ITGA3 and ITGB4 expression biomarkers estimate the risks of locoregional and hematogenous dissemination of oral squamous cell carcinoma.

ITGA3 and ITGB4 expression biomarkers estimate the risks of locoregional and hematogenous dissemination of oral squamous cell carcinoma.
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DOI:
10.1186/1471-2407-13-410
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发表时间:
2013-09-05
期刊:
影响因子:
3.8
通讯作者:
Takagi R
Takagi R
中科院分区:
医学2区
文献类型:
--
作者:
Nagata M;Noman AA;Suzuki K;Kurita H;Ohnishi M;Ohyama T;Kitamura N;Kobayashi T;Uematsu K;Takahashi K;Kodama N;Kawase T;Hoshina H;Ikeda N;Shingaki S;Takagi R

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分子生物学标志物对于监测口腔鳞状细胞癌的治疗效果、预测预后、提高生存率至关重要。本研究旨在验证两种整合素基因表达比率作为生物标志物的有效性。应用实时荧光定量PCR技术对270例口腔鳞癌组织总RNA中整合素α3(ITGA 3)、整合素β4(ITGB 4)、CD 9抗原(CD 9)和斑珠蛋白(JUP)基因表达进行分析。对ITGA 3/CD 9和ITGB 4/JUP的基因表达比以及主要临床事件的临床病理学参数进行了对数秩检验、考克斯比例风险模型和Kaplan-Meier估计。高ITGA 3/CD 9比值(high-ITGA 3/CD 9)和浸润性组织病理学(YK 4)病例的淋巴结转移率高(约80%)。原发部位复发(PSR)与高ITGA 3/CD 9、T3-4(TNM分级)和阳性切缘相关,表明PSR受治疗失败和生物学恶性肿瘤的协同影响。高ITGB 4/JUP比率(high-ITGB 4/JUP)被揭示为远处转移的主要贡献者,而不涉及临床病理因素,这表明依赖于整合素β4亚基功能的关键步骤的干预。Kaplan-Meier曲线显示,在ITGA 3/CD 9和YK 4双阳性病例中,阳性边缘是致命的治疗结果。OSCC的转移特点有两种:以ITGA 3/CD 9高表达为特征的局部播散和以ITGB 4/JUP高表达为特征的血行播散。整合素生物标志物的临床意义意味着生物学机制,如癌细胞运动和锚定非依赖性生存是至关重要的口腔鳞癌复发和转移。
Molecular biomarkers are essential for monitoring treatment effects, predicting prognosis, and improving survival rate in oral squamous cell carcinoma. This study sought to verify the effectiveness of two integrin gene expression ratios as biomarkers. Gene expression analyses of integrin α3 (ITGA3), integrin β4 (ITGB4), CD9 antigen (CD9), and plakoglobin (JUP) by quantitative real-time PCR were conducted on total RNA from 270 OSCC cases. The logrank test, Cox proportional hazards model, and Kaplan-Meier estimates were performed on the gene expression ratios of ITGA3/CD9 and ITGB4/JUP and on the clinicopathological parameters for major clinical events. A high rate (around 80%) of lymph node metastasis was found in cases with a high ITGA3/CD9 ratio (high-ITGA3/CD9) and invasive histopathology (YK4). Primary site recurrence (PSR) was associated with high-ITGA3/CD9, T3-4 (TNM class), and positive margin, indicating that PSR is synergistically influenced by treatment failure and biological malignancy. A high ITGB4/JUP ratio (high-ITGB4/JUP) was revealed to be a primary contributor to distant metastasis without the involvement of clinicopathological factors, suggesting intervention of a critical step dependent on the function of the integrin β4 subunit. Kaplan-Meier curves revealed positive margin as a lethal treatment consequence in high-ITGA3/CD9 and YK4 double-positive cases. Two types of metastatic trait were found in OSCC: locoregional dissemination, which was reflected by high-ITGA3/CD9, and distant metastasis through hematogenous dissemination, uniquely distinguished by high-ITGB4/JUP. The clinical significance of the integrin biomarkers implies that biological mechanisms such as cancer cell motility and anchorage-independent survival are vital for OSCC recurrence and metastasis.
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