發(fā)布時間：2018-04-26 01:25

  本文選題：小分子RNA-96 + 宮頸癌��； 參考：《廣州中醫(yī)藥大學(xué)》2014年碩士論文

【摘要】：目的： 探討小分子RNA-96(microRNA-96, miR-96)在子宮頸癌(Uterine cervical cancer, UCC)組織中的表達情況及其與臨床病理特征之間的關(guān)系；探討新輔助化療對宮頸鱗狀細胞癌組織中miR-96表達的影響,及miR-96的表達變化情況與新輔助化療療效、敏感性、臨床常見的病理特征之間的關(guān)系,以評估其在化療療效及敏感性方面的預(yù)測價值；探討宮頸癌患者組織中miR-96的表達水平與宮頸癌中醫(yī)辨證分型之間的關(guān)系,評價中西醫(yī)結(jié)合治療方法應(yīng)用于宮頸癌臨床治療中的價值和前景。方法： 采用莖環(huán)實時熒光定量聚合酶鏈反應(yīng)技術(shù)(stem-loop quantitative real timePCR,qPCR)測定52例子宮頸惡性腫瘤患者的腫瘤組織、28例宮頸正�；颊叩膶m頸組織中miR-96的表達；同法,檢測28例(Ⅰb2期-Ⅱa期)宮頸鱗狀細胞癌患者新輔助化療前、后腫瘤組織中miR-96的表達；統(tǒng)計分析miR-96的表達水平與臨床病理特征之間的關(guān)系及miR-96的表達變化與新輔助化療的療效、敏感性、臨床病理特征之間的相關(guān)性；運用中醫(yī)辨證分型對宮頸癌組織中miR-96的表達情況進行分析。結(jié)果： 1.52例宮頸癌患者腫瘤組織中miR-96的相對表達量為45.59(15.19,139.61)顯著高于28例正常宮頸組織0.94(0.78,1.11),差異具有統(tǒng)計學(xué)意義(p=0.000)。 2.MiR-96在宮頸癌患者組織中的相對表達量與臨床病理特征(臨床分期,組織學(xué)類型,細胞學(xué)分級,浸潤深度,淋巴結(jié)轉(zhuǎn)移)關(guān)系密切：其在中、低分化癌中的相對表達量61.61(17.74,183.42)顯著高于高分化癌16.78(6.13,66.67),差異有統(tǒng)計學(xué)的意義(p=0.005)；在腺癌中相對表達量為155.67(57.77,270.61),明顯高于鱗癌27.28(13.35,91.00),(p=0.004)；臨床Ⅰ期、Ⅱ期、Ⅲ～Ⅳ期子宮頸癌患者組織中miR-96的相對表達量分別為15.41(7.52,26.26)、85.15(68.32,194.76)462.08(422.57,1028.65),Ⅲ～Ⅳ期顯著高于Ⅰ期、Ⅱ期(p=0.000、p=0.001),Ⅱ期顯著高于Ⅰ期,且差異均具有統(tǒng)計學(xué)的意義(P=0.000)；淋巴結(jié)有轉(zhuǎn)移組的相對表達量為163.46(28.95,205.62)明顯高于無淋巴結(jié)轉(zhuǎn)移組14.16(6.99,22.61),(p=0.000)；浸潤深度：≥1/2間質(zhì)的相對表達量為24.72(14.44,141.79),顯著高于1/2間質(zhì)者13.79(5.14,25.649),(p=0.025)；而與患者年齡無明顯關(guān)系(p=0.385)。 3.28例宮頸鱗狀細胞癌患者新輔助化療后miR-96的表達水平明顯下降；新輔助化療前宮頸癌腫瘤組織中miR-96的相對表達量是化療后腫瘤組織中的3.40(2.01,6.86)倍,差異具有統(tǒng)計學(xué)的意義(p=0.000)。 4.宮頸鱗狀細胞癌患者新輔助化療前、后腫瘤組織中miR-96表達變化的相對定量結(jié)果與臨床病理特征之間關(guān)系密切：細胞分化程度為中、低分化者2.51(1.21,33.26)低于高分化者8.22(5.21,15.39)(p=0.000)；間質(zhì)浸潤深度1/2間質(zhì)者5.66(4.06,14.09)明顯高于浸潤深度≥1/2間質(zhì)者1.91(0.90,2.96)(p=0.000)；有淋巴結(jié)轉(zhuǎn)移者1.79(0.86,2.64)明顯低于無淋巴轉(zhuǎn)移者5.43(4.04,12.84)(p=0.000)；而年齡≤45歲、45歲,臨床分期為Ⅰb2期、Ⅱa期患者,化療前后miR-96表達變化均沒有統(tǒng)計學(xué)差異(p0.05)。 5.新輔助化療有效組(CR+PR)同無效組(SD+PD)相比較：有效組化療后腫瘤組織中的miR-96表達水平明顯下降(p=0.000),無效組化療前、后腫瘤組織中miR-96的表達水平變化無統(tǒng)計學(xué)差異(p0.05)；新輔助化療前有效組腫瘤組織中miR-96的表達水平明顯低于無效組(p=0.001),新輔助化療后有效組腫瘤組織中miR-96的表達水平也明顯低于無效組(p=0.001)。 6.宮頸鱗狀細胞癌患者行新輔助化療前腫瘤組織中miR-96的相對表達量與三維超聲參數(shù)血流指數(shù)(FI)、血管形成指數(shù)(VI)、血管血流指數(shù)(VFI)、化療后殘余腫瘤體積百分比呈明顯正相關(guān)(p0.05),而與化療前腫瘤體積無明顯相關(guān)性(p0.05)。 7.宮頸癌患者組織中miR-96的表達水平與中醫(yī)辨證分型之間的關(guān)系：肝腎陰虛、脾腎陽虛型患者腫瘤組織中miR-96的表達水平明顯高于肝郁氣滯型、濕熱瘀毒型,差異有統(tǒng)計學(xué)的意義(p0.05)；而脾腎陽虛型與肝腎陰虛型患者腫瘤組織中miR-96的表達,肝郁氣滯型與濕熱瘀毒型患者腫瘤織中miR-96的表達均無統(tǒng)計學(xué)差異(p0.05)。結(jié)論： 1.MiR-96在宮頸癌組織中異常高表達,其表達水平與患者臨床病理特征之間關(guān)系密切,提示其可能在宮頸癌的發(fā)生發(fā)展中發(fā)揮致癌基因的作用,并且與宮頸癌的演進及不良預(yù)后密切相關(guān)。 2.新輔助化療能有效降低miR-96在子宮頸惡性腫瘤組織中的表達,化療前腫瘤組織中miR-96的表達水平與化療的敏感性、臨床療效關(guān)系密切,因此測定化療前宮頸癌組織中miR-96的表達水平對新輔助化療療效及敏感性預(yù)測具有一定參考價值。 3.宮頸癌患者腫瘤組織中miR-96的表達水平與中醫(yī)辨證分型密切相關(guān)：脾腎陽虛型、肝腎陰虛證型中的表達水平明顯高于肝郁氣滯型、濕熱瘀毒證型。
[Abstract]:Objective:
To investigate the expression of small molecule RNA-96 (microRNA-96, miR-96) in the tissues of Uterine cervical cancer (UCC) and its relationship with the clinicopathological features, and to explore the effect of neoadjuvant chemotherapy on the expression of miR-96 in cervical squamous cell carcinoma, and the changes in the expression of miR-96 and the efficacy and sensitivity of the neoadjuvant chemotherapy. The relationship between the common pathological features of the clinic to evaluate the predictive value of the therapeutic effect and sensitivity in chemotherapy, the relationship between the expression of miR-96 in the tissues of cervical cancer patients and the TCM syndrome differentiation of cervical cancer, and to evaluate the value and Prospect of the combination of traditional Chinese and Western medicine in the clinical treatment of cervical cancer.
