發(fā)布時(shí)間：2018-06-08 21:15

  本文選題：甲殼質(zhì)酶蛋白40（YKL-40） + 人附睪蛋白4（HE4）��； 參考：《山西醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：通過應(yīng)用酶聯(lián)免疫法（ELISA）檢測血清中人附睪蛋白4（human epididymis protein4,HE4）、 CA125和人類軟骨糖蛋白39(human cartilageglycopmtein,YKL-40)在正常對照組婦女、良性卵巢上皮性腫瘤患者、卵巢上皮性癌患者的表達(dá)水平，探討這三項(xiàng)標(biāo)志物單獨(dú)和聯(lián)合檢測在卵巢上皮性癌中診斷與預(yù)后的臨床價(jià)值。 方法：1.收集在山西省腫瘤醫(yī)院收治的經(jīng)病理診斷確診的上皮性卵巢癌患者40例、40例卵巢良性腫瘤患者術(shù)前血清及同期在山西省腫瘤醫(yī)院體檢中心體檢的40例健康婦女的血清。應(yīng)用酶聯(lián)免疫吸附(Enzyme-linked Immunosorbent Assay，ELISA)雙抗體夾心法檢測血清中HE4、CA125和YKL-40水平，分析比較各組中三項(xiàng)指標(biāo)的水平及上皮性卵巢癌組中Ⅰ/Ⅱ期和Ⅲ/Ⅳ期之間各指標(biāo)的水平，以及觀察上皮性卵巢癌組中患者手術(shù)前后三項(xiàng)指標(biāo)的水平變化。 2.以健康組和上皮性卵巢良性腫瘤組總體作為參考，，分析HE4、CA125和YKL-40診斷卵巢癌的能力，確定血清HE4、CA125和YKL-40最佳界值點(diǎn)。 3.比較血清HE4、CA125和YKL-40單項(xiàng)或聯(lián)合檢測上皮性卵巢癌的敏感度。 4.應(yīng)用SPSS13.0統(tǒng)計(jì)軟件進(jìn)行統(tǒng)計(jì)學(xué)分析。 結(jié)果：1.血清YKL-40在正常對照組婦女、良性卵巢上皮性腫瘤患者、卵巢上皮性癌患者的濃度均數(shù)分別為35.53ng/ml、43.85ng/ml、106.14ng/ml，各組HE4的濃度均數(shù)分別為44.16pmol/L、81.81pmol/L、178.13pmol/L，各組CA125的濃度均數(shù)分別為24.21U/mL、62.75U/mL、242.03U/mL。健康對照組、上皮性良性卵巢腫瘤組及上皮性卵巢癌組血清中的HE4、CA125和YKL-40表達(dá)水平比較：三組血清的HE4、CA125和YKL-40差異均有統(tǒng)計(jì)學(xué)意義（p0.001）,上皮性卵巢癌組血清中三項(xiàng)標(biāo)記物表達(dá)水平都明顯高于健康組和良性組,進(jìn)一步進(jìn)行LSD-t多重比較得，HE4、CA125和YKL-40在卵巢上皮癌組的表達(dá)水平均高于其他兩組（p0.05），HE4和CA125在上皮性良性卵巢腫瘤組的表達(dá)水平均高于健康對照組（p0.05），YKL-40在上皮性良性卵巢腫瘤組與健康對照組的表達(dá)水平差異無統(tǒng)計(jì)學(xué)意義（p0.05）。并且上皮性卵巢癌組中Ⅰ/Ⅱ期與Ⅲ/Ⅳ期中血清HE4、CA125和YKL-40的表達(dá)水平比較：血清HE4水平在Ⅰ/Ⅱ期與Ⅲ/Ⅳ比較差異有統(tǒng)計(jì)學(xué)意義（t7.833,P 0.001），血清CA125水平在Ⅰ/Ⅱ期與Ⅲ/Ⅳ比較差異有統(tǒng)計(jì)學(xué)意義（t12.98， P0.001），血清YKL-40水平在Ⅰ/Ⅱ期與Ⅲ/Ⅳ比較差異有統(tǒng)計(jì)學(xué)意義（t6.786,P 0.001）。 2.上皮性卵巢癌組手術(shù)前后血清HE4、CA125和YKL-40的表達(dá)水平比較：手術(shù)前后血清HE4、CA125和YKL-40的表達(dá)水平差異均有統(tǒng)計(jì)學(xué)意義（p0.05），手術(shù)后血清HE4、CA125和YKL-40的表達(dá)水平均低于手術(shù)前的。 3.以正常對照組+上皮性良性卵巢腫瘤組作參照，分別繪制HE4、CA125和YKL-40的ROC曲線，在（敏感性+特異性）-1取值最大處為其最佳界值點(diǎn)。卵巢癌患者血清中HE4、CA125和YKL-40最佳臨界點(diǎn)，根據(jù)ROC曲線的Youden指數(shù)，可得HE4、CA125、YKL-40的最佳臨界點(diǎn)分別為103.5、95.6、59.975。即在該點(diǎn)它們的診斷價(jià)值最大。 4.血清中HE4、CA125和YKL-40分別以它們的最佳界值點(diǎn)作為陽性標(biāo)準(zhǔn)值范圍，即HE4濃度大于103.5pmol/L時(shí)診斷為陽性，CA125濃度大于95.6U/mL時(shí)診斷為陽性，YKL-40濃度大于59.975ng/mL時(shí)診斷為陽性，單獨(dú)或聯(lián)合檢測血清HE4、CA125和YKL-40水平來評價(jià)診斷上皮性卵巢癌的功效。 5.上皮性卵巢癌患者血清中HE4、CA125和YKL-40靈敏度、特異度比較：三項(xiàng)指標(biāo)聯(lián)合檢測的靈敏度高于單項(xiàng)指標(biāo)，特異度低于單項(xiàng)指標(biāo)，HE4的靈敏度和特異度均較好。 結(jié)論：1.上皮性卵巢癌患者血清中HE4、CA125和YKL-40水平明顯高于上皮性良性腫瘤組和健康對照組水平，然而HE4和CA125在上皮性良性卵巢腫瘤組的表達(dá)水平均高于健康對照組，而YKL-40在上皮性良性卵巢腫瘤組與健康對照組的表達(dá)水平差異無統(tǒng)計(jì)學(xué)意義，提示YKL-40有可能成為卵巢癌篩查的標(biāo)志物。 2．上皮性卵巢癌患者治療前后血清HE4、CA125和YKL-40水平的比較：卵巢癌患者術(shù)后血清HE4、CA125和YKL-40的水平顯著低于術(shù)前的水平,差異具有統(tǒng)計(jì)學(xué)意義。提示上皮性卵巢癌患者術(shù)前血清中HE4、CA125和YKL-40水平有望成為篩查卵巢癌的標(biāo)志物，在卵巢癌的篩查中起到重要作用，因此能協(xié)助卵巢癌的診斷；上皮性卵巢癌患者術(shù)后血清中HE4、CA125和YKL-40水平可能成為卵巢癌臨床手術(shù)療效判斷及術(shù)后病情監(jiān)測的有前景的指標(biāo)。 3.卵巢癌患者血清HE4、CA125和YKL-40檢測的靈敏度分別為92.5%、90%和82.5%,特異性分別為93.8%、95%和95%,三項(xiàng)指標(biāo)聯(lián)合檢測的靈敏度和特異性為97.5%和85%,三項(xiàng)指標(biāo)聯(lián)合檢測的靈敏度高于單項(xiàng)檢測,特異度低于單項(xiàng)指標(biāo),而HE4的靈敏度和特異度均較好。提示聯(lián)合檢測HE4、CA125和YKL-40能夠提高卵巢癌的診斷率，而血清HE4在卵巢癌診斷中有重要意義。
[Abstract]:Objective: to detect the expression levels of human epididymal protein 4 (human epididymis protein4 (HE4), CA125 and human cartilage glycoprotein 39 (human cartilageglycopmtein, YKL-40) in normal control women, benign ovarian epithelial tumor patients and ovarian epithelial cancer patients by enzyme linked immunosorbent assay (ELISA), and explore these three markers. The clinical value of combined detection of single and combined agents in diagnosis and prognosis of epithelial ovarian cancer.
