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中华妇幼临床医学杂志(电子版)

Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition) ›› 2014, Vol. 10 ›› Issue (02): 204 -209. doi: 10.3877/cma.j.issn.1673-5250.2014.02.017

Special Issue: ；

Original Article

Expression and Significance of Stromal Cell Derived Factor-1, Chemokine CXC Motif Receptor-4, Matrix Metalloproteinase-2 and Ki-67 in Cervical Squamous Cancer

Huiqing Ma1(), Xiufeng Yang1, Haiyan Cheng1   

  1. 1. Department of Gynecology, Second Affiliated Hospital, Medical School of Qingdao University, Qingdao 266042, Shandong Province, China
  • Received:2013-10-05 Revised:2014-02-06 Published:2014-04-01
  • Corresponding author: Huiqing Ma
  • About author:
    (Corresponding author: Ma Huiqing, Email: )
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Objective

To study the expression of stromal cell derived factor (SDF)-1, chemokine CXC motif receptor(CXCR)-4, matrix metalloproteinase (MMP)-2 and Ki-67 and their association with clinical pathological features in human cervical squamous cancer tissues.

Methods

From January 2010 to September 2012, a total of 60 cases samples with squamous carcinoma of the cervix which were confirmed by histopathology were enrolled into this study (study group) . At the same time, another 60 cases samples with benign uterine diseases were included into control group. There had no significant differences among age and other clinical information between two groups (P>0.05) . The expression of SDF-1, CXCR4, MMP-2 and Ki-67 were detected between two groups by immunohistochemistry and the correlation analysis was conducted. The study protocol was approved by the Ethical Review Board of Investigation in Second Affiliated Hospital, Medical School of Qingdao University. Informed consent was obtained from all participates .

Results

The positive expression rates of SDF-1, CXCR4, MMP-2 and Ki-67 were 90.00%, 68.33 %, 70.00% and 86.67% in study group, 40.00%, 8.33%, 13.33% and 1.67% in control group, respectively. Significant differences were observed between two groups (χ2 =9.63, 7.04, 4.00, 4.00; P< 0.05) . Expressions of SDF-1, CXCR4, MMP-2 and Ki-67 in cervical cancer tissues with pelvic lymph nodes metastasis were higher than those in cervical cancer tissues without pelvic lymph node metastasis, which were closely associated with pelvic lymph node metastasis (χ2 =16.692, P<0.001; χ2=8.496, P<0.01; χ2 =4.762, P<0.001; χ2 =6.125, P<0.05) . The expression of SDF-1 was significantly correlated with CXCR4, MMP-2 and Ki-67 (r=0.586, P =0.002; r =0.419, P =0.025; r =0.645, P <0.001) .

Conclusions

Expressions of SDF-1, CXCR4, MMP-2 and Ki-67 of cervical squamous cancer tissues are involved in tumor genesis and associated with invasion and lymphnode metastasis of cervical cancer, which can serve as biomarkers for diagnosis and prediction of lymph node metastasis. Furthermore, the expression of SDF-1/ CXCR4 in cervical cancer may promote the tumor invasion and metastasis through the secretion of MMP-2 and Ki-67, suggesting that SDF-1 may be an important target for drug therapy.

