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中华诊断学电子杂志 ›› 2022, Vol. 10 ›› Issue (01) : 42 -47. doi: 10.3877/cma.j.issn.2095-655X.2022.01.009

临床研究

胰岛素样生长因子结合蛋白2和细胞外调节蛋白激酶1/2在肾透明细胞癌中的表达及其临床意义
吕建志1, 曹井贺2, 刘欢1, 王鑫哲1, 石素素1, 祝海洲3,†()   
  1. 1. 272013　济宁医学院临床医学院
    2. 272029　济宁医学院附属医院生殖医学科
    3. 272013　济宁医学院临床医学院；272029　济宁医学院附属医院泌尿外科
  • 收稿日期:2021-06-30 出版日期:2022-02-26
  • 通信作者: 祝海洲
  • 基金资助:
    济宁医学院国家自然科学基金培育项目(JYP2019KJ18); 济宁医学院教师科研扶持基金(JYFC2018KJ054)

Clinical significance of IGFBP2 and ERK1/2 expression in clear cell renal cell carcinoma

Jianzhi Lyu1, Jinghe Cao2, Huan Liu1, Xinzhe Wang1, Susu Shi1, Haizhou Zhu3,†()   

  1. 1. Clinical Medical College, Jining Medical University, Jining 272013, China
    2. Department of Reproductive Medicine, Affiliated Hospital of Jining Medical University, Jining 272029, China
    3. Clinical Medical College, Jining Medical University, Jining 272013, China; Department of Urology, Affiliated Hospital of Jining Medical University, Jining 272029, China
  • Received:2021-06-30 Published:2022-02-26
  • Corresponding author: Haizhou Zhu
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引用本文：

吕建志, 曹井贺, 刘欢, 王鑫哲, 石素素, 祝海洲. 胰岛素样生长因子结合蛋白2和细胞外调节蛋白激酶1/2在肾透明细胞癌中的表达及其临床意义[J]. 中华诊断学电子杂志, 2022, 10(01): 42-47.

Jianzhi Lyu, Jinghe Cao, Huan Liu, Xinzhe Wang, Susu Shi, Haizhou Zhu. Clinical significance of IGFBP2 and ERK1/2 expression in clear cell renal cell carcinoma[J]. Chinese Journal of Diagnostics(Electronic Edition), 2022, 10(01): 42-47.

目的

探讨胰岛素样生长因子结合蛋白2(IGFBP2)和细胞外调节蛋白激酶1/2(ERK1/2)在肾透明细胞癌(ccRCC)中的表达及其临床意义。

方法

收集2017年6月至2019年4月在济宁医学院附属医院泌尿外科行手术治疗的174例ccRCC患者的临床资料，并同期选择健康体检中心30例正常健康者的血液标本。应用免疫组织化学方法检测ccRCC患者肿瘤组织、癌旁组织(距肿瘤边缘2 cm)中IGFBP2和ERK1/2的表达情况，并与肿瘤临床分期、组织学分级及肿瘤大小进行相关性分析；同时应用酶联免疫吸附试验(ELISA)检测ccRCC患者及健康者血清中IGFBP2、ERK1、ERK2的水平。

结果

IGFBP2和ERK1/2在ccRCC组织中的表达阳性率[87.93%(153/174)，80.46%(140/174)]比癌旁组织[6.67%(2/30)，10.00%(3/30)]高，均差异有统计学意义(χ2＝92.59，65.87；均P<0.01)。IGFBP2和ERK1/2在直径≥4 cm的肿瘤中的表达阳性率[高于<4 cm的肿瘤表达阳性率，均差异有统计学意义(χ2＝7.81，13.02；均P<0.05)；IGFBP2和ERK1/2的表达在患者的年龄(χ2＝0.78，0.60)、性别(χ2＝0.05，1.33)、肿瘤左右侧位置(χ2＝0.96，0.57)中比较均差异无统计学意义(均P>0.05)。IGFBP2及ERK1/2的阳性表达率随着临床分期及组织学分级的升高而升高，且在不同组织分级(Z＝-8.17，-3.80)和不同临床分期(Z＝-5.63，-9.94)间差异具有统计学意义(均P<0.05)。IGFBP2和ERK1/2在ccRCC组织中的表达呈正相关(r＝0.32，P<0.05)。ELISA实验结果表明，IGFBP2、ERK1、ERK2在ccRCC患者血清中的表达水平[(858.33±132.89)μg/L，(12.49±1.22)μg/L，(153.61±33.37)ng/L]较健康对照组[(267.65±86.56)μg/L，(8.69±1.80)μg/L，(105.63±12.03)ng/L]明显升高，均差异具有统计学意义(t＝11.78，5.53，4.28；均P<0.05)。

结论

IGFBP2和ERK1/2在ccRCC患者血清及肿瘤组织中均表达升高，组织中组织学分级越高、临床分期越晚、肿瘤体积越大，阳性表达率越高，两者在肿瘤的进展中可能起到协同作用。

关键词: 癌，肾细胞, 胰岛素样生长因子结合蛋白2, 细胞外调节蛋白激酶1/2, 免疫组织化学, 酶联免疫吸附测定
Objective

To explore the expression and clinical significance of IGFBP2 and ERK1/2 in the clear cell renal cell carcinoma (ccRCC).

