KiSS-1和VEGF在涎腺黏液表皮样癌中的表达及其对血管生成的影响
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摘要
目的研究肿瘤转移抑制基因KiSS-1和血管内皮生长因子(VEGF)在涎腺黏液表皮样癌(MEC)组织中的表达情况及其对血管生成的影响。方法选择河北北方学院附属第一医院口腔科2007年6月至2016年6月收治的68例MEC患者为研究对象。应用免疫组织化学SP法检测68例MEC组织、20例正常涎腺组织中KiSS-1和VEGF的表达,统计学比较其在不同临床病理特征的MEC组织中表达阳性率的差异。光镜下计数利用CD105标记的微血管密度(MVD),统计学比较不同临床病理特征的MEC组织MVD值的差异,并观察KiSS-1和VEGF的表达对MEC组织MVD值的影响。结果 68例MEC组织中KiSS-1的阳性表达率为38.24%,明显低于正常涎腺组织的70.00%,VEGF的阳性表达率为70.59%,明显高于正常涎腺组织的10.00%,差异均有统计学意义(P<0.05)。KiSS-1的表达与MEC的淋巴结转移和TNM分期相关(P<0.05),VEGF的表达与MEC的病理分级、淋巴结转移和TNM分期相关(P<0.05);KiSS-1阳性组MVD值为(29.50±9.14),明显低于阴性组的(35.24±10.45),VEGF阳性组MVD值为(35.33±10.20),明显高于阴性组的(27.57±8.45),差异均有显著统计学意义(P<0.01);KiSS-1的表达与VEGF表达呈负相关(r_s=-0.488,P=0.000)。结论在MEC组织中KiSS-1表达的下调可能促进VEGF的表达,从而促进了MEC组织血管的生成,促进其侵袭和转移。
Objective To investigate the relationship of the expression of tumor metastasis suppressor gene kisspeptin-1(KiSS-1) and vascular endothelial growth factors(VEGF) with angiogenesis in mucoepidermoid carcinoma(MEC) of salivary glands. Methods A total of 68 MEC patients, who admitted to Department of Stomatology of the First Affiliated Hospital of Hebei North College from June 2007 to June 2016, were chosen as research objects. The expression of KiSS-1 and VEGF was detected with immunohistochemical method(SP) in 68 cases of MEC tissues and 20 cases of normal salivary gland. Statistical method was used to compare the differences of expression positive rates of KiSS-1 and VEGF in different clinical pathological types of MEC. The microvessel density(MVD) was recorded under optical microscope. Statistical method was used to compare the differences of MVD in different clinical pathological types of MEC, and to observe how the expression of KiSS-1 and VEGF affect the MVD in MEC. Results The positive expressions of KiSS-1 in MEC tissues was 38.24%, which was significantly lower than 70.00% in the normal salivary gland group(P<0.05). The positive expressions of VEGF in MEC tissues was 70.59%, which was significantly higher than 10.00% in the normal salivary gland group(P<0.05). The expression of KiSS-1 was correlated with lymph node metastasis and TNM staging(P<0.05); the expression of VEGF was correlated with pathological grade level, lymph node metastasis, TNM staging(P<0.05). The MVD in KiSS-1 positive expression group was(29.50 ± 9.14), which was significantly lower than(35.24 ± 10.45) in KiSS-1 negative expression group(P<0.05); the MVD in VEGF positive expression group was(35.33±10.20), which was significantly higher than(27.57±8.45) in VEGF negative expression group(P<0.01). The expression of KiSS-1 was negatively correlated with VEGF(r_s=-0.488, P=0.000). Conclusion The down-regulation expression of KiSS-1 in MEC of salivary glands may play a role in angiogenesis through increasing the expression of VEGF, thus promote tumor invasion and metastasis.