Key words: Uterine cervical neoplasms, Stromal cell derived factor-1, Chemokine CXC motif receptor-4, Matrix metalloproteinases, Ki-67, Immunohistochemistry
图1 SDF-1在宫颈癌组织中的表达（10 × 10）
Figure 1 Positive expression of SDF-1 in cervical squamous cancer （10 × 10）
图2 CXCR4在宫颈癌组织中的表达（10 × 10）
Figure 2 Positive expression of CXCR4 in cervical squamous cancer （10 × 10）
表1 SDF-1在宫颈鳞癌组织和正常宫颈组织中的表达[n（%）]
Table 1 Expression of SDF-1 in cervical squamous cancer and normal cervix tissue [n（%）]
组别 n (-) (+ ) (+ + ) (+ + + ) 阳性率(%)
研究组 60 6(10.00) 11(18.33) 19(31.67) 24(40.00) 90.00
对照组 60 36(60.00) 14(23.33) 7(11.67) 3 (5.00) 40.00
χ2 　 　 　 　 　 9.63
P 　 　 　 　 　 <0.01
表2 CXCR4在宫颈鳞癌组织和正常宫颈组织中的表达[n（%）]
Table 2 Expression of CXCR4 in cervical squamous cancer and normal cervix tissue [n（%）]
组别 n (-) (+ ) (+ + ) (+ + + ) 阳性率(%)
研究组 60 19(31.67) 6(10.00) 19(31.67) 16(26.67) 68.33
对照组 60 50(83.33) 5 (8.33) 3 (5.00) 2 (3.33) 8.33
χ2 　 　 　 　 　 7.04
P 　 　 　 　 　 <0.01
表3 SDF-1、CXCR4的表达水平与宫颈鳞癌的临床病理因素的关系[n （％）]
Table 3 Relationship between clinicopathological features and expression levels of SDF-1，CXCR4 in cervical squamous cancer[n（％）]
临床病理参数 n SDF-1表达 χ2 P CXCR4表达 χ2 P
(-) (+ ) (+ + ) (+ + + ) (-) (+ ) (+ + ) (+ + + )
组织学分级 　 　 　 　 　 　 　 　 　 　 　 　 　
　 Ⅰ 19 3(15.79) 2(10.53) 5(26.32) 9(47.37) 0.509 >0.05 5(26.32) 3(15.79) 5(26.32) 6(31.58) 0.201 >0.05
　 Ⅱ 23 1 (4.35) 5(21.74) 8(34.72) 9(39.13) 　 　 8(34.78) 2 (8.70) 7(30.43) 6(26.09) 　 　
　 Ⅲ 18 2(11.11) 4(22.22) 6(33.33) 6(33.33) 　 　 6(33.33) 1 (5.06) 7(38.89) 4(22.22) 　 　
肿瘤直径(cm) 　 　 　 　 　 　 　 　 　 　 　 　 　
　 <2 27 3(11.11) 4(14.81) 9(33.33) 11(40.74) －0.988 >0.05 12(44.44) 1 (3.70) 9(33.33) 5(18.52) -118.030 >0.05
　 2~4 22 1 (4.55) 5(22.73) 6(27.27) 10(45.45) 　 　 5(22.73) 3(13.64) 7(31.82) 7(31.82) 　 　
　 >4 11 2(18.18) 2(18.18) 4(36.36) 3(27.27) 　 　 2(18.18) 2(18.18) 3(27.27) 4(36.36) 　 　
临床分期 　 　 　 　 　 　 　 　 　 　 　 　 　
　 ⅠA2 16 1 (6.25) 2(12.50) 6(37.50) 7(43.75) 5.582 >0.05 5(31.25) 1 (6.25) 5(31.25) 5(31.25) -32.003 >0.05
　 ⅠB 30 3(10.00) 4(13.33) 8(26.67) 15(50.00) 　 　 10(33.33) 3(10.00) 9(30.00) 8(26.67) 　 　
　 ⅡA 14 2(14.29) 5(35.71) 5(35.71) 2(14.29) 　 　 4(28.57) 2(14.29) 5(35.71) 3(21.43) 　 　
淋巴结转移 　 　 　 　 　 　 　 　 　 　 　 　 　
　 有 31 2 (6.45) 3 (9.68) 9(29.03) 17(54.84) 16.692 <0.001 12(38.71) 1 (3.23) 9(29.03) 5(16.13) 8.496 <0.01
　 无 29 5(17.24) 9(31.03) 11(37.93) 4(13.79) 　 　 5(17.24) 3(10.34) 7(24.14) 7(24.14) 　 　
图3 MMP-2在宫颈癌组织中的表达（10 × 10）