Methods: 1. 40 cases of epithelial ovarian cancer diagnosed by pathological diagnosis in Shanxi cancer hospital were collected, serum of 40 cases of benign ovarian tumors and 40 healthy women in the physical examination center of Shanxi cancer hospital were collected at the same time. Enzyme-linked Immunosorbent Assay (ELISA) double resistance was used. The level of HE4, CA125 and YKL-40 in serum was detected by the body sandwich method. The level of three indexes in each group and the level of each index in the stage I / II and stage III / IV of the epithelial ovarian cancer group were compared and the level of the three indexes before and after the operation in the epithelial ovarian cancer group were observed.
2. the ability of HE4, CA125 and YKL-40 to diagnose ovarian cancer was analyzed with the health group and the epithelial ovarian benign tumor group as a whole. The best boundary value of serum HE4, CA125 and YKL-40 was determined.
3. to compare the sensitivity of serum HE4, CA125 and YKL-40 to detect epithelial ovarian cancer individually or jointly.
4. SPSS13.0 statistical software was used for statistical analysis.
Results: 1. the concentrations of serum YKL-40 in the normal control group, the benign ovarian epithelial tumor and the ovarian epithelial cancer were 35.53ng/ml, 43.85ng/ml, 106.14ng/ml respectively. The concentration of HE4 in each group was 44.16pmol/L, 81.81pmol/L, 178.13pmol/L, and the concentrations of CA125 were 24.21U/mL, 62.75U/mL, and 242.03U/mL. The expression levels of HE4, CA125 and YKL-40 in the serum of the healthy control group, the epithelial ovarian tumor group and the epithelial ovarian cancer group were compared: the differences of serum HE4, CA125 and YKL-40 in the three groups were statistically significant (p0.001). The expression level of the three markers in the serum of the epithelial ovarian cancer group was significantly higher than that in the healthy group and the benign group. The expression level of HE4, CA125 and YKL-40 in the ovarian epithelial cancer group was higher than that of the other two groups (P0.05). The expression level of HE4 and CA125 in the epithelial benign ovarian tumor group was higher than that of the healthy control group (P0.05), and there was no significant difference in the expression level of YKL-40 in the epithelial benign ovarian tumor group and the healthy control group (p0.0, p0.0). 5) and the expression level of serum HE4, CA125 and YKL-40 in stage I / II and stage III / IV of epithelial ovarian cancer group: the level of serum HE4 was statistically significant (t? 7.833, P 0.001) in phase I / II (t? 7.833, P 0.001), and the serum CA125 level was statistically significant (t? 12.98, P0.001) and serum YKL-40 level in stage I / II period (t? 12.98). There was a statistically significant difference between stage I / II and III / IV (t? 6.786, P 0.001).
The expression level of serum HE4, CA125 and YKL-40 before and after operation in 2. epithelial ovarian cancer group: the difference of serum HE4, CA125 and YKL-40 expression level before and after operation was statistically significant (P0.05). The expression level of serum HE4, CA125 and YKL-40 after operation was lower than that before operation.