Objective To investigate the relationship of the expression of tumor metastasis suppressor gene kisspeptin-1(KiSS-1) and vascular endothelial growth factors(VEGF) with angiogenesis in mucoepidermoid carcinoma(MEC) of salivary glands. Methods A total of 68 MEC patients, who admitted to Department of Stomatology of the First Affiliated Hospital of Hebei North College from June 2007 to June 2016, were chosen as research objects. The expression of KiSS-1 and VEGF was detected with immunohistochemical method(SP) in 68 cases of MEC tissues and 20 cases of normal salivary gland. Statistical method was used to compare the differences of expression positive rates of KiSS-1 and VEGF in different clinical pathological types of MEC. The microvessel density(MVD) was recorded under optical microscope. Statistical method was used to compare the differences of MVD in different clinical pathological types of MEC, and to observe how the expression of KiSS-1 and VEGF affect the MVD in MEC. Results The positive expressions of KiSS-1 in MEC tissues was 38.24%, which was significantly lower than 70.00% in the normal salivary gland group(P<0.05). The positive expressions of VEGF in MEC tissues was 70.59%, which was significantly higher than 10.00% in the normal salivary gland group(P<0.05). The expression of KiSS-1 was correlated with lymph node metastasis and TNM staging(P<0.05); the expression of VEGF was correlated with pathological grade level, lymph node metastasis, TNM staging(P<0.05). The MVD in KiSS-1 positive expression group was(29.50 ± 9.14), which was significantly lower than(35.24 ± 10.45) in KiSS-1 negative expression group(P<0.05); the MVD in VEGF positive expression group was(35.33±10.20), which was significantly higher than(27.57±8.45) in VEGF negative expression group(P<0.01). The expression of KiSS-1 was negatively correlated with VEGF(r_s=-0.488, P=0.000). Conclusion The down-regulation expression of KiSS-1 in MEC of salivary glands may play a role in angiogenesis through increasing the expression of VEGF, thus promote tumor invasion and metastasis.
引文
[1]Beck BH,Welch DR.The KISS1 metastasis suppressor:a good night kiss for disseminated cancer cells[J].Eur J Cancer,2010,46(7):1283-1289.
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[3]韦存志,蔡德丰,屈进文,等.腮腺黏液表皮样癌单纯手术和术后辅助放化疗疗效和预后因素分析[J].国际肿瘤学杂志,2015,42(10):726-729.
[4]Xiao CC,Zhan KY,White-Gilbertson SJ,et al.Predictors of nodal metastasis in parotid malignancies:a national cancer data base study of 22,653 patients[J].Otolaryngol Head Neck Surg,2016,154(1):121-130.
[5]Benjamin H,Welch DR.The KISSl memstasis suppressor:a good night kiss for disseminated cancer cells[J].Eur J Cancer,2010,46(7):1283-1289.
[6]樊清波,刘红山,秦秉玉,等.Kissl在胃腺癌组织中的表达及其对胃癌细胞增殖和转移的影响[J].中华实验外科杂志,2014,31(3):489-491.
[7]Kostakis ID,Agrogiannis G,Vaiopoulos AG,et a1.KISS1 expression in colorectal cancer[J].APMIS,2013,121(10):1004-1010.
[8]Liu M,Wang S,Pan L,et al.A new model for predicting nonsentinel lymph node status in Chinese sentinel lymph node positive breast cancer patients[J].PLo S One,2014,9(8):e104117.
[9]Sun YB,Xu S.Expression of KISS1and KISSl R(GPR54)may be used as favorable prognostic markers for patients with non-small cell lung cancer[J].Int J Oneol,2013,43(2):521-530.
[10]Wang H,Jones J,Turner T,et a1.Clinical and biological signifieance of KISSl expression in prostate cancer[J].Am J Pathol,2012,180(3):1170-1178.
[11]刘敏,李嵩,赵运.人脑血管母细胞瘤中VEGF和b FGF的表达及与血管生成的关系[J].河北医科大学学报,2013,34(1):5-8.
[12]刘秀芳,徐浩.el F-4E与VEGF在卵巢恶性肿瘤组织中的表达及意义[J].中外健康文摘,2013,10(26):54.
[13]安峰,何薇薇,林媛媛,等.涎腺黏液表皮样癌中信号传导和转录激活因子3、血管内皮生长因子的表达及临床意义[J].河北医科大学学报,2015,36(5):540-546.
