The Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Transl Oncol. 2010 Aug 1;3(4):239-45. doi: 10.1593/tlo.10109.
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.
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。