VEGF、SMRP、HE4及CA125的检测在卵巢癌诊治监测中的价值
发布时间：2018-07-25 08:52
【摘要】：卵巢癌在是临床妇科常见的恶性肿瘤，其发病率高，在女性恶性肿瘤中占2.4%～5.6%，因其深居盆腔，早期无特异症状，约60～70%患者发现时已属晚期，所以早期诊断困难；即使有效治疗，仍有70%左右患者在缓解后复发。死亡率一直居女性生殖道肿瘤的第一位[1]。据统计资料表明，I～II期卵巢癌经手术化疗后5年生存率可以达到80~95%,而III～IV期仅为20～30%[2]。所以早发现、早诊断、早治疗及术后疗效监测是提高患者生存率的关键，肿瘤标志物的检测在其诊治中有着非常重要的意义，多数学者主张采用联合检测肿瘤标志物的方法，可弥补单项检测的不足，有助于提高肿瘤检出率。 目的研究显示卵巢肿瘤发病率有逐年上升的趋势，每年因卵巢癌致死的患者在各类女性生殖器恶性肿瘤患者中占据第一位。所以对于卵巢癌的诊断和积极治疗是有着很重要的意义的。从分子水平上探索卵巢癌的发生机制，是近些年来研究的热点。正是因为某些生物标志物在人体病变中表达率异常，所以可选其进行检验，以此来判断病变的可能、进展以及据此制定治疗方案等。本研究运用血管内皮细胞生长因子(VEGF)、血清间皮素相关蛋白（SMRP）、人类附睾蛋白4（HE4）和跨膜糖蛋白(CA125)的检测，观察四者在卵巢癌诊治中的作用，为诊断和治疗该病提供一定的理论依据。 方法收集靖江市人民医院2010年1月到2013年12月卵巢癌患者、良性卵巢病变患者（后均经过病理确诊）以及正常体检者的血清进行检测，对其检测结果进行回顾性分析，这三组患者分为卵巢癌组、卵巢良性病变组和正常对照组。采集受试者空腹静脉血5mL，离心后上清液置入-80摄氏度冰箱保存，5天内检测；运用瑞典康乃格公司生产的相关试剂盒进行肿瘤标志物血管内皮细胞生长因子(VEGF)、血清间皮素相关蛋白（SMRP）、人附睾蛋白4（HE4）的测定，用化学发光法测定CA125；研究数据统计学处理采用SPSS19.0进行统计分析。组间样本用χ2检验；数据符合正态性，方差齐性时采用t检验进行统计分析，如不符合正态分布，则用Wilcoxon秩和检验进行统计分析。 结果（1）VEGF在卵巢癌组中的表达水平为238.14±17.32pg/L，在良性病变组的表达水平为189.32±16.38pg/L，均显著高于正常对照组的110.68±12.28pg/L(P0.05)。而在卵巢癌组和良性病变组中的表达差异不明显，无统计学意义(P0.05)。SMRP在观察组的表达明显高于其他两组，有统计学意义(P0.05)；在良性病变组和正常对照组中的表达无明显差异(P0.05)。HE4在卵巢癌组中的表达明显高于其他两组，而在正常对照组和良性病变组中的表达差异不明显，无统计学意义(P0.05)；CA125在正常对照组的表达非常低，在卵巢癌组中的表达与良性病变组相比，有明显差异；CA125在卵巢癌组的阳性率(73.0%)显著高于良性病变组(19.0%)和正常对照(2.0%)(P0.05)，但是良性病变组的假阳性率极高，明显高于其他两组(P0.05)。（2）卵巢癌患者CA125的检测值在术后以及化疗四周后明显下降，与术前检测值有明显差异（P0.05），VEGF、SMRP、HE4的检测值在术后以及化疗四周后也有下降，但是三个时间点的检测值相比，并无明显差异（P0.05）。有3例卵巢癌术后监测中出现阳性并呈上升趋势，后经临床检查如CT，B超或手术后病理检测确定为肿瘤复发或发生转移；（3）在不同病理分级中，由高分化癌到中分化癌再到低分化癌，HE4的表达逐渐升高，并且统计学有明显差异（P0.05），而VEGF、SMRP、CA125三者的表达均未见明显差异（P0.05）；而在不同分期及分型的卵巢癌患者中，其血清HE4的表达无明显差异。VEGF在不同类型不同分期不同分级的卵巢癌患者血清中的表达无明显差异，而SMRP、CA125在卵巢上皮性肿瘤患者血清中的表达与其他类型卵巢癌患者血清中的表达相比有明显差异。CA125在不同分期的卵巢癌患者血清中的表达有明显差异，分期越晚，表达越高。（4）单独或是联合检测卵巢癌患者中的血清标志物含量，敏感性、特异性和准确度比较，联合检测的准确率均高于单独检测，但是在敏感性和特异性方面，四者联合检测与单独检测并无差异，而HE4+CA125联合则在这两方面均显著高于单独检测，说明这两者联合的成本低廉，且准确度，特异性和敏感性均最合理。 结论 1.VEGF在卵巢癌组中和在良性病变组的表达水平均显著高于正常对照组。而在卵巢癌组和良性病变组中的表达差异不明显，其无法作为卵巢癌的单一生物标志物。 2.HE4在不同病理分级中，表达有明显差异，而VEGF、SMRP、CA125三者的表达均未见明显差异，说明其在卵巢癌的病理分级中有着较好的检测价值。 3.CA125在卵巢癌组的阳性率显著高于良性病变组和正常对照组，且检测值在术后一周以及化疗3周化疗四次后明显下降，与术前检测值有明显差异，且有3例卵巢癌术后监测中出现阳性并呈上升趋势，后经临床检查如CT，B超或手术后病理检测认定为肿瘤复发或发生转移，说明其在卵巢癌术后监测预知复发方面有意义。