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首页> 外文期刊>BMC Medical Genomics >Functional microarray analysis suggests repressed cell-cell signaling and cell survival-related modules inhibit progression of head and neck squamous cell carcinoma
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Functional microarray analysis suggests repressed cell-cell signaling and cell survival-related modules inhibit progression of head and neck squamous cell carcinoma

机译：功能性微阵列分析表明，受抑制的细胞信号转导和与细胞存活相关的模块抑制了头颈部鳞状细胞癌的进展

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Background Cancer shows a great diversity in its clinical behavior which cannot be easily predicted using the currently available clinical or pathological markers. The identification of pathways associated with lymph node metastasis (N+) and recurrent head and neck squamous cell carcinoma (HNSCC) may increase our understanding of the complex biology of this disease. Methods Tumor samples were obtained from untreated HNSCC patients undergoing surgery. Patients were classified according to pathologic lymph node status (positive or negative) or tumor recurrence (recurrent or non-recurrent tumor) after treatment (surgery with neck dissection followed by radiotherapy). Using microarray gene expression, we screened tumor samples according to modules comprised by genes in the same pathway or functional category. Results The most frequent alterations were the repression of modules in negative lymph node (N0) and in non-recurrent tumors rather than induction of modules in N+ or in recurrent tumors. N0 tumors showed repression of modules that contain cell survival genes and in non-recurrent tumors cell-cell signaling and extracellular region modules were repressed. Conclusions The repression of modules that contain cell survival genes in N0 tumors reinforces the important role that apoptosis plays in the regulation of metastasis. In addition, because tumor samples used here were not microdissected, tumor gene expression data are represented together with the stroma, which may reveal signaling between the microenvironment and tumor cells. For instance, in non-recurrent tumors, extracellular region module was repressed, indicating that the stroma and tumor cells may have fewer interactions, which disable metastasis development. Finally, the genes highlighted in our analysis can be implicated in more than one pathway or characteristic, suggesting that therapeutic approaches to prevent tumor progression should target more than one gene or pathway, specially apoptosis and interactions between tumor cells and the stroma.
机译：背景技术癌症的临床行为表现出极大的多样性，使用当前可用的临床或病理标记无法轻易预测。对与淋巴结转移（N +）和复发性头颈部鳞状细胞癌（HNSCC）相关的途径的识别可能会增加我们对这种疾病的复杂生物学的了解。方法从未经手术治疗的HNSCC患者中获取肿瘤样本。根据治疗（颈淋巴清扫术后放疗）后的病理淋巴结状态（阳性或阴性）或肿瘤复发（复发或非复发肿瘤）对患者进行分类。使用微阵列基因表达，我们根据相同途径或功能类别中的基因组成的模块筛选了肿瘤样品。结果最常见的改变是在阴性淋巴结（N0）和非复发性肿瘤中抑制模块，而不是在N +或复发性肿瘤中诱导模块。 N0肿瘤表现出抑制包含细胞存活基因的模块，在非复发性肿瘤中，细胞-细胞信号传导和细胞外区域模块被抑制。结论N0肿瘤中含有细胞存活基因的模块的阻遏增强了凋亡在转移调节中的重要作用。此外，由于此处未对肿瘤样品进行显微解剖，因此肿瘤基因表达数据与基质一起被表示出来，这可能揭示了微环境与肿瘤细胞之间的信号传导。例如，在非复发性肿瘤中，细胞外区域模块被抑制，表明基质和肿瘤细胞之间的相互作用可能较少，从而阻碍了转移的发展。最后，我们分析中突出显示的基因可能与多种途径或特征有关，这表明预防肿瘤进展的治疗方法应针对多种基因或途径，特别是凋亡和肿瘤细胞与基质之间的相互作用。

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