Expression of ICAM-1, MMP-9 and NF-κB in Cholangiocarcinoma and Their Relationship with Immunosuppressive Cells in Peripheral Blood
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摘要:
目的 探讨细胞间粘附分子-1（ICAM-1）、基质金属蛋白酶-9（MMP-9）及NF-κB在胆管癌中的表达及外周血中CD14+CD11b+HAL-DR-髓源性抑制细胞（MDSC）的关系。 方法 选取昆明医科大学附属甘美医院2017年12月至2019年12月收治的胆管癌患者60例研究对象。采用免疫组化法测定胆管癌组织与癌旁正常组织ICAM-1蛋白、MMP-9蛋白及NF-κB蛋白；采用流式细胞术检测患者外周血中CD14+CD11b+HAL-DR-MDSC比例。比较胆管癌组织与癌旁组织ICAM-1蛋白、MMP-9蛋白和NF-κB蛋白表达；不同病理特征ICAM-1蛋白、MMP-9蛋白和NF-κB蛋白表达及外周血中CD14+CD11b+HAL-DR-MDSC比例；ICAM-1蛋白、MMP-9蛋白和NF-κB蛋白表达与外周血中CD14+CD11b+HAL-DR-MDSC比例相关性。 结果 胆管癌组织ICAM-1蛋白、MMP-9蛋白和NF-κB蛋白表达阳性率均高于癌旁正常组（P < 0.05）。不同性别、年龄、病理分级和淋巴结转移ICAM-1蛋白表达比较无明显差异（ P > 0.05）；III～IV期ICAM-1蛋白表达阳性率高于I～II期（ P < 0.05）。不同性别、年龄、病理分级和临床分期MMP-9蛋白表达比较无明显差异（ P > 0.05）；淋巴结转移MMP-9蛋白表达阳性率高于无淋巴结转移（ P < 0.05）。不同性别、年龄、病理分级和淋巴结转移NF-κB蛋白表达比较无明显差异（ P > 0.05）；III～IV期NF-κB蛋白表达阳性率高于I～II期（ P < 0.05）。不同性别、年龄、病理分级和淋巴结转移CD14 +CD11b+HAL-DR-MDSC比例比较无明显差异（P > 0.05）；III～IV期CD14 +CD11b+HAL-DR-MDSC比例高于I～II期（P < 0.05）。ICAM-1蛋白、MMP-9蛋白及NF-κB蛋白表达与CD14 +CD11b+HAL-DR-MDSC比例呈线性正相关。 结论 ICAM-1蛋白、MMP-9蛋白及NF-κB蛋白表在胆管癌中高表达，外周血中CD14+CD11b+HAL-DR-MDSC比例升高，且ICAM-1蛋白、MMP-9蛋白及NF-κB蛋白表达与CD14+CD11b+HAL-DR-MDSC比例呈线性正相关。 -
关键词:
- 细胞间粘附分子-1 /
- 基质金属蛋白酶-9 /
- NF-κB /
- 胆管癌 /
- CD14+CD11b+HAL-DR−髓源性抑制细胞
Abstract:Objective To investigate the expression of intercellular adhesion molecule-1 （ICAM-1）, matrix metalloproteinase-9(MMP-9） and NF-κB in cholangiocarcinoma and the relationship between CD14+CD11b+HAL-DR-MDSC in peripheral blood. Methods From December 2018 to December 2019, 60 patients with cholangiocarcinoma were selected. Immunohistochemistry was used to detect ICAM-1 protein, MMP-9 protein and NF-κB protein in cholangiocarcinoma and adjacent normal tissues, and flow cytometry was used to detect the ratio of CD14+CD11b+HAL-DR-MDSC in patients’peripheral blood. The expression of ICAM-1 protein, MMP-9 protein and NF-κB protein in cholangiocarcinoma and adjacent tissues were compared; the expression of ICAM-1 protein, MMP-9 protein and NF-κB protein in different pathological features and the ratio of CD14+CD11b+HAL-DR-MDSC in peripheral blood were compared; the expression of ICAM-1 protein, MMP-9 protein and NF-κB protein was correlated with the ratio of CD14+CD11b+HAL-DR-MDSC in peripheral blood. Results The positive rates of ICAM-1 protein, MMP-9 protein and NF-κB protein in cholangiocarcinoma were higher than those in normal group （P < 0.05）. There was no significant difference in the expression of ICAM-1 protein in different gender, age, pathological grade and lymph node metastasis （ P > 0.05）; the positive rate of ICAM-1 protein expression in stage III-IV was higher than that in stage I-II （ P < 0.05）. There was no significant difference in the expression of MMP-9 between different genders, ages, pathological grades and clinical stages （ P > 0.05）; the positive rate of MMP-9 in lymph node metastasis was higher than that in