Gunduz Mehmet, Beder Levent Bekir, Gunduz Esra, Nagatsuka Hitoshi, Fukushima Kunihiro, Pehlivan Davut, Cetin Eren, Yamanaka Noboru, Nishizaki Kazunori, Shimizu Kenji, Nagai Noriyuki
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikatacho 2-5-1, Okayama, Japan.
Cancer Sci. 2008 Mar;99(3):531-8. doi: 10.1111/j.1349-7006.2007.00708.x. Epub 2007 Dec 15.
Although many clinical and pathological prognostic factors such as tumor stage and lymph-node involvement have been described, to date no reliable or clinically applicable marker or tumor aggressiveness has been identified for head and neck cancer. In an attempt to identify such a molecular prognostic marker, we analyzed the mRNA expression status of ING3 by quantitative reverse transcription-polymerase chain reaction. We also examined p53 mutation status and investigated its relationship with ING3, as well its clinicopathological characteristics. About half of the 71 tumor samples demonstrated downregulation of ING3 compared to their matched normal counterparts. Although most clinicopathological variables were not significantly related to ING3 downregulation or p53 mutation status, a significant relationship was detected in terms of overall survival between the cases with low and normal to high ING3 expression. At 5 years follow up, approximately 60% of the patients with normal to high ING3 expression survived, whereas this was 35% in the patients with low ING3 expression. Multivariate analysis also showed downregulation of ING3 as an independent prognostic factor for poor overall survival. These results reveal that ING3 would function as a potential tumor suppressor molecule and that low levels of ING3 may indicate an aggressive nature of head and neck cancer.
尽管已经描述了许多临床和病理预后因素,如肿瘤分期和淋巴结受累情况,但迄今为止,尚未确定用于头颈癌的可靠或临床适用的标志物或肿瘤侵袭性指标。为了确定这样一种分子预后标志物,我们通过定量逆转录-聚合酶链反应分析了ING3的mRNA表达状态。我们还检测了p53突变状态,并研究了其与ING3的关系以及临床病理特征。与匹配的正常样本相比,71个肿瘤样本中约有一半显示ING3表达下调。尽管大多数临床病理变量与ING3下调或p53突变状态无显著相关性,但在ING3低表达与正常至高表达的病例之间,总生存期存在显著相关性。在5年随访中,ING3正常至高表达的患者中约60%存活,而ING3低表达的患者中这一比例为35%。多变量分析还显示ING3下调是总生存期差的独立预后因素。这些结果表明,ING3可能作为一种潜在的肿瘤抑制分子发挥作用,ING3水平低可能表明头颈癌具有侵袭性。