VEGF、SMRP、HE4及CA125的檢測(cè)在卵巢癌診治監(jiān)測(cè)中的價(jià)值
發(fā)布時(shí)間：2018-07-25 08:52
【摘要】：卵巢癌在是臨床婦科常見的惡性腫瘤，其發(fā)病率高，在女性惡性腫瘤中占2.4%～5.6%，因其深居盆腔，早期無特異癥狀，約60～70%患者發(fā)現(xiàn)時(shí)已屬晚期，所以早期診斷困難；即使有效治療，仍有70%左右患者在緩解后復(fù)發(fā)。死亡率一直居女性生殖道腫瘤的第一位[1]。據(jù)統(tǒng)計(jì)資料表明，I～I(xiàn)I期卵巢癌經(jīng)手術(shù)化療后5年生存率可以達(dá)到80~95%,而III～I(xiàn)V期僅為20～30%[2]。所以早發(fā)現(xiàn)、早診斷、早治療及術(shù)后療效監(jiān)測(cè)是提高患者生存率的關(guān)鍵，腫瘤標(biāo)志物的檢測(cè)在其診治中有著非常重要的意義，多數(shù)學(xué)者主張采用聯(lián)合檢測(cè)腫瘤標(biāo)志物的方法，可彌補(bǔ)單項(xiàng)檢測(cè)的不足，有助于提高腫瘤檢出率。 目的研究顯示卵巢腫瘤發(fā)病率有逐年上升的趨勢(shì)，每年因卵巢癌致死的患者在各類女性生殖器惡性腫瘤患者中占據(jù)第一位。所以對(duì)于卵巢癌的診斷和積極治療是有著很重要的意義的。從分子水平上探索卵巢癌的發(fā)生機(jī)制，是近些年來研究的熱點(diǎn)。正是因?yàn)槟承┥飿?biāo)志物在人體病變中表達(dá)率異常，所以可選其進(jìn)行檢驗(yàn)，以此來判斷病變的可能、進(jìn)展以及據(jù)此制定治療方案等。本研究運(yùn)用血管內(nèi)皮細(xì)胞生長(zhǎng)因子(VEGF)、血清間皮素相關(guān)蛋白（SMRP）、人類附睪蛋白4（HE4）和跨膜糖蛋白(CA125)的檢測(cè)，觀察四者在卵巢癌診治中的作用，為診斷和治療該病提供一定的理論依據(jù)。 方法收集靖江市人民醫(yī)院2010年1月到2013年12月卵巢癌患者、良性卵巢病變患者（后均經(jīng)過病理確診）以及正常體檢者的血清進(jìn)行檢測(cè)，對(duì)其檢測(cè)結(jié)果進(jìn)行回顧性分析，這三組患者分為卵巢癌組、卵巢良性病變組和正常對(duì)照組。采集受試者空腹靜脈血5mL，離心后上清液置入-80攝氏度冰箱保存，5天內(nèi)檢測(cè)；運(yùn)用瑞典康乃格公司生產(chǎn)的相關(guān)試劑盒進(jìn)行腫瘤標(biāo)志物血管內(nèi)皮細(xì)胞生長(zhǎng)因子(VEGF)、血清間皮素相關(guān)蛋白（SMRP）、人附睪蛋白4（HE4）的測(cè)定，用化學(xué)發(fā)光法測(cè)定CA125；研究數(shù)據(jù)統(tǒng)計(jì)學(xué)處理采用SPSS19.0進(jìn)行統(tǒng)計(jì)分析。組間樣本用χ2檢驗(yàn)；數(shù)據(jù)符合正態(tài)性，方差齊性時(shí)采用t檢驗(yàn)進(jìn)行統(tǒng)計(jì)分析，如不符合正態(tài)分布，則用Wilcoxon秩和檢驗(yàn)進(jìn)行統(tǒng)計(jì)分析。 結(jié)果（1）VEGF在卵巢癌組中的表達(dá)水平為238.14±17.32pg/L，在良性病變組的表達(dá)水平為189.32±16.38pg/L，均顯著高于正常對(duì)照組的110.68±12.28pg/L(P0.05)。而在卵巢癌組和良性病變組中的表達(dá)差異不明顯，無統(tǒng)計(jì)學(xué)意義(P0.05)。SMRP在觀察組的表達(dá)明顯高于其他兩組，有統(tǒng)計(jì)學(xué)意義(P0.05)；在良性病變組和正常對(duì)照組中的表達(dá)無明顯差異(P0.05)。HE4在卵巢癌組中的表達(dá)明顯高于其他兩組，而在正常對(duì)照組和良性病變組中的表達(dá)差異不明顯，無統(tǒng)計(jì)學(xué)意義(P0.05)；CA125在正常對(duì)照組的表達(dá)非常低，在卵巢癌組中的表達(dá)與良性病變組相比，有明顯差異；CA125在卵巢癌組的陽性率(73.0%)顯著高于良性病變組(19.0%)和正常對(duì)照(2.0%)(P0.05)，但是良性病變組的假陽性率極高，明顯高于其他兩組(P0.05)。