Chin David, Boyle Glen M, Williams Rebecca M, Ferguson Kaltin, Pandeya Nirmala, Pedley Julie, Campbell Catherine M, Theile David R, Parsons Peter G, Coman William B
Melanoma Genomics Group, Queensland Institute of Medical Research, Herston, Brisbane, Queensland, Australia.
Int J Cancer. 2005 Feb 20;113(5):789-97. doi: 10.1002/ijc.20608.
Head and neck cancer (HNSCC) is one of the most distressing human cancers, causing pain and affecting the basic survival functions of breathing and swallowing. Mortality rates have not changed despite recent advances in radiotherapy and surgical treatment. We have compared the expression of over 13,000 unique genes in 7 cases of matched HNSCC and normal oral mucosa. Of the 1,260 genes that showed statistically significant differences in expression between normal and tumor tissue at the mRNA level, the three top ranking of the top 5% were selected for further analysis by immunohistochemistry on paraffin sections, along with the tumor suppressor genes p16 and p53, in a total of 62 patients including 55 for whom >4-year clinical data was available. Using univariate and multivariate survival analysis, we identified SPARC/osteonectin as a powerful independent prognostic marker for short disease-free interval (DFI) (p < 0.002) and poor overall survival (OS) (p = 0.018) of HNSCC patients. In combination with other ECM proteins found in our analysis, PAI-1 and uPA, the association with DFI and OS became even more significant (p < 0.001). Our study represents the first instance of SPARC as an independent prognostic marker in HNSCC.
头颈癌（HNSCC）是最令人痛苦的人类癌症之一，会引发疼痛并影响呼吸和吞咽等基本生存功能。尽管放疗和手术治疗近期有所进展，但死亡率并未改变。我们比较了7例匹配的头颈癌和正常口腔黏膜中超过13000个独特基因的表达情况。在mRNA水平上，正常组织和肿瘤组织之间表达存在统计学显著差异的1260个基因中，选取前5%中排名最靠前的三个基因，连同肿瘤抑制基因p16和p53，在总共62例患者（其中55例有超过4年的临床数据）的石蜡切片上进行免疫组织化学进一步分析。通过单因素和多因素生存分析，我们确定富含半胱氨酸的酸性分泌蛋白/骨连接蛋白（SPARC/osteonectin）是头颈癌患者无病生存期（DFI）短（p < 0.002）和总生存期（OS）差（p = 0.018）的有力独立预后标志物。在我们的分析中，与其他细胞外基质蛋白纤溶酶原激活物抑制剂-1（PAI-1）和尿激酶型纤溶酶原激活剂（uPA）相结合，与无病生存期和总生存期的关联变得更加显著（p < 0.001）。我们的研究首次表明SPARC是头颈癌的独立预后标志物。