non lymph node metastasis （ P < 0.05）. There was no significant difference in the expression of NF-κB protein between different genders, ages, pathological grades and lymph node metastasis （ P > 0.05）; the positive rate of NF-κB protein expression in stage III-IV was higher than that in stage I-II （ P < 0.05）. There was no significant difference in the proportion of CD14 +CD11b+HAL-DR-MDSC in different sex, age, pathological grade and lymph node metastasis （P > 0.05）; the proportion of CD14 +CD11b+HAL-DR-MDSC in stage III-IV was higher than that in stage I-II （P < 0.05）. The expression of ICAM-1, MMP-9 and NF-κB was positively correlated with the ratio of CD14 +CD11b+HAL-DR-MDSC. Conclusion ICAM-1 protein, MMP-9 protein and NF-κB protein are highly expressed in cholangiocarcinoma, the ratio of CD14+CD11b+HAL-DR-MDSC in peripheral blood is increased, and the expression of ICAM-1 protein, MMP-9 protein and NF-κB protein is positively correlated with the ratio of CD14+CD11b+HAL-DR-MDSC. -
表 1 胆管癌组织与癌旁正常组织ICAM-1蛋白、MMP-9蛋白和NF-κB蛋白表达比较[n（%）]
Table 1. Comparison of ICAM-1 protein, MMP-9 protein and NF- κ B protein expression between cholangiocarcinoma and adjacent normal tissues [n（%）]
组别 n ICAM-1蛋白阳性率 MMP-9蛋白阳性率 NF-κB蛋白阳性率 胆管癌组织 60 41（68.33） 38（63.33） 47（78.33） 癌旁正常组织 60 11（18.33） 6（10.00） 8（13.33） χ2 - 30.543 36.746 51.054 P - < 0.001* < 0.001* < 0.001* *P< 0.05。 
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表 2 不同病理特征ICAM-1蛋白、MMP-9蛋白、NF-κB蛋白以及CD14+CD11b+HAL-DR-MDSC表达比较[n（%）]
Table 2. Comparison of ICAM-1 protein MMP-9 protein NF-κB protein and NF-κB protein expression in different pathological features [n（%）]
病理特征（例） ICAM-1
蛋白阳性χ2/P MMP-9
蛋白阳性χ2/P NF-κB
蛋白阳性χ2/P CD14+CD11b+HAL-DR−
MDSC比例（%）t/P 性别 男性（38） 28（73.68） 1.371/0.242 24（63.16） 0.001/0.970 32（84.21） 1.271/0.260 3.19 ± 0.92 0.243/0.809 女性（22） 13（59.09） 14（63.64） 15（68.18） 3.10 ± 0.95 年龄 > 60岁（26） 19（73.08） 0.447/0.490 19（73.08） 1.876/0.171 21（80.77） 0.160/0.689 3.23 ± 0.98 0.739/0.463 ≤60岁（34） 22（64.71） 19（55.88） 26（76.47） 3.05 ± 0.90 临床分期 I～II期（19） 6（31.58） 17.358/< 0.001* 9（47.37） 3.052/0.081 9（47.37） 13.152/< 0.001* 2.32 ± 0.83 6.069/< 0.001* III～IV期（41） 35（83.37） 29（70.73） 38（92.68） 3.97 ± 1.04 病理分级 低分化（34） 26（76.47） 2.401/0.121 23（67.65） 0.629/0.428 24（70.59） 2.773/0.096 3.20 ± 0.89 0.488/0.627 中高分化（26） 15（57.69） 15（57.69） 23（88.46） 3.08 ± 1.01 淋巴结转移 有（21） 15（71.43） 0.143/0.705 15（71.43） 7.959/0.005* 15（71.43） 0.390/0.533 3.28 ± 1.02 1.590/0.117 无（39） 26（66.67） 13（33.33） 32（82.05） 2.89 ± 0.84 *P < 0.05。
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表 3 ICAM-1蛋白、MMP-9蛋白及NF-κB蛋白表达与CD14+CD11b+HAL-DR-MDSC比例相关性
Table 3. Expression of ICAM-1 protein, MMP-9 protein and NF- κB protein and its correlation with the proportion of CD14 + CD11b + HAL-DR-MDSC
蛋白 CD14+CD11b+HAL-DR-MDSC比例 r P ICAM-1蛋白 0.819 <0.001* MMP-9蛋白 0.528 0.010* NF-κB蛋白 0.736 0.002* *P< 0.05。
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