Expression and clinical significance of glutaminase and matrix metalloproteinase-2, 9 in prostate cancer tissue
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摘要: 目的 探讨谷氨酰胺酶(GLS1)、基质金属蛋白酶-2、9(MMP-2、MMP-9)在前列腺癌中的表达程度及表达相关性与前列腺癌疾病进展的关系。方法 收集40例前列腺癌组织与40例前列腺增生组织，行免疫组织化学染色检测组织中GLS1、MMP-2、MMP-9的表达，对2组间上述蛋白的表达差异进行分析，并将其表达程度与相应的前列腺癌组织的临床病理特征进行分析；比较上述蛋白表达的相关性与前列腺癌的相关性。统计学方法采用t检验、χ2检验、Spearman相关分析等。结果 前列腺癌组织中GLS1显著高于前列腺增生组织(χ2=65.777，P< 0.01)。前列腺癌组织中MMP-2显著高于前列腺增生组织(χ2=20.652，P< 0.01)。前列腺癌组织中MMP-9显著高于前列腺增生组织(χ2=51.551，P< 0.01)。MMP-2在分期为Ⅰ~Ⅱ、Ⅲ~Ⅳ期的前列腺癌组织的表达差异有统计学意义(χ2=4.862，P< 0.05)。MMP-9在分期为Ⅰ~Ⅱ、Ⅲ~Ⅳ期的前列腺癌组织的表达差异有统计学意义(χ2=8.379，P< 0.05)，在Gleason评分≤7分组和>7分组的组织中的表达差异有统计学意义(χ2=6.327，P< 0.05)。Spearman相关分析结果提示MMP-2与MMP-9在前列腺癌病理标本中的表达呈正相关(r=0.432，P< 0.01)，MMP-2与GLS1在前列腺癌病理标本中的表达呈正相关(r=0.410，P< 0.01)，MMP-9与GLS1在前列腺癌病理标本中的表达呈正相关(r=0.365，P< 0.05)，前列腺癌TNM分期与MMP-2(r=0.369，P< 0.05)、MMP-9(r=0.429，P< 0.01)的表达呈正相关。结论 前列腺癌组织中具有GLS1、MMP-2、MMP-9的高表达，且上述蛋白在前列腺癌细胞中的表达呈正相关。Abstract: Objective To investigate the expression of glutaminase(GLS1), matrix metalloproteinase-2(MMP-2), matrix metalloproteinase-9(MMP-9) in prostate cancer and the relationship between their expression and the progression of prostate cancer.Methods Forty cases of prostate cancer tissues and 40 cases of benign prostatic hyperplasia tissues were collected, and the expressions of GLS1, MMP-2 and MMP-9 in the tissues were detected by immunohistochemical staining. The degree of expression and the clinicopathological characteristics of the corresponding prostate cancer tissues were analyzed, and the correlation among the expression of several proteins and the correlation with prostate cancer were compared. Statistical methods includingttest, χ2test, Spearman correlation analysis and so on were used.Results GLS1 in prostate cancer tissue was significantly higher than that in benign prostatic hyperplasia tissue (χ2=65.777,P< 0.01). MMP-2 in prostate cancer tissue was significantly higher than that in benign prostatic hyperplasia tissue (χ2=20.652,P< 0.01). MMP-9 in prostate cancer tissue was significantly higher than that in benign prostatic hyperplasia (χ2=51.551,P< 0.01). There was significant difference in the expression of MMP-2 in prostate cancer tissues of stages Ⅰ-Ⅱ and Ⅲ-Ⅳ (χ2=4.862,P< 0.05). The expression difference of MMP-9 in prostate cancer tissues of stages Ⅰ-Ⅱ and Ⅲ-Ⅳ was statistically significant (χ2=8.379,P< 0.05), and the expression of MMP-9 in the tissues of Gleason score ≤7 group and >7 group was significantly different (χ2=6.327,P< 0.05). The results of Spearman correlation analysis showed that the expressions of MMP-2 and MMP-9 in prostate cancer pathological specimens were positively correlated (r=0.432,P< 0.01), and the expressions of MMP-2 and GLS1 in prostate cancer pathological specimens were positively correlated (r=0.410,P< 0.01). The expression of MMP-9 and GLS1 in prostate cancer pathological specimens were positively correlated (r=0.365,P< 0.05), and the TNM staging of prostate cancer was positively correlated with MMP-2 (r=0.369,P< 0.05) and MMP-9 (r=0.429,P< 0.01).Conclusion Prostate cancer tissue has high expression of GLS1, MMP-2, MMP-9, and the expression of several proteins in prostate cancer cells is positively correlated.
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Key words:
- prostate cancer /
- glutaminase /
- matrix metalloproteinase-2 /
- matrix metalloproteinase-9
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表 1 2组患者一般资料比较
项目 总体(n=80) 前列腺癌组(n=40) 前列腺增生组(n=40) t/Z P 年龄/岁 69.33±7.03 70.23±6.96 68.43±7.07 1.147 0.255 BMI 23.67±3.05 23.28±2.83 24.07±3.24 -1.160 0.249 体积/cm3 47.6(36.4，68.6) 41.85(35.18，63.75) 54.2(42.88，72.65) -2.314 0.021 
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表 2 MMP-2、MMP-9在前列腺癌和前列腺增生组织中的表达阳性率比较
例 组织学类型 例 GLS1 P MMP-2 P MMP-9 P - + ++ +++ - + ++ +++ - + ++ +++ 前列腺癌 40 0 11 8 21 < 0.001 13 3 9 15 < 0.001 0 17 16 7 < 0.001 前列腺增生 40 3 27 10 0 21 10 9 0 24 12 4 0
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表 3 MMP-2、MMP-9在前列腺癌中的表达与前列腺癌临床病理特征的关系
例 临床病理特征 例数 MMP-2 P MMP-9 P 阴性 阳性 阴性 弱阳性 阳性 强阳性 TNM分期 0.027 0.015 Ⅰ~Ⅱ 24 11 13 0 13 10 1 Ⅲ~Ⅳ 16 2 14 0 4 6 6 Gleason评分/分 0.091 0.042 ≤7 20 9 11 0 8 11 1 > 7 20 4 16 0 9 5 6 PSA/(ng·mL-1) 0.427 0.108 ≤20 21 8 13 0 12 7 2 > 20 19 5 14 0 5 9 5
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表 4 GLS1在前列腺癌中的表达与前列腺癌临床病理特征的关系
例 临床病理特征 例数 GLS P 阴性 弱阳性 阳性 强阳性 TNM分期 0.710 Ⅰ~Ⅱ 24 0 1 12 11 Ⅲ~Ⅳ 16 0 0 6 10 Gleason评分/分 0.205 ≤7 20 0 1 11 8 > 7 20 0 0 7 13 PSA/(ng·mL-1) 0.112 ≤20 21 0 1 12 8 > 20 19 0 0 6 13
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