肺癌CT全瘤灌注参数与基质金属蛋白酶-9缺氧诱导因子-1α表达的相关研究

The relationship between parameters of CT tumor perfusion and MMP-9/HIF-1α gene expression in lung cancer

目的探讨肺肿瘤CT全瘤灌注参数与肿瘤血管生成因子基质金属蛋白酶-9(MMP-9)及缺氧诱导因子-1α(HIF-1α)表达量的相关性,为肺癌的诊疗提供更多的帮助。方法对61例肺内单发≥2 cm的肿块性病变进行前瞻性CT全瘤灌注成像(CTPI),经后处理得出血流量(BF)、血容积(BV)、平均通过时间(MTT)、透析度(PMB)4个灌注参数;对手术或活检病理证实为肺癌的27例病灶进行免疫组织化学分析,对MMP-9及HIF-1α的表达进行半定量分析,并分别与CT灌注参数进行相关研究。统计学方法采用Spearman等级相关分析法。结果 27例肺癌BF平均值为(69±31)ml/(100 ml·min),BV平均值为(8±3)ml/(100 ml),MTT平均值为(8.6±2.0)s,PMB平均值为(15±6)ml/(100 ml·min)。MMP-9:阴性(-)4例,占15%;弱阳性(+)15例,占56%;中度阳性(++)8例,占30%;强阳性(+++)0例;总阳性率85%。HIF-1α:阴性(-)10例,占37%;弱阳性(+)12例,占44%;中度阳性(++)5例,占18%;强阳性(+++)0例;总阳性率63%。病灶BF、BV、PMB与MMP-9有相关性,呈正相关(r值分别0.391、0.611、0.700,P值均<0.05),MTT与MMP-9差异无统计学意义(r值为0.290,P值>0.05);BF与HIF-1α差异有统计学意义(r=0.454,P值<0.05),BV、MTT、PMB与HIF-1α差异无统计学意义(r值分别0.067、0.528、0.285,P值均>0.05)。结论 CT全瘤灌注参数与MMP-9、HIF-1α表达有一定相关性,可为临床对肺癌的个体化治疗提供一定的辅助信息。

Objective To investigate the correlation between lung tumors＇ CT tumor perfusion parameters and the relative expressions of MMP-9 and HIF-1α, thus provided further references for the diagnosis and treatment of lung cancer. Methods First of all, 61 recently diagnosed samples of pulmonary masses （lesions〉 2 cm） were prospectively undergone CT perfusion imaging （CTPI）. Then through the after-processing program of Siemens CT, four perfusion parameters were calculated： blood flow （BF）, blood volume （BV）, mean transit time （MTT）, and permeability （PMB）. Second, among these 61 cases, 27 cases of lung cancer confirmed by surgeries or biopsy specimens were sam- pled to undergo the EnvisionTM two-step immunohistochemical staining and the semi-quantitative analysis of their ex- pressions of MMP-9 and HIF-1α, then the data were respectively compared with the four previously defined CT perfu- sion parameters （including BF, BV, MTr and PMB）. Spearman ranking correlational analysis was adopted as the sta- tistical methodology. Results Of 27 cases of lung cancer, their mean value of BF is （69±31） ml/（100 ml. min）, BV （8±3） ml/100 ml, MTT （8.6±2.0） s, and PMB （15±6） ml/（100 ml.min）. MMP-9： negative （-） in 4 cases, accounting for 15%; weak positive （＋） in 15 cases, accounting for 56%; moderately positive （＋＋） in 8 cases, accounting for 30%; strong positive （＋＋＋） in 0 case. The total positive rate is 85%. HIF-1α： negative （-） in 10 cases, accounting for 37%; weak positive （＋） in 12 cases, accounting for 44%; moderately positive （＋＋） in 5 cases, accounting for 18%; strong positive （＋＋＋） in 0 case. The total positive rate is 63%. There is a positive correlation between BF, BV, PMB and MMP-9 （r=0.391, 0.611, 0.700; P〈0.05）. There is no statistical significance of the differences between MTT and MMP- 9 （r=0.290; P〉0.05）. There is statistical significance of the differerlces between BF and HIF-1α （r=0.454; P〈0.05）. There is no statistical significance of the differences between BV, MTT, PMB and HIF-1α （r values were 0.067, 0.528 and 0.285, respectively; P〉0.05）. Conclusion There is a moderate correlation between the CT perfusion parameters and the expressions of MMP-9 and HIF-1α, which can provide assistant information for the individual treatment of lung cancer.