肺癌支气管灌洗液MMP-7、Survivin mRNA的表达及临床意义
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摘要
目的
明确肺癌患者支气管灌洗液(bronchial lavage fluid, BLF)细胞基质金属蛋白酶-7(matrix metalloproteinase-7, MMP-7)、Survivin mRNA表达情况,及其表达水平与肺癌临床各因素、BLF方式之间的关系,探讨BLF细胞MMP7、Survivin mRNA表达情况作为肿瘤标志物在肺癌尤其是周围型肺癌早期诊断等方面的临床意义。
方法
采用RT-PCR(reverse polymerase chain reaction)方法,检测124例肺癌患者、103例支气管肺部良性疾病患者BLF细胞中MMP7 mRNA、Survivin mRNA的表达情况,以及42例肺癌及30例支气管肺部良性疾病患者支气管钳夹活检组织(forceps biopsy, FB)MMP7 mRNA、Survivin mRNA的表达情况,分析BLF细胞MMP-7 mRNA、Survivin mRNA在肺癌及非肺癌两组患者表达情况,BLF标本MMP-7 mRNA、Survivin mRNA表达与肺癌临床各因素、BLF方式之间的相关性,并与BLF病理细胞学等检查结果相比较,运用ROC分析系统,评价BLF中MMP-7 mRNA、Survivin mRNA表达在肺癌诊断尤其是周围型肺癌诊断方面的价值。
结果
1.检测MMP-7 mRNA、Survivin mRNA表达,FB与BLF两配对标本一致性较好(Kappa值分别为0.419、0.567,P值分别为0.001、0.000)。
2.肺癌组BLF标本Survivin mRNA阳性率45.2%(56/124)显著高于非肺癌组18.4%(19/103),差异有统计学意义(χ2=18.150、P=0.000),但BLF标本MMP7mRNA阳性率24.2%(30/124)与非肺癌组18.4%(19/103)之间差异无统计学意义(χ2=1.098,P=0.295)。
3.肺癌患者BLF标本Survivin mRNA相对表达量与肺癌病理类型(小细胞肺癌)、肺癌分化程度(低分化肺癌)及TNM分期(T分期)均有相关性(均P<0.05);BLF标本MMP-7 mRNA相对表达量与抽烟史有明显相关性(P<0.05)。
4.肺癌患者BLF标本Survivin mRNA阳性率43.4%(49/113)、Survivin mRNA联合MMP-7 mRNA阳性率51.3%(58/113)均显著高于BLF标本病理细胞学阳性率23.9%(27/113),差异均有统计学意义(χ2值分别为9.595、18.121,P值分别为0.002、0.000);BLF标本病理细胞学阳性率23.9%(27/113)与BLF标本MMP-7 mRNA阳性率22.1%(25/113)比较,差异无统计学意义(χ2=0.100、P=0.752);细胞病理学未检出癌细胞的86例肺癌患者BLF标本中,仍有21例(24.4%)MMP-7 mRNA、38例(44.2%)Survivin mRNA、51例(59.3%)MMP-7 mRNA或Survivin mRNA表达阳性。BLF标本病理细胞学检查联合MMP-7 mRNA、Survivin mRNA检测,可提高单独病理细胞学检查诊断肺癌阳性率。
5.检测BLF标本Survivin mRNA、MMP-7 mRNA表达诊断肺癌,敏感性分别为45.2%、24.2%,特异性分别为81.6%、81.6%,两标志物联合检测敏感性、特异性可分别提高为52.4%、97.1%;检测BLF标本Survivin mRNA、MMP-7 mRNA表达诊断周围型肺癌,敏感性分别为35.9%、23.1%,特异性分别为85.4%、85.4%;联合检测MMP-7 mRNA和Survivin mRNA诊断周围型肺癌的敏感性、特异性分别为43.6%、98.1%。
结论
本研究表明: 1.支气管灌洗液(BLF)标本Survivin mRNA诊断肺癌具有较高的敏感性、特异性,可能成为肺癌(尤其是周围型肺癌)早期诊断的分子肿瘤标志物之一;BLF标本MMP-7 mRNA诊断肺癌的敏感性较低、一致性不好,其诊断价值不大,仍需进一本观察研究。2. BLF标本Survivin mRNA、MMP-7 mRNA联合BLF标本病理细胞学,Survivin mRNA联合MMP-7 mRNA,可提高肺癌(尤其是周围型肺癌)诊断价值。3. BLF标本获取方式不影响Survivin mRNA、MMP-7 mRNA表达检测结果。
Objective
To study the expression of matrix metalloproteinase-7(MMP-7), survivin messenger RNA(mRNA) in specimen from bronchial lavage fluid(BLF) of lung cancer, and to study the correlation between expression of MMP-7, survivin and clinical features and different bronchial lavage sequences as well. To explore the clinical value of MMP-7 mRNA, survivin mRNA in BLF specimens as tumor makers for earlier diagnosis of lung cancer, especialy peripheral lung cancer.
