人白细胞介素24表达水平与食管癌进程相关性的研究

发布时间：2018-06-05 11:40

  本文选题：IL-24 + 食管癌　； 参考：《北京交通大学》2017年硕士论文

【摘要】：目的:人白细胞介素24(interleukin 24,IL-24)能够在体内外特异性抑制多种肿瘤细胞增殖,诱导其凋亡,对正常细胞没有影响;同时,可以抑制新生血管形成,刺激免疫系统对肿瘤发生反应,增加肿瘤细胞的放化疗敏感性;并且,随着黑色素瘤发生和发展,IL-24的表达水平显著降低,肿瘤患者(肺腺癌、乳腺癌和结肠癌)癌组织中IL-24表达水平高则预后良好,提示IL-24可能是一个新的肿瘤预后标志物。为了明确IL-24表达水平与食管癌进程相关性,本文测定和分析了食管癌患者组织标本和血液标本中IL-24表达水平。方法:采用免疫组织化学(Immunohistochemical,IHC)方法检测84位食管癌患者配对标本(肿瘤组织,癌旁组织和正常组织)中IL-24表达水平,以及与IL-24 作用机制相关分子(如细胞增殖、细胞凋亡、细胞周期、新生血管形成、化疗增敏、原癌基因、肿瘤干细胞、上皮间质转换、细胞自噬等)的表达水平。同时用酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA)方法检测了1940例血液标本中的IL-24、人白细胞介素6(interleukin 6,IL-6)、人白细胞介素10(interleukin 10,IL-10)和肿瘤坏死因子 α(tumornecrosis factor α,TNF-α)的含量;以及13例食管癌患者血液标本中IL-24的含量。结果:(1)在食管癌配对的组织标本中IL-24表达水平存在差异,其中肿瘤组织中最高,正常组织中最低;(2)IL-24表达水平与84例食管癌患者年龄、性别、组织类型、病变部位、病理分级、肿瘤分期(肿瘤大小和淋巴结转移)和43例食管癌的分化程度等临床特征,无统计学意义的相关性,但与69例食管鳞癌的肿瘤大小(p=0.09)和淋巴结转移(p=0.06)负相关;(3)食管癌的癌组织中IL-24表达水平与凋亡标志分子半胱氨酸的天冬氨酸蛋白水解酶3(cysteinyl aspartate specific proteinase 3,Caspase3)正相关,与 Fas 和 DNA 错配修复标志分子 hMLH1(MutL homolog 1)负相关,具有统计学意义。(4)血液标本处理方式影响IL-24的检测结果,同一位献血者EDTA抗凝血中IL-24的检出值最高,柠檬酸钠抗凝血的最低。血液标本在4℃存放15天对IL-24检测结果影响不明显。(5)血清中IL-24浓度与献血者的年龄和血液生化指标(血糖、血红蛋白、总胆固醇、癌胚抗原、淋巴细胞绝对值、甲胎蛋白、白细胞、促甲状腺激素、谷丙转氨酶等)无关。(6)血液中IL-24表达水平与致炎因子IL-6和TNF-α表达水平正相关,与抗炎因子IL-10表达水平负相关,p值均小于0.05,具有统计学意义。结论:食管癌组织中IL-24蛋白表达水平远高于配对的癌旁组织和正常组织,且IL-24表达水平与食管鳞癌的肿瘤大小和淋巴结转移数量负相关,提示IL-24可能在食管鳞癌的发展进程中发挥作用。
[Abstract]:Objective: human interleukin (24(interleukin) 24 IL-24 can specifically inhibit the proliferation of many tumor cells in vitro and in vivo, induce their apoptosis, and have no effect on normal cells, at the same time, they can inhibit angiogenesis and stimulate the immune system to respond to tumor. The expression of IL-24 was significantly decreased with the development of melanoma, and the higher expression of IL-24 in cancer tissues (lung adenocarcinoma, breast cancer and colon cancer) had a good prognosis. The results suggest that IL-24 may be a new prognostic marker. In order to determine the correlation between the expression of IL-24 and the progression of esophageal cancer, the expression of IL-24 in tissues and blood samples of patients with esophageal cancer was measured and analyzed. Methods: immunohistochemical method was used to detect the expression of IL-24 in 84 matched specimens of esophageal carcinoma (tumor tissues, adjacent tissues and normal tissues), as well as the molecules related to the mechanism of IL-24, such as cell proliferation and apoptosis. Cell cycle, neovascularization, chemosensitization, proto-oncogene, tumor stem cells, epithelial mesenchymal transformation, autophagy, etc. The contents of IL-24, IL-6, IL-6, IL-10 and TNF- 伪 in 1940 blood samples were also detected by enzyme linked immunosorbent assayanine Elisa. The levels of IL-24, IL-6, IL-10 and TNF- 伪) in 1940 blood samples were determined by Elisa. The serum levels of IL-24, IL-6, IL-10 and TNF- 伪 in 1940 blood samples were determined by Elisa. And the content of IL-24 in blood of 13 patients with esophageal carcinoma. Results there was significant difference in the expression of IL-24 in the matched tissues of esophageal carcinoma. The expression level of IL-24 was the highest in the tumor tissue and the lowest in the normal tissue. The expression level of IL-24 was the same as the age, sex, type of tissue, pathological grade and pathological grade of 84 patients with esophageal carcinoma. The clinical features of tumor staging (tumor size and lymph node metastasis) and the differentiation of 43 cases of esophageal carcinoma were not correlated with statistical significance. However, the expression of IL-24 was negatively correlated with tumor size (p0.09) and lymph node metastasis (p0.06) in 69 cases of esophageal squamous cell carcinoma. The expression of IL-24 was positively correlated with the apoptotic marker cysteine aspartate protein hydrolase 3(cysteinyl aspartate specific proteinase 3 (caspase3). It was negatively correlated with Fas and DNA mismatch repair marker molecule hMLH1(MutL homolog 1, and had statistical significance. 4) the treatment of blood samples affected the detection results of IL-24. In the same blood donor, the detection value of IL-24 was the highest in EDTA and the lowest in sodium citrate anticoagulant. Blood samples stored at 4 鈩，

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