Identification of potential therapeutic targets in human head & neck squamous cell carcinoma.

Identification of potential therapeutic targets in human head & neck squamous cell carcinoma.
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DOI:
10.1186/1758-3284-1-27
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发表时间:
2009-07-14
期刊:
Head & neck oncology
影响因子:
--
通讯作者:
Puri RK
Puri RK
中科院分区:
其他
文献类型:
--
作者:
Han J;Kioi M;Chu WS;Kasperbauer JL;Strome SE;Puri RK

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头颈部鳞状细胞癌是一种侵袭性和复发性的恶性肿瘤。鉴定独特或过表达的细胞相关或细胞表面抗原对于HNSCC的癌症疫苗和靶向治疗的诊断和开发至关重要。我们使用高通量微阵列技术来寻找HNSCC的候选靶点。应用基因芯片技术对17例HNSCC肿瘤和3例正常扁桃体组织进行基因表达谱分析。进行QRT-PCR分析以验证微阵列结果。通过免疫组织化学技术在手术标本和组织芯片中对这五个候选基因进行进一步的表征。与正常组织相比,在HNSCC肿瘤中鉴定了总共192个具有统计学显著性p < 0.01和log 2比率≥ 1的上调基因。这些基因属于免疫应答、细胞生长、细胞周期调控、癌基因、代谢等。鉴定了5个潜在的新靶基因(FABP 5、CD 24、CD 44、CD 74和HSP 27),它们在HNSCC肿瘤样品和组织阵列中高度表达。CD 24、CD 44和CD 74蛋白表达于细胞表面,FABP 5和HSP 27蛋白主要表达于细胞质。5个基因及其产物可能作为HNSCC的诊断标志物或治疗靶点。虽然需要额外的工作来阐明这些蛋白质的生物学意义,但CD 24和CD 74仅在小比例的细胞中表达,表明HNSCC中存在肿瘤异质性和肿瘤起始细胞的亚型(CD 24 +/CD 44+)。
Human head and neck squamous cell carcinoma (HNSCC) is an aggressive and recurrent malignancy. Identification of unique or overexpressed cell-associated or cell surface antigens is critical for diagnosis and development of cancer vaccines and targeted therapies for HNSCC. We have used high throughput microarray technology to search for candidate targets in HNSCC. Gene expression profiling in 17 HNSCC tumors and 3 normal tonsil tissues was performed by microarray. QRT-PCR analysis was performed to validate the microarray results. The five candidate genes were further characterized by immunohistochemical technique in surgical samples and tissue arrays. A total of 192 up-regulated genes at statistical significance of p < 0.01 and log2 ratio ≥ 1 were identified in HNSCC tumors compared to normal tissues. These genes belong to immune response, cell growth, cell cycle regulation, oncogenes, metabolism and others. Five potential novel target genes (FABP5, CD24, CD44, CD74, and HSP27) were identified, which were highly expressed in HNSCC tumor samples and tissue arrays. CD24, CD44, and CD74 proteins were expressed on the cell surface, and FABP5 and HSP27 proteins were predominantly expressed in the cytoplasm of HNSCC. Five genes and their products may serve as a diagnostic biomarker or therapeutic target for HNSCC. While additional work is needed to elucidate the biological significance of these proteins, CD24 and CD74 expressed only in small proportion of cells indicating tumor heterogeneity and subtypes of tumor initiating cells (CD24+/CD44+) present in HNSCC.
CD24是非小细胞肺癌患者中生存的独立预后标记。
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