CA125在上皮性卵巢癌患者血清中的表达明显高于其他类型卵巢癌，说明其作为卵巢上皮性肿瘤的血清标志物检测优越性明显。CA125在卵巢癌不同分期的表达有明显差异，分期越晚，表达越高。说明其在卵巢癌的诊断、评估疗效、估计复发与预后方面发挥了重要的作用[3]。 4.虽然CA125在卵巢癌尤其是上皮性卵巢癌患者血清中的表达很明显，但其在良性病变组检测中的假阳性率较高，所以需要与其他标志物进行联合，以筛选出最为合适的标志物，，提高敏感性、特异性和检测准确性，结果提示HE4+CA125联合则在这两方面均显著高于单独检测，说明这两者联合的成本低廉，且准确度，特异性和敏感性均最合理。
[Abstract]:Ovarian cancer is a common malignant tumor in clinical gynecology, with high incidence and 2.4% ~ 5.6% in female malignant tumor. Because of its deep pelvic cavity and no specific symptoms at early stage, about 60 ~ 70% patients are found in late stage, so early diagnosis is difficult. Even if effective treatment, there are still about 70% patients relapsed after remission. The mortality rate has been living in women all the time. The first [1]. statistics of Paragonimus tumor show that the 5 year survival rate of ovarian cancer in I to II stage can reach 80~95%, while the III to IV period is only 20 to 30%[2]., so early diagnosis, early diagnosis, early treatment and postoperative monitoring are the key to improve the patient's survival rate, and the detection of swollen tumor markers is very important in the diagnosis and treatment of the patients. The majority of scholars advocate that the method of combined detection of tumor markers can make up for the deficiency of single detection and improve the detection rate of tumors.
Objective to show that the incidence of ovarian tumors is increasing year by year. The patients who died from ovarian cancer each year occupy the first place in all kinds of female genital malignant tumors. Therefore, the diagnosis and active treatment of ovarian cancer are of great significance. This study uses vascular endothelial growth factor (VEGF), serum EPI related protein (SMRP), human epididymin 4 (HE4) and spans as a result of the abnormal expression of certain biomarkers in human lesions. Detection of membrane glycoprotein (CA125) to observe the role of the four in the diagnosis and treatment of ovarian cancer, and provide a theoretical basis for the diagnosis and treatment of the disease.