Methods
Bronchial lavage fluid(BLF) were collected from 124 cases suffering from lung cancer, 103 cases suffering from pulmonary benign diseases. Forceps biopsy(FB) were collected from 42 cases suffering from lung cancer, 30 cases suffering from pulmonary benign diseases. All specimens were deteced the expression of MMP-7, survivin messenger RNA(mRNA) with the method of reverse polymerase chain reaction(RT-PCR). The expression of MMP-7 mRNA, survivin mRNA in patients with lung cancer and non-lung cancer, the correlation between expression of MMP-7 mRNA, survivin mRNA and clinical features, different bronchial lavage sequences were studied. The results were compared with their cytopathological examinations. The clinical value of MMP-7 mRNA, survivin mRNA in BLF specimens as specific tumor makers for earlier diagnosis, especialy peripheral lung cancer was evaluated by ROC (receiver operating characteristic curve) analytical system.
Results
1. To detect MMP-7 mRNA、survivin mRNA expression in patients with lung cancer and non-lung cancer the consistencies were better in paired specimens FB and BLF(Kappa=0.419, 0.567; P=0.001, 0.000).
2. The positive rate of survivin mRNA in specimen from BLF of lung cancer 45.2%(56/124) was higher than that 18.4%(19/103) in specimen from BLF of non-lung cancer, and there was significant difference between the positive rate of survivin mRNA in specimen from BLF of lung cancer and that in specimen from BLF of non-lung cancer(χ2=18.150, P=0.000), but there was no significant difference between the positive rate of MMP-7 mRNA in specimen from BLF of lung cancer 24.2%(30/124) and that 18.4%(19/103) in specimen from BLF of non-lung cancer(χ2=1.098, P=0.295).
3. There were correlation between survivin expression and histopathological subtype(small cell lung cancer), differentiation(lower differentiation), T of TNM stages(all P<0.05). There was correlation between MMP-7 mRNA expression and smoking(P<0.05).
4. There was no difference between the positive rate of cytopathological examination (23.9%) and that (22.1%) of MMP-7 mRNA (χ2=0.100、P=0.752), while there were significant difference between the positive rate of cytopathological examination and that (43.4%) of survivin mRNA, that (51.3%) MMP-7 mRNA combined with survivin mRNA from BLF specimens (χ2=9.595, 18.121; P=0.002, 0.000 ). The positive rates of MMP-7 mRNA, survivin mRNA and MMP-7 mRNA combined with survivin mRNA from BLF specimens were 24.2%(21/124), 44.2%(38/86), 59.3%(51/86) respectively, while the positive rate of cytopathological examinations from BLF specimens was zero. The sensitivity of cytological examinations combined with detecting MMP-7 mRNA, survivin mRNA from BLF specimens was higher than that of either cytological examination or MMP-7 mRNA, survivin mRNA detection of BLF specimens alone(all P<0.05).
5. The sensitivity and specificity of the diagnosis for lung cancer by detecting MMP-7 mRNA, survivin mRNA, MMP-7 mRNA combined with survivin mRNA in BLF specimens were respectively: 24.2%, 45.2%, 52.4% and 81.6%, 81.6%, 97.1%. The sensitivity and specificity of the diagnosis for peripheral lung cancer by detecting MMP-7 mRNA, survivin mRNA, MMP-7 mRNA combined with survivin mRNA from BLF specimens were respectively: 23.1%, 35.9%, 43.6% and 85.4%, 85.4%, 98.1%.
Conclusions
Conclusions drawn from this study are as following:
1. Expression of survivin mRNA in specimens from bronchial lavage fluid(BLF) might be used as the specific molecular markers for diagnosis of lung cancer especially peripheral lung cancer because of it,s higher sensitivity and specificity. The diagnosis value of expression of MMP-7 mRNA in specimens from BLF should be studied further for it’s lower sensitivity and poor consistency.
2. It can make the diagnosis sensitivity for lung cancer especialy peripheral lung cancer improved greatly that detecting cytological examination combined with survivin mRNA, or, and with MMP-7 mRNA, and that detecting survivin mRNA combined with MMP-7 mRNA.
