Microarray gene expression analysis for development prognostic factors for oral squamous cell carcinoma

口腔鳞状细胞癌发展预后因素的微阵列基因表达分析

• 批准号: 12671929
• 负责人: NAGATA Masaki
• 金额: $ 2.24万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671929/
• 关键词: Oral sauamous cell carcinoma; Microarray; Gene expression profiling; Prognosis in metastasis; Diagnosis; lmmunohistochemistry; MMP; uPA; 口腔癌; 診断法

We performed gene expression profiling with 500 of the cancer related genes to develop diagnostic system of oral squamous cell carcinoma (OSCC). To eliminate biases caused by difference between tumors or measurements, we selected increased arid decreased genes in all OSCC cases. Unchangeable decreases were observed in gene expression ratio of Retinoic acid receptor gamma, Keratin family genes, and some molecules of desmosomes components against normal oral mucosa. Regular increases were observed in extracellular matrix (ECM)-degrading enzymes such as MMPs, uPA; ECMs such as Tenascin C and Fibronectin 1; Chemokines or transcription factors, such as MIG, IP-10, STAT1, BIGH3, that were induced by growth factors. Results of a cluster analysis indicated the similarity in gene expression patterns between those genes. The expression profile of cancer related genes in OSCC tissues seemed to reflect loss of epithelial characteristics, activated tissue destruction and formation of the cancer str … More oma, and disturbed phases in signal transudation systems. Comparison between groups with or without the involvement of lymphnode metastasis revealed significantly increased expression of MMP-1, uPA, CD44, Integrin alpha 3 and Paxillin as well as decreased mRNA levels of CD9 and IGFBP2. To confirm the results of gene expression analysis, we preformed immunohistochemistry for the genes that were suggested to associate with metastatic behavior of OSCCs. MMP-1, MMP-3 and uPA were co-localized extensively in inflammatory cells, endotherial cells and ECM structure, but no localization was indicated in tumor cells. Prominent staining of those gene products were observed on eosinophilic, round shaped mononuclear cells that were associated with degrading of surrounding collagen fibers and capillary structures. These histological findings corroborate the co-regulated expression and cooperative function of those ECM-degrading enzymes that were expected in gene expression analyzes. Striking correlation was demonstrated between MMP-1 mRNA revel and lymph node metastasis (U=0, p=0.001). MMP-1 could be an independent and accurate prognostic factor of lymph node metastasis for OSCC. By identifying commonly regulated and characteristic clusters of coexpressed genes, and by compeering the gene expression data with the extensive clinical data, and then by using immunohistochemistry against a subset of significant genes, surgical specimens with diverse backgrounds can be made accessible to extract valuable genes without prior dissection into components of tumor tissue. Less

我们对500个肿瘤相关基因进行了基因表达谱分析，以建立口腔鳞状细胞癌（OSCC）的诊断系统。为了消除肿瘤或测量值之间的差异所造成的偏倚，我们在所有OSCC病例中选择了增加和减少的基因。与正常口腔粘膜相比，维甲酸受体γ、角蛋白家族基因和桥粒组分的一些分子的基因表达率观察到不变的降低。观察到细胞外基质（ECM）降解酶（如MMP、uPA）; ECM（如腱生蛋白C和纤连蛋白1）;趋化因子或转录因子（如TGF β、IP-10、STAT 1、BIGH 3）由生长因子诱导的规律性增加。聚类分析的结果表明，这些基因之间的基因表达模式的相似性。口腔鳞癌组织中癌相关基因的表达谱似乎反映了上皮特征的丧失、激活的组织破坏和癌细胞的形成。 ...更多信息 OMA和信号泄漏系统中的干扰相位。有淋巴结转移组与无淋巴结转移组比较，MMP-1、uPA、CD 44、Integrin α 3和Paxillin表达均显著升高，而CD 9和IGFBP 2 mRNA水平显著降低。为了证实基因表达分析的结果，我们对被认为与OSCC转移行为相关的基因进行了免疫组化。MMP-1、MMP-3和uPA在炎性细胞、内皮细胞和ECM结构中广泛共定位，但在肿瘤细胞中未发现定位。在与周围胶原纤维和毛细血管结构降解相关的嗜酸性圆形单核细胞上观察到这些基因产物的显著染色。这些组织学发现证实了预期在基因表达分析中的那些ECM降解酶的共调节表达和合作功能。MMP-1 mRNA表达与淋巴结转移呈显著相关（U=0，p=0.001）。MMP-1可作为判断口腔鳞癌淋巴结转移的一个独立、准确的指标。通过识别共同表达基因的共同调节和特征簇，并将基因表达数据与广泛的临床数据进行比较，然后通过对重要基因的子集使用免疫组织化学，可以获得具有不同背景的手术标本，以提取有价值的基因，而无需事先解剖肿瘤组织的成分。少

项目成果

星名秀行: "進行・再発頭頚部癌の温熱化学放射線療法-背景因子からみた治療成績-"頭頚部腫瘍181-186. 27(1). 181-186 (2001)

Hideyuki Hoshina：“晚期/复发性头颈癌的热化疗-从背景因素的角度来看治疗结果”Head and Neck Tumor 181-186 181-186 (2001)。

Hoshina, H.: "Thermochemoradiotherapy for advanced or recurrent head and neck cancer: Analysis of clinical results and background variables"Head and Neck Cancer. 27 (1). 181-186 (2001)

Hoshina, H.：“晚期或复发性头颈癌的热化疗放疗：临床结果和背景变量分析”头颈癌。

永田昌毅: "DNAマイクロアレイを用いた口腔腫瘍の診断"新潟歯学会誌. 31(1). 35-37 (2001)

Masaki Nagata：“使用 DNA 微阵列诊断口腔肿瘤”，《新泻牙科学会杂志》31(1) (2001)。

Katsuhiro Nagashima: "Effect of local hyperthermia on metastases in oral squamous cell carcinoma Macmillan India Ltd. India"Oral Oncology. 7. 610 (2001)

Katsuhiro Nagashima：“局部热疗对口腔鳞状细胞癌转移的影响麦克米伦印度有限公司印度”口腔肿瘤学。

Hoshina H: "Thermochemoradiotherapy for advanced or recurrent head and neck cancer : Analysis of clinical results and background variables. Advances in Hyperthermic Oncology 2001, pl27-131 Tanaka R. Ed."Koko-Do Niigata. 153 (2001)

Hoshina H：“晚期或复发性头颈癌的热化疗放疗：临床结果和背景变量分析。高热肿瘤学进展 2001 年，pl27-131 Tanaka R. Ed.”Koko-Do Niigata。