Methods the ovarian cancer patients in Jingjiang people's Hospital from January 2010 to December 2013, the patients with benign ovarian diseases (all after pathological diagnosis) and the normal physical examination were tested, and the results were analyzed retrospectively. The three groups were divided into ovarian cancer group, benign ovarian disease group and normal control group. Fasting venous blood 5mL, the centrifuge supernatant was stored in -80 centigrade refrigerator for 5 days after centrifugation, and the blood vessel endothelial growth factor (VEGF), serum mesothelin related protein (SMRP), human epididymal egg white 4 (HE4) were measured with the related kit produced by Swedish Connecticut company, and the number of CA125 was determined by chemiluminescence method. According to statistical analysis, statistical analysis was carried out by SPSS19.0. The inter group samples were tested by x 2; the data were in conformity with normality, and the t test was used to analyze the variance when the variance was homogeneous. If the normal distribution was not conformed to the normal distribution, the statistical analysis was carried out with the Wilcoxon rank sum test.
Results (1) the expression level of VEGF in the ovarian cancer group was 238.14 + 17.32pg/L, and the expression level in the benign group was 189.32 + 16.38pg/L, which was significantly higher than that in the normal control group (110.68 + 12.28pg/L) (P0.05), but the expression difference between the ovarian cancer group and the benign lesion group was not obvious, and there was no statistical significance (P0.05).SMRP in the observation group. The expression of.HE4 in the benign lesion group and the normal control group was significantly higher than that of the other two groups (P0.05), and the expression of.HE4 in the ovarian cancer group was significantly higher than that of the other two groups, but the expression difference between the normal control group and the benign group was not significant (P0.05); CA125 was in the normal control group. The expression was very low in the ovarian cancer group. The positive rate of CA125 in the ovarian cancer group (73%) was significantly higher than that in the benign lesion group (19%) and the normal control (2%) (P0.05), but the false positive rate of the benign lesion group was very high, obviously higher than that of the other two groups (P0.05). (2) the detection value of CA125 in the ovarian cancer patients. There was a significant decrease after the operation and after the chemotherapy (P0.05). The detection values of VEGF, SMRP, and HE4 decreased after the operation and after chemotherapy, but there was no significant difference between the three time points. There were 3 cases of ovarian cancer monitoring positive and upward trend after surgery. For example, CT, B ultrasound or postoperative pathological examination confirmed the recurrence or metastasis of the tumor. (3) in different pathological grades, the expression of HE4 increased gradually from highly differentiated to medium to low differentiated carcinoma (P0.05), but there was no significant difference in the expression of VEGF, SMRP and CA125 (P0.05), but in different stages and in different stages. There was no significant difference in the expression of serum HE4 in the patients with ovarian cancer, and there was no significant difference in the expression of.VEGF in the sera of different stages and different stages of ovarian cancer. The expression of SMRP, CA125 in the serum of the ovarian epithelial tumor patients was significantly different from that in the serum of other types of ovarian cancer patients.CA125 The expression of serum in patients with ovarian cancer in different stages was significantly different, the higher the expression was, the higher the expression was. (4) the ratio of serum markers, sensitivity, specificity and accuracy in patients with ovarian cancer was higher than that of the single test. The accuracy of the combined detection was higher than that of the single test, but the sensitivity and specificity of the four were combined. There was no difference from the single test, but the combination of HE4+CA125 was significantly higher than the single test in these two aspects, indicating that the combination of the two was low cost, and the accuracy, specificity and sensitivity were the most reasonable.
conclusion
The expression level of 1.VEGF in the ovarian cancer group and in the benign lesion group was significantly higher than that in the normal control group, but the difference in the expression of the ovarian cancer group and the benign lesion group was not obvious, and it could not be used as a single biomarker of ovarian cancer.
There were significant differences in the expression of 2.HE4 in different pathological grades, but there was no significant difference in the expression of VEGF, SMRP, and CA125 three, indicating that it has a good detection value in the pathological classification of ovarian cancer.