3. the ROC curves of HE4, CA125 and YKL-40 were plotted in the normal control group and the epithelial benign ovarian tumor group. The optimum boundary point was the maximum value of the (sensitivity + specific) -1 value. The optimal critical point of HE4, CA125 and YKL-40 in the serum of the ovarian cancer patients could be obtained according to the Youden index of the ROC curve, and the best critical points of HE4, CA125 and YKL-40 were obtained. 103.5,95.6,59.975. is the most valuable diagnostic point at this point.
4. HE4, CA125 and YKL-40 were used as positive standard values in their best boundary value points, that is, HE4 was positive when the concentration of HE4 was greater than 103.5pmol/L, and the diagnosis was positive when the concentration of CA125 was greater than 95.6U/mL. The diagnosis was positive when the concentration of YKL-40 was greater than 59.975ng/mL, and the diagnostic value of serum HE4, CA125 and YKL-40 levels was evaluated separately or jointly. The efficacy of skin ovarian cancer.
The sensitivity and specificity of serum HE4, CA125 and YKL-40 in patients with epithelial ovarian cancer were compared: the sensitivity of the combined detection of the three indexes was higher than that of the single index, and the specificity was lower than the single index, and the sensitivity and specificity of HE4 were all better.
Conclusion: the levels of HE4, CA125 and YKL-40 in serum of patients with epithelial ovarian cancer were significantly higher than those in the epithelial benign tumor group and the healthy control group. However, the expression level of HE4 and CA125 in the epithelial benign ovarian tumor group was higher than that in the healthy control group, and the expression level of YKL-40 in the epithelial benign egg nest tumor group and the healthy control group was poor. The difference was not statistically significant, suggesting that YKL-40 may be a marker for ovarian cancer screening.
The comparison of serum HE4, CA125 and YKL-40 levels before and after treatment in patients with epithelial ovarian cancer: the levels of serum HE4, CA125 and YKL-40 in patients with ovarian cancer were significantly lower than those before the operation, and the difference was statistically significant. It is suggested that the serum levels of HE4, CA125 and YKL-40 in the serum of patients with epithelial ovarian cancer are expected to be a sign of screening ovarian cancer before operation. It plays an important role in the screening of ovarian cancer, thus assisting the diagnosis of ovarian cancer. The serum levels of HE4, CA125 and YKL-40 in patients with epithelial ovarian cancer may be a promising indicator of the clinical operation and postoperative monitoring of ovarian cancer.
The sensitivity of serum HE4, CA125, and YKL-40 in patients with ovarian cancer was 92.5%, 90%, and 82.5%, and the specificity was 93.8%, 95% and 95%, respectively. The sensitivity and specificity of the combined detection were 97.5% and 85%, and the sensitivity of the three indexes was higher than the single test, and the specificity was lower than the single index, while the sensitivity and specificity of the HE4 were both. It suggests that combined detection of HE4, CA125 and YKL-40 can improve the diagnostic rate of ovarian cancer. Serum HE4 is of great importance in the diagnosis of ovarian cancer.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R737.31

【參考文獻(xiàn)】

相關(guān)期刊論文 前3條

1 崔恒;;卵巢癌的診治及其研究策略[J];中國婦產(chǎn)科臨床雜志;2006年05期

2 范江濤;李力;;血清甲殼質(zhì)酶蛋白40診治婦科惡性腫瘤研究[J];國際婦產(chǎn)科學(xué)雜志;2008年02期

3 劉潤幸;使用SPSS作多變量觀察值的ROC曲線分析[J];中國公共衛(wèi)生;2003年09期

本文編號(hào)：1997144