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目的探讨细胞外间质韧黏素-C(TN-C)的分解与非小细胞肺癌(NSCLC)术后复发的关系,以及TN-C分解的分子机制。方法收集63例Ⅰ期NSCLC患者的组织标本,以Western blot测定TN-C蛋白的表达,明胶酶谱法测定基质金属蛋白酶(MMPs)的活性。结果63例患者中,12例检测到TN-C的分解片段。有TN-C分解组肺癌组织与正常肺组织MMP-2活性之比为3.5±0.4,明显高于无TN-C分解组(1.5±0.4,P<0.001)。有无TN-C分解与肺癌的复发、转移有关,可检测到小分子TN-C片段者复发、转移率高(P<0.001)。无TN-C分解患者的5年生存率为73.9%,高于有TN-C分解的患者(45.8%,P=0.028)。无TN-C分解患者的4年和10年无复发生存率分别为82.1%和76.6%,高于有TN-C分解的患者(P<0.001)。结论TN-C分解片段是NSCLC术后复发、转移的有效指标,MMP-2可能是肺癌组织中分解TN-C的重要蛋白酶。
Objective To investigate the relationship between the degradation of extracellular matrix tenosyn-C (TN-C) and the recurrence of non-small cell lung cancer (NSCLC) and the molecular mechanism of TN-C degradation. Methods Tissue samples of 63 patients with stage Ⅰ NSCLC were collected. The expression of TN-C protein was detected by Western blot and the activity of matrix metalloproteinases (MMPs) by gelatin zymography. Results Of 63 patients, TN-C fragments were detected in 12 cases. The ratio of MMP-2 activity in lung cancer tissue to normal lung tissue in TN-C group was 3.5 ± 0.4, which was significantly higher than that in non-TN-C group (1.5 ± 0.4, P <0.001). The presence or absence of TN-C degradation is associated with the recurrence and metastasis of lung cancer, which can detect small molecule TN-C fragments recurrence and metastasis rate (P <0.001). The 5-year survival rate of patients without TN-C was 73.9%, higher than those with TN-C (45.8%, P = 0.028). The 4-year and 10-year non-recurrence-free survival rates for patients without TN-C were 82.1% and 76.6%, respectively, higher than those with TN-C breakdown (P <0.001). Conclusion The TN-C fragment is an effective indicator of the recurrence and metastasis of NSCLC. MMP-2 may be an important protease that decomposes TN-C in lung cancer.