The positive rate of 3.CA125 in the ovarian cancer group was significantly higher than that in the benign disease group and the normal control group, and the detection value decreased obviously after one week after the operation and the chemotherapy for four times after 3 weeks of chemotherapy. There was a significant difference between the detection value and the preoperative detection value, and 3 cases of ovarian cancer were positive in the postoperative monitoring and showed an upward trend. After the clinical examination, such as CT, B ultrasound, or postoperative pathological examination. It was found that the recurrence or metastasis of the tumor showed that the expression of.CA125 in the sera of the patients with epithelial ovarian cancer was significantly higher than that of other types of ovarian cancer. It showed that the serum markers of ovarian epithelial tumor were superior to the expression of.CA125 in different stages of ovarian cancer. There is a significant difference. The higher the stage, the higher the expression. It indicates that it plays an important role in the diagnosis, evaluation of curative effect, prognosis and prognosis of ovarian cancer. [3].
4. although the expression of CA125 in the serum of ovarian cancer, especially in patients with epithelial ovarian cancer is obvious, the false positive rate in the benign lesion group is high, so it is necessary to combine with other markers to screen out the most suitable markers and improve the sensitivity, specificity and accuracy of detection. The results suggest that the combination of HE4+CA125 is in combination. These two aspects were significantly higher than the independent tests, indicating that the combination of these two methods was cheap, and the accuracy, specificity and sensitivity were the most reasonable.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.31
[Abstract]:Ovarian cancer is a common malignant tumor in clinical gynecology, with high incidence and 2.4% ~ 5.6% in female malignant tumor. Because of its deep pelvic cavity and no specific symptoms at early stage, about 60 ~ 70% patients are found in late stage, so early diagnosis is difficult. Even if effective treatment, there are still about 70% patients relapsed after remission. The mortality rate has been living in women all the time. The first [1]. statistics of Paragonimus tumor show that the 5 year survival rate of ovarian cancer in I to II stage can reach 80~95%, while the III to IV period is only 20 to 30%[2]., so early diagnosis, early diagnosis, early treatment and postoperative monitoring are the key to improve the patient's survival rate, and the detection of swollen tumor markers is very important in the diagnosis and treatment of the patients. The majority of scholars advocate that the method of combined detection of tumor markers can make up for the deficiency of single detection and improve the detection rate of tumors.
Objective to show that the incidence of ovarian tumors is increasing year by year. The patients who died from ovarian cancer each year occupy the first place in all kinds of female genital malignant tumors. Therefore, the diagnosis and active treatment of ovarian cancer are of great significance. This study uses vascular endothelial growth factor (VEGF), serum EPI related protein (SMRP), human epididymin 4 (HE4) and spans as a result of the abnormal expression of certain biomarkers in human lesions. Detection of membrane glycoprotein (CA125) to observe the role of the four in the diagnosis and treatment of ovarian cancer, and provide a theoretical basis for the diagnosis and treatment of the disease.
Methods the ovarian cancer patients in Jingjiang people's Hospital from January 2010 to December 2013, the patients with benign ovarian diseases (all after pathological diagnosis) and the normal physical examination were tested, and the results were analyzed retrospectively. The three groups were divided into ovarian cancer group, benign ovarian disease group and normal control group. Fasting venous blood 5mL, the centrifuge supernatant was stored in -80 centigrade refrigerator for 5 days after centrifugation, and the blood vessel endothelial growth factor (VEGF), serum mesothelin related protein (SMRP), human epididymal egg white 4 (HE4) were measured with the related kit produced by Swedish Connecticut company, and the number of CA125 was determined by chemiluminescence method. According to statistical analysis, statistical analysis was carried out by SPSS19.0. The inter group samples were tested by x 2; the data were in conformity with normality, and the t test was used to analyze the variance when the variance was homogeneous. If the normal distribution was not conformed to the normal distribution, the statistical analysis was carried out with the Wilcoxon rank sum test.
