Department of Otorhinolaryngology, University of Duisburg-Essen, Hufelandstrasse 55, 45127 Essen, Germany.
J Transl Med. 2011 Aug 21;9:139. doi: 10.1186/1479-5876-9-139.
Chronic inflammation plays an important role in head and neck squamous cell carcinomas (HNSCC). This study addresses the impact of two single nucleotide polymorphisms (SNP) Asp299Gly and Thr399Ile of the toll-like receptor (TLR) 4 gene on the clinical outcome while accounting for the influence of adjuvant systemic therapy in a large cohort of HNSCC patients.
Genotype analysis was done using DNA from tissue samples from 188 patients with HNSCC; TLR4 protein expression was assessed immunohistochemically in tissue microarrays. Classical survival models were used for statistical analyses.
Ten percent of patients with HNSCC presented with the TLR4 299Gly and 17% with the TLR4 399Ile allele. Patients with the heterozygous genotype TLR4 Asp299Gly had a significantly reduced disease-free and overall survival. Also, patients with the heterozygous genotype TLR4 Thr399Ile had a reduced disease-free survival. Notably, these associations seem to be attributable to relatively poor therapy response as e.g. reflected in a significantly shorter DFS among HNSCC patients carrying the Asp299Gly variant and receiving adjuvant systemic therapy.
According to this study, TLR4 299Gly und 399Ile alleles may serve as markers for prognosis of head and neck cancer in patients with adjuvant systemic therapy, particularly chemotherapy, and might indicate therapy resistance.
慢性炎症在头颈部鳞状细胞癌（HNSCC）中起着重要作用。本研究在考虑辅助全身治疗影响的情况下，研究了 Toll 样受体（TLR）4 基因的两个单核苷酸多态性（SNP）Asp299Gly 和 Thr399Ile 对临床结果的影响，在一个大型 HNSCC 患者队列中。
使用来自 188 例 HNSCC 患者组织样本中的 DNA 进行基因型分析；使用组织微阵列进行 TLR4 蛋白表达的免疫组织化学评估。使用经典生存模型进行统计分析。
10%的 HNSCC 患者携带 TLR4 299Gly 等位基因，17%的患者携带 TLR4 399Ile 等位基因。TLR4 Asp299Gly 杂合基因型患者的无病生存率和总生存率显著降低。此外，TLR4 Thr399Ile 杂合基因型患者的无病生存率降低。值得注意的是，这些关联似乎归因于相对较差的治疗反应，例如，在携带 Asp299Gly 变体并接受辅助全身治疗的 HNSCC 患者中，DFS 明显缩短。
根据这项研究，TLR4 299Gly 和 399Ile 等位基因可能作为接受辅助全身治疗，特别是化疗的头颈部癌症患者预后的标志物，并可能表明治疗耐药性。
