Caveolin-1在喉鳞状细胞癌中的表达及其与肿瘤血管生成的相关研究

发布时间：2018-04-04 04:40

本文选题：喉癌　切入点：肿瘤血管生成　出处：《山西医科大学》2011年硕士论文

【摘要】：目的探讨caveolin-1和VEGF在喉癌组织中表达水平与两者在喉癌肿瘤血管生成中作用、相互关系及临床意义。对象标本源自山西医科大学第一临床附属医院耳鼻喉科2008年8月到2010年9月40例喉鳞癌标本，其中20例不伴颈淋巴结转移喉癌标本，20例伴有颈淋巴结转移喉癌标本，记录每位患者的详细临床资料，正常对照是8例正常喉粘膜组织。方法 1.选取40例喉癌组织及8例正常喉粘膜组织，应用caveolin-1抗体、CD34单克隆抗体及VEGF单克隆抗体，采用免疫组织化学技术检查caveolin-1、CD34、VEGF蛋白的表达。 2.选取40例喉癌组织及8例正常喉粘膜组织，用逆转录PCR(RT-PCR)法研究caveolin-1mRNA和VEGFmRNA的表达。结果 1．Caveolin-1蛋白主要表达于细胞胞膜和胞浆中，血管内皮也可见表达，正常组织阳性率75.0%，不伴有颈淋巴结转移的喉癌组阳性率25.0%，伴有颈淋巴结转移的喉癌组为65.0%，caveolin-1mRNA相对灰度值分别为0.701±0.073，0.350±0.050和0.572±0.061，，不论从基因水平还是蛋白水平三组之间差异有统计学意义（P＜0.05），两两比较亦均有显著性差异（P＜0.05），伴有颈淋巴结转移的喉癌组caveolin-1表达明显高于不伴有颈淋巴结转移的喉癌组（P㩳0.05），caveolin-1表达与颈淋巴转移呈显著相关。 2．VEGF表达于肿瘤细胞的胞浆中，正常组织阳性率25%，不伴有颈淋巴结转移的喉癌组阳性率55%，伴有颈淋巴结转移的喉癌组为75%，VEGFmRNA相对灰度值分别为0.614±0.321、0.801±0.473和1.413±0.586，不论从基因水平还是蛋白水平三组之间差异有统计学意义（P＜0.05），两两比较亦均有显著性差异（P＜0.05），伴有颈淋巴结转移的喉癌组VEGF表达明显高于不伴有颈淋巴结转移的喉癌组（P＜0.05），VEGF表达与颈淋巴转移呈显著相关。 3．正常组织、不伴有颈淋巴结转移的喉癌组和伴有颈淋巴结转移的喉癌组内CD34标记MVD分别为3.42±1.15、21.34±4.62和30.19±2.60，三组之间差异有统计学意义（P＜0.05），两两比较亦均有显著性差异（P＜0.05）。MVD与VEGF之间呈明显正相关（r=0.635，P0.01），40例喉癌组织中MVD与caveolin-1之间呈明显相关（r=0.424，P0.05）。 4．从蛋白和基因水平，正常组和不伴有颈淋巴结转移的喉癌组之间caveolin-1与VEGF表达呈负相关（P＜0.05），不伴有颈淋巴结转移的喉癌组和伴有颈淋巴结转移的喉癌组之间caveolin-1与VEGF表达呈正相关（P＜0.05）。结论喉癌细胞可以合成、分泌大量VEGF，其在肿瘤血管生成中起促进作用，肿瘤微血管密度是评价肿瘤血管生成的重要指标。研究显示caveolin-1在正常喉组织中表达较高，正常组织转化为喉癌时表达降低，并与微血管密度成负相关，提示caveolin-1抑制肿瘤血管的生成，其机制可能与抑制VEGF表达相关；caveolin-1在伴颈淋巴转移喉癌组织中表达水平较无颈淋巴转移喉癌组织高，且与微血管密度呈正相关，提示caveolin-1促进肿瘤血管生成，其机制可能与caveolin-1变异或促进VEGF表达相关，进而促进肿瘤侵袭和转移。
[Abstract]:objective
To investigate the expression level of caveolin-1 and VEGF in laryngeal carcinoma and their role in the angiogenesis of laryngeal cancer, and the relationship and clinical significance.
The object samples from the first clinical hospital of Shanxi Medical University from August 2008 to September 2010 in Department of ENT, 40 cases of laryngeal squamous cell carcinoma, 20 cases with cervical lymph node metastasis in laryngeal carcinoma, 20 cases with cervical lymph node metastasis in laryngeal carcinoma, record the detailed clinical data of each patient, the control is 8 cases of normal laryngeal mucosa.
Method
1. 40 cases of laryngeal carcinoma and 8 cases of normal laryngeal mucosa tissues were selected. The expression of caveolin-1, CD34 and VEGF protein was detected by immunohistochemistry, using caveolin-1 antibody, CD34 monoclonal antibody and VEGF monoclonal antibody.
2. the expression of caveolin-1mRNA and VEGFmRNA in 40 cases of laryngeal carcinoma and 8 cases of normal laryngeal mucosa were studied by reverse transcriptase PCR (RT-PCR).
Result
1.Caveolin-1 protein was mainly expressed in the cell membrane and in cytoplasm of vascular endothelial expression of normal tissue is also visible, the positive rate was 75%, without cervical lymph node metastasis in laryngeal carcinoma group, the positive rate was 25%, with cervical lymph node metastasis in laryngeal carcinoma group was 65%, caveolin-1mRNA relative gray value of 0.701 + 0.073,0.350 + 0.050 and 0.572 + 0.061, there was statistical significance from the gene level and protein level differences between the three groups (P < 0.05), 22 were also significantly different (P < 0.05), with lymph node metastasis in laryngeal carcinoma group caveolin-1 expression was significantly higher than without lymph node metastasis in laryngeal carcinoma group (P? 0.05), caveolin-1 the expression was significantly correlated with lymph node metastasis.