（2）卵巢癌患者CA125的檢測(cè)值在術(shù)后以及化療四周后明顯下降，與術(shù)前檢測(cè)值有明顯差異（P0.05），VEGF、SMRP、HE4的檢測(cè)值在術(shù)后以及化療四周后也有下降，但是三個(gè)時(shí)間點(diǎn)的檢測(cè)值相比，并無明顯差異（P0.05）。有3例卵巢癌術(shù)后監(jiān)測(cè)中出現(xiàn)陽性并呈上升趨勢(shì)，后經(jīng)臨床檢查如CT，B超或手術(shù)后病理檢測(cè)確定為腫瘤復(fù)發(fā)或發(fā)生轉(zhuǎn)移；（3）在不同病理分級(jí)中，由高分化癌到中分化癌再到低分化癌，HE4的表達(dá)逐漸升高，并且統(tǒng)計(jì)學(xué)有明顯差異（P0.05），而VEGF、SMRP、CA125三者的表達(dá)均未見明顯差異（P0.05）；而在不同分期及分型的卵巢癌患者中，其血清HE4的表達(dá)無明顯差異。VEGF在不同類型不同分期不同分級(jí)的卵巢癌患者血清中的表達(dá)無明顯差異，而SMRP、CA125在卵巢上皮性腫瘤患者血清中的表達(dá)與其他類型卵巢癌患者血清中的表達(dá)相比有明顯差異。CA125在不同分期的卵巢癌患者血清中的表達(dá)有明顯差異，分期越晚，表達(dá)越高。（4）單獨(dú)或是聯(lián)合檢測(cè)卵巢癌患者中的血清標(biāo)志物含量，敏感性、特異性和準(zhǔn)確度比較，聯(lián)合檢測(cè)的準(zhǔn)確率均高于單獨(dú)檢測(cè)，但是在敏感性和特異性方面，四者聯(lián)合檢測(cè)與單獨(dú)檢測(cè)并無差異，而HE4+CA125聯(lián)合則在這兩方面均顯著高于單獨(dú)檢測(cè)，說明這兩者聯(lián)合的成本低廉，且準(zhǔn)確度，特異性和敏感性均最合理。 結(jié)論 1.VEGF在卵巢癌組中和在良性病變組的表達(dá)水平均顯著高于正常對(duì)照組。而在卵巢癌組和良性病變組中的表達(dá)差異不明顯，其無法作為卵巢癌的單一生物標(biāo)志物。 2.HE4在不同病理分級(jí)中，表達(dá)有明顯差異，而VEGF、SMRP、CA125三者的表達(dá)均未見明顯差異，說明其在卵巢癌的病理分級(jí)中有著較好的檢測(cè)價(jià)值。 3.CA125在卵巢癌組的陽性率顯著高于良性病變組和正常對(duì)照組，且檢測(cè)值在術(shù)后一周以及化療3周化療四次后明顯下降，與術(shù)前檢測(cè)值有明顯差異，且有3例卵巢癌術(shù)后監(jiān)測(cè)中出現(xiàn)陽性并呈上升趨勢(shì)，后經(jīng)臨床檢查如CT，B超或手術(shù)后病理檢測(cè)認(rèn)定為腫瘤復(fù)發(fā)或發(fā)生轉(zhuǎn)移，說明其在卵巢癌術(shù)后監(jiān)測(cè)預(yù)知復(fù)發(fā)方面有意義。CA125在上皮性卵巢癌患者血清中的表達(dá)明顯高于其他類型卵巢癌，說明其作為卵巢上皮性腫瘤的血清標(biāo)志物檢測(cè)優(yōu)越性明顯。CA125在卵巢癌不同分期的表達(dá)有明顯差異，分期越晚，表達(dá)越高。說明其在卵巢癌的診斷、評(píng)估療效、估計(jì)復(fù)發(fā)與預(yù)后方面發(fā)揮了重要的作用[3]。 4.雖然CA125在卵巢癌尤其是上皮性卵巢癌患者血清中的表達(dá)很明顯，但其在良性病變組檢測(cè)中的假陽性率較高，所以需要與其他標(biāo)志物進(jìn)行聯(lián)合，以篩選出最為合適的標(biāo)志物，，提高敏感性、特異性和檢測(cè)準(zhǔn)確性，結(jié)果提示HE4+CA125聯(lián)合則在這兩方面均顯著高于單獨(dú)檢測(cè)，說明這兩者聯(lián)合的成本低廉，且準(zhǔn)確度，特異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.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：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.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R737.31
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相關(guān)期刊論文 前10條
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