Methods

Clinical data of 174 ccRCC patients who underwent surgical treatment in the Department of Urology, Affiliated Hospital of Jining Medical University from June 2017 to April 2019 were selected, and the blood samples of 30 healthy individuals were selected in the Health Examination Center during the same period. The expressions of IGFBP2 and ERK1/2 in ccRCC and adjacent (2 cm from the edge of the tumor) tissues were assessed by immunohistochemistry and the correlation with clinical stage, histological grade and tumour size was analyzed. Serum levels of IGFBP2, ERK1 and ERK2 were also measured by ELISA in ccRCC patients and healthy controls.

Results

The positive ratios of IGFBP2 and ERK1/2 expression in ccRCC tissues (87.93%, 80.46%) were higher than those in precancerous tissues (6.67%, 10.00%), all of which were significantly different (χ2=92.59, 65.87, all P<0.01). The positive ratios of IGFBP2 and ERK1/2 expression in tumors larger than 4 cm were higher than those in tumors smaller than 4 cm, all of which were statistically significant (χ2=7.81, 13.02, all P<0.05). There were no significant differences in the expression of IGFBP2 and ERK1/2 at patients′ age (χ2=0.78, 0.60), gender (χ2=0.05, 1.33), or tumor location (χ2=0.96, 0.57) (all P>0.05). The positive expression rates of IGFBP2 and ERK1/2 increased with higher clinical stage and histological grade, and were statistically significant between groups in different grades (Z=-8.17, -3.80, all P<0.05) and different stages(Z=-5.63, -9.94, all P<0.05). The expression of IGFBP2 was significantly positively correlated with ERK1/2 in ccRCC tissues (r=0.32, P<0.05). ELISA showed that IGFBP2, ERK1, ERK2 were significantly increased in ccRCC patients [(858.33±132.89)μg/L, (12.49±1.22)μg/L, (153.61±33.37)ng/L] compared with healthy controls [(267.65±86.56)μg/L, (8.69±1.80)μg/L, (105.63±12.03)ng/L], all of which were significantly different (t=11.78, 5.53, 4.28, all P<0.05).

Conclusion

The expressions of IGFBP2 and ERK1/2 are elevated in serum and tumor tissues in ccRCC patients, and their positive expressions in tumor tissues are correlated with histological grade, clinical stage, and tumor size, the histological grade, later clinical stage, and larger tumor volume, the higher the positive expression rates of both suggesting that both may play a synergistic role in tumor progression.

Key words: Carcinoma, renal cell, Insulin-like growth factor binding proteins 2, Extracellular regulated protein kinase 1/2, Immunohistochemistry, Enzyme-linked immunosorbent assay
图1 IGFBP2和ERK1/2在ccRCC及癌旁组织中的表达情况注：a图示IGFBP2在ccRCC组织中表达阳性，在细胞核及细胞质中表现为棕黄色颗粒样染色(箭头所示)；b图示ERK1/2在ccRCC组织中表达阳性，多数于细胞质中表现为棕褐色颗粒样染色(箭头所示)；c图示IGFBP2在癌旁组织表达阴性；d图示ERK1/2在癌旁组织表达阴性；ccRCC为肾透明细胞癌；IGFBP2为胰岛素样生长因子结合蛋白2；ERK1/2为细胞外调节蛋白激酶1/2
表1 IGFBP2和ERK1/2在ccRCC及癌旁组织中的表达比较(例，%)
组别 例数 IGFBP2 χ2值 P值 ERK1/2 χ2值 P值
阳性 阴性 阳性 阴性
ccRCC组织组 174 153(87.93) 21(12.07) 92.59 <0.01 140(80.46) 34(19.54) 65.87 <0.01
癌旁组织组 30 2(6.67) 28(93.33) 3(10.00) 27(90.00)
表2 IGFBP2和ERK1/2在不同临床类型ccRCC患者中的表达(例)
项目 例数 IGFBP2 χ2值 P值 ERK1/2 χ2值 P值
阳性 阴性 阳性 阴性
年龄(岁)       0.78 >0.05     0.60 >0.05
  <60 92 79 13     72 20    
  ≥60 82 74 8     68 14    
性别       0.05 >0.05     1.33 >0.05
  男 112 98 14     93 19    
  女 62 55 7     47 15    
位置       0.96 >0.05     0.57 >0.05
  左 92 83 9     76 16    
  右 82 70 12     64 18    
肿瘤直径(cm)       7.81 <0.05     13.02 <0.05
  ≥4 99 93 6     89 10    
  <4 75 60 15     51 24    
表3 IGFBP2和ERK1/2在不同组织学分级及临床分期的ccRCC患者中的表达(例)
分组 例数 IGFBP2 χ2值 P值 ERK1/2 χ2值 P值
阳性 阴性 阳性 阴性
组织学分级       -8.17 <0.05     -3.80 <0.05
  Ⅰ 79 50 29     37 42    
  Ⅱ 80 66 14     52 28    
  Ⅲ 12 11 1     10 2    
  Ⅳ 3 3 0     3 0    
临床分期       -5.63 <0.05     -9.94 <0.05
  Ⅰ期 138 72 66     65 73    
  Ⅱ期 27 21 6     20 7    
  Ⅲ期 5 4 1     4 1    
  Ⅳ期 4 4 0     4 0    
表4 ccRCC组及健康对照组血清IGFBP2、ERK1、ERK2水平的比较(±s)
组别 例数 IGFBP2(μg/L) ERK1(μg/L) ERK2(ng/L)
ccRCC组 174 858.33±132.89 12.49±1.22 153.61±33.37
健康对照组 30 267.65±86.56 8.69±1.80 105.63±12.03
t值   11.78 5.53 4.28
P值   <0.05 <0.05 <0.05
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