Fibronectin 1 is a potential biomarker for radioresistance in head and neck squamous cell carcinoma
Fibronectin 1 is a potential biomarker for radioresistance in head and neck squamous cell carcinoma
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DOI：
10.4161/cbt.10.12.13432
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发表时间：
2010-12-15
影响因子：
3.6
通讯作者：
Roberg, Karin
中科院分区：
文献类型：
--
作者：
Jerhammar, Fredrik;Ceder, Rebecca;Roberg, Karin
放射治疗仍然是头颈部癌症治疗的支柱，但肿瘤的放射抵抗有时会阻碍治疗效果。确定放射治疗反应的预测生物标志物是走向个性化治疗的关键一步。本研究的目的是探索基因表达数据，以寻找预测头颈部鳞状细胞癌(HNSCC)放射治疗反应的生物标志物。从29个HNSCC细胞系中选择5个具有不同内在放射敏感性的细胞株进行微阵列分析。生物信息学方法包括基因本体论(GO)、富集谱和独创性路径分析(IPA)。GO-分析检测到16个放松管制的类别，其中发育、受体活性和胞外区域代表了最大的类别。从IPA网络分析中鉴定出14个HUB基因(CEBPA、CEBPB、CTNNB1、FN1、MYC、MYCN、PLAU、SDC4、SERPINE1、SP1、TAF4B、THBS1、TP53和VLDLR)。对排序最高的网络(FN1、SERPINE1、THBS1和VLDLR)中的HUB基因进一步在29个细胞系的完整小组中进行qPCR分析。在这些基因中，FN1的高表达与高内在放射敏感性有关(p=0.047)。这些结果表明，FN1可以作为一种潜在的辐射抗性的新的生物标志物。
Radiotherapy remains the backbone of head and neck cancer therapy but response is sometimes impeded by tumor radioresistance. Identifying predictive biomarkers of radiotherapy response is a crucial step towards personalized therapy. The aim of this study was to explore gene expression data in search of biomarkers predictive of the response to radiotherapy in head and neck squamous cell carcinoma (HNSCC).Microarray analysis was performed on five cell lines with various intrinsic radiosensitivity, selected from a panel of 29 HNSCC cell lines. The bioinformatics approach included Gene Ontology (GO) enrichment profiling and Ingenuity Pathway Analysis (IPA). The GO-analysis detected 16 deregulated categories from which development, receptor activity and extracellular region represented the largest groups. Fourteen hub genes (CEBPA, CEBPB, CTNNB1, FN1, MYC, MYCN, PLAU, SDC4, SERPINE1, SP1, TAF4B, THBS1, TP53 and VLDLR) were identified from the IPA network analysis. The hub genes in the highest ranked network, (FN1, SERPINE1, THBS1 and VLDLR) were further subjected to qPCR analysis in the complete panel of 29 cell lines. Of these genes, high FN1 expression associated to high intrinsic radiosensitivity (p = 0.047).In conclusion, gene ontologies and hub genes of importance for intrinsic radiosensitivity were defined. The overall results suggest that FN1 should be explored as a potential novel biomarker for radioresistance.