Figure 3 Positive expression of MMP-2 in cervical squamous cancer （10 × 10）
图4 Ki-67在宫颈癌组织中的表达（10 × 10）
Figure 4 Positive expression of Ki67 in cervical squamous cancer （10 × 10）
表4 MMP-2、Ki-67在宫颈鳞癌组织和正常宫颈组织中的表达[n（%）]
Table 4 Expression of MMP-2, Ki-67 in cervical squamous cancer and normal cervix tissue [n（%）]
组别 n MMP-2表达 Ki-67表达
(-) (+ ) (+ + ) 阳性率(％) (-) (+ ) (+ + ) (+ + + ) 阳性率(％)
研究组 60 18(30.00) 17(28.33) 25(41.67) 70.00 8(13.33) 16(26.67) 20(33.33) 16(26.67) 86.67
对照组 60 52(86.67) 6(10.00) 2(33.33) 13.33 59(98.33) 1(1.67) 0(0.00) 0(0.00) 1.67
χ2 　 　 　 　 4.00 　 　 　 　 <0.05
P 　 　 　 　 <0.05 　 　 　 　 <0.05
表5 MMP-2、Ki-67的表达水平与宫颈鳞癌的临床病理特征的关系[n（％）]
Table 5 Relationship between clinicopathological features and expression levels of MMP-2, Ki-67 in cervical squamous cancer [n（％）]
临床病理参数 n MMP-2 χ2 P Ki-67 χ2 P
(-) (+ ) (+ + ) (-) (+ ) (+ + ) (+ + + )
组织学分级 　 　 　 　 　 　 　 　 　 　 　 　
　 Ⅰ 19 7(36.84) 5(26.32) 7(36.84) 2.547 0.636 6(31.58) 9(47.37) 4(21.05) 0 (0.00) 25.541 0.000
　 Ⅱ 23 6(26.09) 5(21.74) 12(52.17) 　 　 2 (8.70) 6(26.09) 9(39.13) 6(26.09) 　 　
　 Ⅲ 18 5(27.78) 7(38.89) 6(33.33) 　 　 0 (0.00) 1 (5.56) 7(38.89) 10(55.56) 　 　
肿瘤大小(cm) 　 　 　 　 　 　 　 　 　 　 　 　
　 <2 27 7(25.93) 7(25.93) 13(48.15) 1.459 0.834 3(11.11) 9(33.33) 9(33.33) 6(22.22) 2.659 0.850
　 2~4 22 7(31.82) 6(27.27) 9(40.91) 　 　 3(13.64) 6(27.27) 7(31.82) 6(27.27) 　 　
　 >4 11 4(36.36) 4(36.36) 3(27.27) 　 　 2(18.18) 1 (9.09) 4(36.36) 4(36.36) 　 　
临床分期 　 　 　 　 　 　 　 　 　 　 　 　
　 ⅠA2 16 10(62.50) 5(31.25) 1 (6.25) 16.077 0.003 2(12.50) 3(18.75) 6(37.50) 5(31.25) 3.587 0.732
　 ⅠB 30 5(16.67) 10(33.33) 15(50.00) 　 　 4(13.33) 11(36.67) 9(30.00) 6(20.00) 　 　
　 ⅡA 14 3(21.43) 2(14.29) 9(64.29) 　 　 2(14.29) 2(14.29) 5(35.71) 5(35.71) 　 　
淋巴结转移 　 　 　 　 　 　 　 　 　 　 　 　
　 有 31 5(16.13) 8(25.81) 18(58.04) 4.762 <0.001 0 (0.00) 5(16.13) 13(41.94) 13(41.94) 6.125 <0.05
　 无 29 13(44.83) 9(31.03) 7(24.14) 　 　 8(27.59) 11(37.93) 7(24.14) 3(10.34) 　 　
表6 宫颈鳞癌组织中SDF-1表达水平与CXCR4、MMP-2及Ki-67表达水平的相关性比较（n）
Table 6 Correlation between the expression levels of SDF-1 and CXCR4, MMP-2, Ki-67 in cervical squamous cancer tissues （n）
SDF-1 CXCR4 r P MMP-2 r P Ki-67 r P
(-) (+ ) (+ + ) (+ + + ) (-) (+ ) (+ + ) (-) (+ ) (+ + ) (+ + + )
(-) 5 1 0 0 0.586 0.002 5 1 0 0.419 0.025 4 1 1 0 0.645 <0.001
(+ ) 7 1 2 1 　 　 5 3 3 　 　 3 4 4 0 　 　
(+ + ) 4 3 9 3 　 　 5 4 10 　 　 1 9 5 4 　 　
(+ + + ) 3 1 8 12 　 　 3 9 12 　 　 0 2 10 12 　 　
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