Stem-loop quantitative real timePCR (qPCR) was used to determine the expression of miR-96 in 52 cases of cervical malignant tumor, 28 cases of cervical normal patients and 28 cases of cervical squamous cell carcinoma (I B2 phase II a phase) before and after neoadjuvant chemotherapy and posterior swelling in 28 cases of cervical squamous cell carcinoma. The expression of miR-96 in the tumor tissue; statistical analysis of the relationship between the expression level of miR-96 and the clinicopathological features and the correlation between the expression of miR-96 and the curative effect, sensitivity and clinicopathological features of the neoadjuvant chemotherapy, and the analysis of the expression of miR-96 in cervical cancer by TCM syndrome differentiation.
The relative expression of miR-96 in the tumor tissues of 1.52 patients with cervical cancer was 45.59 (15.19139.61) significantly higher than that in 28 cases of normal cervical tissue (0.78,1.11), and the difference was statistically significant (p=0.000).
The relative expression of 2.MiR-96 in the tissues of patients with cervical cancer was closely related to the clinicopathological features (clinical stage, histological type, cytological classification, infiltration depth, lymph node metastasis). In the middle, the relative expression of 61.61 (17.74183.42) in the low differentiated carcinoma was significantly higher than that of the highly differentiated carcinoma (6.13,66.67), and the difference was statistically significant (p=0 The relative expression of.005 in adenocarcinoma was 155.67 (57.77270.61), which was significantly higher than that of squamous carcinoma (13.35,91.00), (p=0.004). The relative expression of miR-96 in the tissues of patients with stage I, stage II, and stage III to IV of cervical cancer was 15.41 (7.52,26.26), 85.15 (68.32194.76) 462.08 (422.571028.65) and stage III to IV significantly higher than stage I, stage II (P). =0.000, p=0.001), the stage II was significantly higher than phase I, and the difference was statistically significant (P=0.000), the relative expression of the lymph node metastasis group was 163.46 (28.95205.62) significantly higher than that in the non lymph node group (6.99,22.61), (p=0.000), and the infiltration depth was 24.72 (14.44141.79), which was significantly higher than that of 1/2 (14.44141.79). The interstitial mass was 13.79 (5.14,25.649), (p=0.025), but not significantly related to the age of the patients (p=0.385).
The expression level of miR-96 in 3.28 cases of cervical squamous cell carcinoma was significantly decreased after neoadjuvant chemotherapy, and the relative expression of miR-96 in cervical cancer tissues before neoadjuvant chemotherapy was 3.40 (2.01,6.86) times of the tumor tissue after chemotherapy, and the difference was statistically significant (p=0.000).
4. before the neoadjuvant chemotherapy of cervical squamous cell carcinoma, the relative quantitative results of miR-96 expression in the posterior tumor tissues were closely related to the clinicopathological features: the degree of cell differentiation was in the middle, the low differentiation 2.51 (1.21,33.26) was 8.22 (5.21,15.39) lower than that of the high differentiation (p= 0), and the interstitial infiltrating depth of the interstitial 1/2 was 5.66 (4.06,14.09). 1.91 (0.90,2.96) (p=0.000) and 1.79 (0.86,2.64) with lymph node metastases were significantly lower than those of 1/2 (0.86,2.64) with lymph node metastases, and 5.43 (4.04,12.84) (p=0.000) were lower than those without lymphatic metastasis, while the age was less than 45 years and 45 years old, and the clinical stage was I B2 stage, and there was no statistical difference in the changes of miR-96 expression in the patients with stage II a (P0.05).