3. The outcome of expression of MMP-7 mRNA, survivin mRNA don't be affected by the different bronchial lavage sequences.
明确肺癌患者支气管灌洗液(bronchial lavage fluid, BLF)细胞基质金属蛋白酶-7(matrix metalloproteinase-7, MMP-7)、Survivin mRNA表达情况,及其表达水平与肺癌临床各因素、BLF方式之间的关系,探讨BLF细胞MMP7、Survivin mRNA表达情况作为肿瘤标志物在肺癌尤其是周围型肺癌早期诊断等方面的临床意义。
方法
采用RT-PCR(reverse polymerase chain reaction)方法,检测124例肺癌患者、103例支气管肺部良性疾病患者BLF细胞中MMP7 mRNA、Survivin mRNA的表达情况,以及42例肺癌及30例支气管肺部良性疾病患者支气管钳夹活检组织(forceps biopsy, FB)MMP7 mRNA、Survivin mRNA的表达情况,分析BLF细胞MMP-7 mRNA、Survivin mRNA在肺癌及非肺癌两组患者表达情况,BLF标本MMP-7 mRNA、Survivin mRNA表达与肺癌临床各因素、BLF方式之间的相关性,并与BLF病理细胞学等检查结果相比较,运用ROC分析系统,评价BLF中MMP-7 mRNA、Survivin mRNA表达在肺癌诊断尤其是周围型肺癌诊断方面的价值。
结果
1.检测MMP-7 mRNA、Survivin mRNA表达,FB与BLF两配对标本一致性较好(Kappa值分别为0.419、0.567,P值分别为0.001、0.000)。
2.肺癌组BLF标本Survivin mRNA阳性率45.2%(56/124)显著高于非肺癌组18.4%(19/103),差异有统计学意义(χ2=18.150、P=0.000),但BLF标本MMP7mRNA阳性率24.2%(30/124)与非肺癌组18.4%(19/103)之间差异无统计学意义(χ2=1.098,P=0.295)。
3.肺癌患者BLF标本Survivin mRNA相对表达量与肺癌病理类型(小细胞肺癌)、肺癌分化程度(低分化肺癌)及TNM分期(T分期)均有相关性(均P<0.05);BLF标本MMP-7 mRNA相对表达量与抽烟史有明显相关性(P<0.05)。
4.肺癌患者BLF标本Survivin mRNA阳性率43.4%(49/113)、Survivin mRNA联合MMP-7 mRNA阳性率51.3%(58/113)均显著高于BLF标本病理细胞学阳性率23.9%(27/113),差异均有统计学意义(χ2值分别为9.595、18.121,P值分别为0.002、0.000);BLF标本病理细胞学阳性率23.9%(27/113)与BLF标本MMP-7 mRNA阳性率22.1%(25/113)比较,差异无统计学意义(χ2=0.100、P=0.752);细胞病理学未检出癌细胞的86例肺癌患者BLF标本中,仍有21例(24.4%)MMP-7 mRNA、38例(44.2%)Survivin mRNA、51例(59.3%)MMP-7 mRNA或Survivin mRNA表达阳性。BLF标本病理细胞学检查联合MMP-7 mRNA、Survivin mRNA检测,可提高单独病理细胞学检查诊断肺癌阳性率。
5.检测BLF标本Survivin mRNA、MMP-7 mRNA表达诊断肺癌,敏感性分别为45.2%、24.2%,特异性分别为81.6%、81.6%,两标志物联合检测敏感性、特异性可分别提高为52.4%、97.1%;检测BLF标本Survivin mRNA、MMP-7 mRNA表达诊断周围型肺癌,敏感性分别为35.9%、23.1%,特异性分别为85.4%、85.4%;联合检测MMP-7 mRNA和Survivin mRNA诊断周围型肺癌的敏感性、特异性分别为43.6%、98.1%。
结论
本研究表明: 1.支气管灌洗液(BLF)标本Survivin mRNA诊断肺癌具有较高的敏感性、特异性,可能成为肺癌(尤其是周围型肺癌)早期诊断的分子肿瘤标志物之一;BLF标本MMP-7 mRNA诊断肺癌的敏感性较低、一致性不好,其诊断价值不大,仍需进一本观察研究。2. BLF标本Survivin mRNA、MMP-7 mRNA联合BLF标本病理细胞学,Survivin mRNA联合MMP-7 mRNA,可提高肺癌(尤其是周围型肺癌)诊断价值。3. BLF标本获取方式不影响Survivin mRNA、MMP-7 mRNA表达检测结果。
Objective
To study the expression of matrix metalloproteinase-7(MMP-7), survivin messenger RNA(mRNA) in specimen from bronchial lavage fluid(BLF) of lung cancer, and to study the correlation between expression of MMP-7, survivin and clinical features and different bronchial lavage sequences as well. To explore the clinical value of MMP-7 mRNA, survivin mRNA in BLF specimens as tumor makers for earlier diagnosis of lung cancer, especialy peripheral lung cancer.