2.VEGF expressed in cytoplasm of tumor cells in normal tissues, the positive rate was 25%, without cervical lymph node metastasis in laryngeal carcinoma group, the positive rate was 55%, with cervical lymph node metastasis in laryngeal carcinoma group was 75%, the relative gray scale values of VEGFmRNA were 0.614 + 0.321,0.801 + 0.473 and 1.413 + 0.586, no matter from the gene level or protein level between the three groups was statistically significant (P < 0.05), 22 were also significantly different (P < 0.05), the expression was significantly higher than that associated with cervical lymph node metastasis in laryngeal carcinoma group VEGF laryngeal carcinoma group with the cervical lymph node metastasis (P < 0.05), the expression of VEGF was significantly correlated with lymph node metastasis.
3. normal tissues, without cervical lymph node metastasis in laryngeal carcinoma group with cervical lymph node metastasis in laryngeal carcinoma group CD34 labeled MVD were 3.42 + 1.15,21.34 + 4.62 and 30.19 + 2.60, there were statistically significant differences between the three groups (P < 0.05), 22 were also significantly different (P < 0.05) is a significant positive correlation between.MVD and VEGF (r=0.635, P0.01), showed a significant correlation between MVD and caveolin-1 in 40 cases of laryngeal carcinoma tissues (r=0.424, P0.05).
4. from the level of gene and protein, the normal group and the group without metastasis of laryngeal carcinoma between caveolin-1 and VEGF expression was negatively related to cervical lymph node (P < 0.05), not associated with cervical lymph node metastasis in laryngeal carcinoma group with cervical lymph node metastasis in laryngeal carcinoma group between caveolin-1 and VEGF expression of Cheng Zhengxiang (P < 0.05).
conclusion
Laryngeal cancer cells can synthesis and secretion of VEGF, which play an important role in tumor angiogenesis, tumor microvessel density is an important index for evaluation of tumor angiogenesis. Research shows that high levels of caveolin-1 in normal laryngeal tissues, normal tissue into laryngeal carcinoma expression and microvessel density decreased, and a negative correlation that generate caveolin-1 inhibition of tumor angiogenesis and its mechanism may be related to the inhibition of VEGF expression; caveolin-1 with cervical lymph node metastasis in laryngeal carcinoma tissue expression was no lymph node metastasis in laryngeal carcinoma is high, and the correlation with microvessel density positively, suggesting that caveolin-1 promote tumor angiogenesis, and its mechanism may be related to caveolin-1 mutation or promote the expression of VEGF, and promote the invasion and metastasis of tumor.

【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R739.65

【参考文献】