5. the effective group of neoadjuvant chemotherapy (CR+PR) was compared with the ineffective group (SD+PD): the expression level of miR-96 in the tumor tissues of the effective group decreased significantly (p=0.000). There was no significant difference in the expression of miR-96 in the tumor tissues (P0.05) before chemotherapy (P0.05); the expression level of miR-96 in the tumor tissues before the neoadjuvant chemotherapy was clear. The expression level of miR-96 in the effective group after neoadjuvant chemotherapy was significantly lower than that in the ineffective group (p=0.001), which was significantly lower than that in the ineffective group (p=0.001).
6. the relative expression of miR-96 in the tumor tissue of the cervical squamous cell carcinoma patients before the neoadjuvant chemotherapy and the three dimensional ultrasound parameter blood index (FI), the angiogenic index (VI), the blood vessel blood flow index (VFI), the percentage of the residual tumor volume after chemotherapy (P0.05), and no significant correlation with the tumor volume before chemotherapy (P0.05).
7. the relationship between the expression level of miR-96 in the tissues of the patients with cervical cancer and the syndrome differentiation of traditional Chinese medicine: the expression level of miR-96 in the tumor tissues of the patients with spleen and kidney yang deficiency is significantly higher than that of the liver qi stagnation, and the difference is statistically significant (P0.05), while the spleen kidney yang deficiency and the liver kidney yin deficiency patients are in the tumor tissue of miR-9. 6, there was no significant difference in the expression of miR-96 in tumor tissue between liver qi stagnation type and damp heat stasis type (P0.05).
1.MiR-96 is highly expressed in cervical cancer, and its expression level is closely related to the clinicopathological features of the patients, suggesting that it may play the role of the oncogene in the development of cervical cancer, and is closely related to the evolution and poor prognosis of cervical cancer.
2. neoadjuvant chemotherapy can effectively reduce the expression of miR-96 in the malignant tumor tissues of the cervix. The expression of miR-96 in the tumor tissue before chemotherapy is closely related to the sensitivity of chemotherapy and the clinical efficacy. Therefore, the determination of the expression level of miR-96 in the cervical cancer tissues before chemotherapy is of reference value for the therapeutic effect and sensitivity prediction of the neoadjuvant therapy.
3. the expression level of miR-96 in the tumor tissues of the patients with cervical cancer is closely related to the TCM syndrome differentiation: the expression level in the spleen kidney yang deficiency type, the liver kidney yin deficiency syndrome type is obviously higher than the liver qi stagnation type, the damp heat stasis syndrome type.

【學(xué)位授予單位】：廣州中醫(yī)藥大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R737.33

【參考文獻】

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本文編號：1803869