Methods
Bronchial lavage fluid(BLF) were collected from 124 cases suffering from lung cancer, 103 cases suffering from pulmonary benign diseases. Forceps biopsy(FB) were collected from 42 cases suffering from lung cancer, 30 cases suffering from pulmonary benign diseases. All specimens were deteced the expression of MMP-7, survivin messenger RNA(mRNA) with the method of reverse polymerase chain reaction(RT-PCR). The expression of MMP-7 mRNA, survivin mRNA in patients with lung cancer and non-lung cancer, the correlation between expression of MMP-7 mRNA, survivin mRNA and clinical features, different bronchial lavage sequences were studied. The results were compared with their cytopathological examinations. The clinical value of MMP-7 mRNA, survivin mRNA in BLF specimens as specific tumor makers for earlier diagnosis, especialy peripheral lung cancer was evaluated by ROC (receiver operating characteristic curve) analytical system.
Results
1. To detect MMP-7 mRNA、survivin mRNA expression in patients with lung cancer and non-lung cancer the consistencies were better in paired specimens FB and BLF(Kappa=0.419, 0.567; P=0.001, 0.000).
2. The positive rate of survivin mRNA in specimen from BLF of lung cancer 45.2%(56/124) was higher than that 18.4%(19/103) in specimen from BLF of non-lung cancer, and there was significant difference between the positive rate of survivin mRNA in specimen from BLF of lung cancer and that in specimen from BLF of non-lung cancer(χ2=18.150, P=0.000), but there was no significant difference between the positive rate of MMP-7 mRNA in specimen from BLF of lung cancer 24.2%(30/124) and that 18.4%(19/103) in specimen from BLF of non-lung cancer(χ2=1.098, P=0.295).
3. There were correlation between survivin expression and histopathological subtype(small cell lung cancer), differentiation(lower differentiation), T of TNM stages(all P<0.05). There was correlation between MMP-7 mRNA expression and smoking(P<0.05).
4. There was no difference between the positive rate of cytopathological examination (23.9%) and that (22.1%) of MMP-7 mRNA (χ2=0.100、P=0.752), while there were significant difference between the positive rate of cytopathological examination and that (43.4%) of survivin mRNA, that (51.3%) MMP-7 mRNA combined with survivin mRNA from BLF specimens (χ2=9.595, 18.121; P=0.002, 0.000 ). The positive rates of MMP-7 mRNA, survivin mRNA and MMP-7 mRNA combined with survivin mRNA from BLF specimens were 24.2%(21/124), 44.2%(38/86), 59.3%(51/86) respectively, while the positive rate of cytopathological examinations from BLF specimens was zero. The sensitivity of cytological examinations combined with detecting MMP-7 mRNA, survivin mRNA from BLF specimens was higher than that of either cytological examination or MMP-7 mRNA, survivin mRNA detection of BLF specimens alone(all P<0.05).
5. The sensitivity and specificity of the diagnosis for lung cancer by detecting MMP-7 mRNA, survivin mRNA, MMP-7 mRNA combined with survivin mRNA in BLF specimens were respectively: 24.2%, 45.2%, 52.4% and 81.6%, 81.6%, 97.1%. The sensitivity and specificity of the diagnosis for peripheral lung cancer by detecting MMP-7 mRNA, survivin mRNA, MMP-7 mRNA combined with survivin mRNA from BLF specimens were respectively: 23.1%, 35.9%, 43.6% and 85.4%, 85.4%, 98.1%.
Conclusions
Conclusions drawn from this study are as following:
1. Expression of survivin mRNA in specimens from bronchial lavage fluid(BLF) might be used as the specific molecular markers for diagnosis of lung cancer especially peripheral lung cancer because of it,s higher sensitivity and specificity. The diagnosis value of expression of MMP-7 mRNA in specimens from BLF should be studied further for it’s lower sensitivity and poor consistency.
2. It can make the diagnosis sensitivity for lung cancer especialy peripheral lung cancer improved greatly that detecting cytological examination combined with survivin mRNA, or, and with MMP-7 mRNA, and that detecting survivin mRNA combined with MMP-7 mRNA.
3. The outcome of expression of MMP-7 mRNA, survivin mRNA don't be affected by the different bronchial lavage sequences.
引文
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