Results (1) the expression level of VEGF in the ovarian cancer group was 238.14 + 17.32pg/L, and the expression level in the benign group was 189.32 + 16.38pg/L, which was significantly higher than that in the normal control group (110.68 + 12.28pg/L) (P0.05), but the expression difference between the ovarian cancer group and the benign lesion group was not obvious, and there was no statistical significance (P0.05).SMRP in the observation group. The expression of.HE4 in the benign lesion group and the normal control group was significantly higher than that of the other two groups (P0.05), and the expression of.HE4 in the ovarian cancer group was significantly higher than that of the other two groups, but the expression difference between the normal control group and the benign group was not significant (P0.05); CA125 was in the normal control group. The expression was very low in the ovarian cancer group. The positive rate of CA125 in the ovarian cancer group (73%) was significantly higher than that in the benign lesion group (19%) and the normal control (2%) (P0.05), but the false positive rate of the benign lesion group was very high, obviously higher than that of the other two groups (P0.05). (2) the detection value of CA125 in the ovarian cancer patients. There was a significant decrease after the operation and after the chemotherapy (P0.05). The detection values of VEGF, SMRP, and HE4 decreased after the operation and after chemotherapy, but there was no significant difference between the three time points. There were 3 cases of ovarian cancer monitoring positive and upward trend after surgery. For example, CT, B ultrasound or postoperative pathological examination confirmed the recurrence or metastasis of the tumor. (3) in different pathological grades, the expression of HE4 increased gradually from highly differentiated to medium to low differentiated carcinoma (P0.05), but there was no significant difference in the expression of VEGF, SMRP and CA125 (P0.05), but in different stages and in different stages. There was no significant difference in the expression of serum HE4 in the patients with ovarian cancer, and there was no significant difference in the expression of.VEGF in the sera of different stages and different stages of ovarian cancer. The expression of SMRP, CA125 in the serum of the ovarian epithelial tumor patients was significantly different from that in the serum of other types of ovarian cancer patients.CA125 The expression of serum in patients with ovarian cancer in different stages was significantly different, the higher the expression was, the higher the expression was. (4) the ratio of serum markers, sensitivity, specificity and accuracy in patients with ovarian cancer was higher than that of the single test. The accuracy of the combined detection was higher than that of the single test, but the sensitivity and specificity of the four were combined. There was no difference from the single test, but the combination of HE4+CA125 was significantly higher than the single test in these two aspects, indicating that the combination of the two was low cost, and the accuracy, specificity and sensitivity were the most reasonable.
conclusion
The expression level of 1.VEGF in the ovarian cancer group and in the benign lesion group was significantly higher than that in the normal control group, but the difference in the expression of the ovarian cancer group and the benign lesion group was not obvious, and it could not be used as a single biomarker of ovarian cancer.
There were significant differences in the expression of 2.HE4 in different pathological grades, but there was no significant difference in the expression of VEGF, SMRP, and CA125 three, indicating that it has a good detection value in the pathological classification of ovarian cancer.
The positive rate of 3.CA125 in the ovarian cancer group was significantly higher than that in the benign disease group and the normal control group, and the detection value decreased obviously after one week after the operation and the chemotherapy for four times after 3 weeks of chemotherapy. There was a significant difference between the detection value and the preoperative detection value, and 3 cases of ovarian cancer were positive in the postoperative monitoring and showed an upward trend. After the clinical examination, such as CT, B ultrasound, or postoperative pathological examination. It was found that the recurrence or metastasis of the tumor showed that the expression of.CA125 in the sera of the patients with epithelial ovarian cancer was significantly higher than that of other types of ovarian cancer. It showed that the serum markers of ovarian epithelial tumor were superior to the expression of.CA125 in different stages of ovarian cancer. There is a significant difference. The higher the stage, the higher the expression. It indicates that it plays an important role in the diagnosis, evaluation of curative effect, prognosis and prognosis of ovarian cancer. [3].
4. although the expression of CA125 in the serum of ovarian cancer, especially in patients with epithelial ovarian cancer is obvious, the false positive rate in the benign lesion group is high, so it is necessary to combine with other markers to screen out the most suitable markers and improve the sensitivity, specificity and accuracy of detection. The results suggest that the combination of HE4+CA125 is in combination. These two aspects were significantly higher than the independent tests, indicating that the combination of these two methods was cheap, and the accuracy, specificity and sensitivity were the most reasonable.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.31
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