs, 199 leukoplakias and 55 nonmalignant tissues and correlated with clinicopathologic parameters and disease prognosis over 6 years for HNOSCCs. hnRNP K nuclear expression increased from normal tissues to leukoplakia, and frank malignancy (p < 0.001). Cytoplasmic hnRNP K increased significantly from leukoplakia to HNOSCCs (p < 0.001) and was associated with poor prognosis of HNOSCCs (p = 0.011) by Kaplan-Meier analysis. The most important finding of our follow-up study is that cytoplasmic hnRNP K is an independent predictor of disease recurrence in HNOSCC patients. In conclusion, nuclear hnRNP K may serve as a potential marker for early diagnosis, whereas its cytoplasmic accumulation can help to identify a subgroup of HNOSCC patients with poor prognosis, suggesting its putative utility in clinical management of HNOSCC. (C) 2009 UICC