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高 SEPT9_v1 表达与头颈部鳞状细胞癌的不良临床结局相关。

High SEPT9_v1 Expression Is Associated with Poor Clinical Outcomes in Head and Neck Squamous Cell Carcinoma.

机构信息

The Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.

出版信息

Transl Oncol. 2010 Aug 1;3(4):239-45. doi: 10.1593/tlo.10109.

Abstract

The purpose of this work was to determine SEPT9_v1 expression levels in head and neck squamous cell carcinoma (HNSCC) and to analyze whether SEPT9_v1 expression is relevant to clinical outcomes. Recently, the SEPT9 isoform SEPT9_v1 has been implicated in oncogenesis, and methylation of the SEPT9 promoter region was reported in HNSCC. These findings led us to hypothesize that SEPT9_v1 could be differently expressed in HNSCC. To determine whether SEPT9_v1 is expressed in HNSCC, tissue microarray immunohistochemical analysis was performed using a SEPT9_v1-specific antibody. Tissue microarrays stained with a polyclonal SEPT9_v1-specific antibody was used to determine protein expression levels in HNSCC tissue samples, some with known clinical outcomes. This analysis showed that SEPT9_v1 is in fact highly expressed in HNSCC compared with normal epithelium, and high expression levels directly correlated with poor clinical outcomes. Specifically, a high SEPT9_v1 expression was associated with decreased disease-specific survival (P = .012), time to indication of surgery at primary site (P = .008), response to induction chemotherapy (P = .0002), and response to chemotherapy (P = .02), as well as advanced tumor stage (P = .012) and N stage (P = .0014). The expression of SEPT9_v1 was also strongly correlated with smoking status (P = .00094). SEPT9_v1 is highly expressed in HNSCC, and a high expression of SEPT9_v1 is associated with poor clinical outcomes. These data indicate that SEPT9_v1 warrants additional investigation as a potential biomarker for HNSCC.

摘要

这项工作的目的是确定头颈部鳞状细胞癌(HNSCC)中 SEPT9_v1 的表达水平,并分析 SEPT9_v1 的表达是否与临床结局相关。最近,SEPT9 同种型 SEPT9_v1 被认为与肿瘤发生有关,并且在 HNSCC 中报道了 SEPT9 启动子区域的甲基化。这些发现使我们假设 SEPT9_v1 可能在 HNSCC 中表达不同。为了确定 SEPT9_v1 是否在 HNSCC 中表达,使用 SEPT9_v1 特异性抗体进行组织微阵列免疫组织化学分析。使用针对 SEPT9_v1 的多克隆特异性抗体对组织微阵列进行染色,以确定 HNSCC 组织样本中的蛋白表达水平,其中一些具有已知的临床结局。这项分析表明,与正常上皮相比,SEPT9_v1 在 HNSCC 中实际上高度表达,并且高表达水平与不良的临床结局直接相关。具体而言,高 SEPT9_v1 表达与疾病特异性生存降低相关(P=0.012)、原发部位手术指征的时间(P=0.008)、诱导化疗反应(P=0.0002)、化疗反应(P=0.02)以及晚期肿瘤分期(P=0.012)和 N 分期(P=0.0014)。SEPT9_v1 的表达也与吸烟状态强烈相关(P=0.00094)。SEPT9_v1 在 HNSCC 中高度表达,并且 SEPT9_v1 的高表达与不良的临床结局相关。这些数据表明,SEPT9_v1 作为 HNSCC 的潜在生物标志物值得进一步研究。

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