[14]钱立勇,温媛媛,徐勇飞.CDl05和信号传导及转录活化因子3在人脑胶质瘤组织中的表达及临床意义[J].中华实验外科杂志,2015,32(12):3173-3175.
[15]Teng Y,Mei Y,Hawthorn L,et al.WASF3 regulates mi R-200 inactivation by ZEB1 through suppression of KISS1 leading to increased invasiveness in breast cancer cells[J].Oncogene,2014,33(2):203-211.
[16]Kiriakidis S,Andreakos E,Monaco C,et a1.VEGF expresson in human macmphages is NF-kappa B-dependent:studies using adenovimses expressing the endogenous NF-kappa B inhibitor lkappa Balpha and a kinase-defective form of the lkappa B kinase 2[J].J Cell Sci,2003,116(Pt4):665-674.
[2]Weidner N.Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors[J].Breast Cancer Res Treat,1995,36(2):169-180.
[3]韦存志,蔡德丰,屈进文,等.腮腺黏液表皮样癌单纯手术和术后辅助放化疗疗效和预后因素分析[J].国际肿瘤学杂志,2015,42(10):726-729.
[4]Xiao CC,Zhan KY,White-Gilbertson SJ,et al.Predictors of nodal metastasis in parotid malignancies:a national cancer data base study of 22,653 patients[J].Otolaryngol Head Neck Surg,2016,154(1):121-130.
[5]Benjamin H,Welch DR.The KISSl memstasis suppressor:a good night kiss for disseminated cancer cells[J].Eur J Cancer,2010,46(7):1283-1289.
[6]樊清波,刘红山,秦秉玉,等.Kissl在胃腺癌组织中的表达及其对胃癌细胞增殖和转移的影响[J].中华实验外科杂志,2014,31(3):489-491.
[7]Kostakis ID,Agrogiannis G,Vaiopoulos AG,et a1.KISS1 expression in colorectal cancer[J].APMIS,2013,121(10):1004-1010.
[8]Liu M,Wang S,Pan L,et al.A new model for predicting nonsentinel lymph node status in Chinese sentinel lymph node positive breast cancer patients[J].PLo S One,2014,9(8):e104117.
[9]Sun YB,Xu S.Expression of KISS1and KISSl R(GPR54)may be used as favorable prognostic markers for patients with non-small cell lung cancer[J].Int J Oneol,2013,43(2):521-530.
[10]Wang H,Jones J,Turner T,et a1.Clinical and biological signifieance of KISSl expression in prostate cancer[J].Am J Pathol,2012,180(3):1170-1178.
[11]刘敏,李嵩,赵运.人脑血管母细胞瘤中VEGF和b FGF的表达及与血管生成的关系[J].河北医科大学学报,2013,34(1):5-8.
[12]刘秀芳,徐浩.el F-4E与VEGF在卵巢恶性肿瘤组织中的表达及意义[J].中外健康文摘,2013,10(26):54.
[13]安峰,何薇薇,林媛媛,等.涎腺黏液表皮样癌中信号传导和转录激活因子3、血管内皮生长因子的表达及临床意义[J].河北医科大学学报,2015,36(5):540-546.
[14]钱立勇,温媛媛,徐勇飞.CDl05和信号传导及转录活化因子3在人脑胶质瘤组织中的表达及临床意义[J].中华实验外科杂志,2015,32(12):3173-3175.
[15]Teng Y,Mei Y,Hawthorn L,et al.WASF3 regulates mi R-200 inactivation by ZEB1 through suppression of KISS1 leading to increased invasiveness in breast cancer cells[J].Oncogene,2014,33(2):203-211.
[16]Kiriakidis S,Andreakos E,Monaco C,et a1.VEGF expresson in human macmphages is NF-kappa B-dependent:studies using adenovimses expressing the endogenous NF-kappa B inhibitor lkappa Balpha and a kinase-defective form of the lkappa B kinase 2[J].J Cell Sci,2003,116(Pt4):665-674.