Hasegawa Yasuhisa, Goto Mitsuo, Hanai Nobuhiro, Ijichi Kei, Terada Akihiro, Hyodo Ikuo, Ogawa Tetsuya, Fukushima Masakazu
Department of Head and Neck Surgery, Aichi Cancer Center, Nagoya, Japan.
Oncology. 2007;73(1-2):104-11. doi: 10.1159/000120998. Epub 2008 Mar 13.
The main purpose of the current study was to find predictive biomarkers that can be routinely used for the response to chemotherapy in head and neck squamous cell carcinoma (HNSCC).
From this standpoint, we selected the histoculture drug response assay (HDRA) to assess in vitro chemosensitivity, and real-time reverse transcription polymerase chain reaction to investigate the gene expression profile of individual tumors as available predictive biomarkers. Using both surgery and biopsy specimens, we analyzed their gene expression profiles using the 18 markers that we thought were likely predictors of the response to anti-cancer agents.
Statistically significant associations were found between 5-fluorouracil (5-FU) sensitivity in HDRA and HER-2 mRNA expression level (p = 0.0030). Moreover, HER-2 expression was significantly associated with cisplatin sensitivity (p = 0.0089). Cisplatin sensitivity in HDRA was also demonstrated to have a significant association with epidermal growth factor receptor (EGFR) expression in which the group with cisplatin resistance tended to have a higher expression level than the sensitive group (p = 0.0385).
HER-2 and EGFR may be possible reliable predictive biomarkers for anti-cancer therapy, and might help in the decision-making process for individual patients with HNSCC.
本研究的主要目的是寻找可常规用于预测头颈部鳞状细胞癌(HNSCC)化疗反应的生物标志物。
基于此观点,我们选择组织培养药物反应测定法(HDRA)来评估体外化疗敏感性,并采用实时逆转录聚合酶链反应来研究单个肿瘤的基因表达谱,作为可用的预测生物标志物。我们使用手术和活检标本,通过18种我们认为可能是抗癌药物反应预测指标的标志物来分析其基因表达谱。
在HDRA中5-氟尿嘧啶(5-FU)敏感性与HER-2 mRNA表达水平之间发现了具有统计学意义的关联(p = 0.0030)。此外,HER-2表达与顺铂敏感性显著相关(p = 0.0089)。HDRA中的顺铂敏感性还被证明与表皮生长因子受体(EGFR)表达存在显著关联,其中顺铂耐药组的表达水平往往高于敏感组(p = 0.0385)。
HER-2和EGFR可能是抗癌治疗中可靠的预测生物标志物,可能有助于HNSCC个体患者的决策过程。