P16、OLFM4在宮頸上皮內(nèi)瘤變中的表達(dá)及其診斷意義
發(fā)布時(shí)間：2018-08-03 21:38
【摘要】：在世界上,宮頸癌被認(rèn)為是女性惡性腫瘤中最常見(jiàn)的疾病之一,僅次于乳腺癌,但宮頸癌是唯一能夠早期預(yù)防和早期診斷的惡性腫瘤。宮頸上皮內(nèi)瘤變(Cervical Intraepithelial Neoplasia,CIN)是宮頸癌前病變的主要疾病狀態(tài),對(duì)宮頸癌的發(fā)生具有重要的推動(dòng)作用。為了降低宮頸癌的發(fā)生率和死亡率,改善預(yù)后,如果臨床醫(yī)生能夠針對(duì)癌前狀態(tài)及時(shí)給予干擾及阻斷,將病灶完全清除,對(duì)宮頸癌的防治有重要意義。因此,在宮頸病變的篩查中,生物標(biāo)志物作為一種特異性物質(zhì)已經(jīng)逐漸地被應(yīng)用,這會(huì)對(duì)宮頸癌的預(yù)防和治療會(huì)起到重要的作用。P16INK4A基因是一種抑癌基因,即人類周期素依賴性激酶(cyclin dependent kinase,CDK)4抑制因子(p16)基因,它所表達(dá)蛋白的是一種抑癌蛋白,即P16蛋白。在宮頸病變中,P16INK4A的表達(dá)隨著宮頸病變程度的增加而升高。人類嗅素蛋白4(olfactomedin4,OLFM4)是一種新的抗凋亡蛋白,可促進(jìn)腫瘤細(xì)胞的生長(zhǎng),同時(shí)能準(zhǔn)確地反映宮頸上皮細(xì)胞的增殖和分化情況,能夠很好地區(qū)分正常宮頸組織與宮頸上皮內(nèi)瘤變(CIN),如果將這兩種生物標(biāo)志物聯(lián)合檢測(cè)能更好地輔助宮頸病變的診斷,預(yù)測(cè)宮頸病變級(jí)別及進(jìn)展,從而降低患者的經(jīng)濟(jì)支出,進(jìn)而也減輕患者的精神負(fù)擔(dān)。研究對(duì)象是2015至2016年曾因?qū)m頸病變就診于河北北方學(xué)院附屬第一醫(yī)院婦科門診,并于婦科門診手術(shù)室行陰道鏡下宮頸活檢術(shù)的病理標(biāo)本,年齡范圍為21-68歲。實(shí)驗(yàn)組是陰道鏡下宮頸活檢病理診斷結(jié)果為宮頸上皮內(nèi)瘤變(CIN)的病理標(biāo)本,并依據(jù)組織學(xué)診斷結(jié)果將其分為三個(gè)亞組,其中宮頸上皮內(nèi)瘤變I級(jí)(cervical intraepithelial neoplasia grade 1,CINI)50例,宮頸上皮內(nèi)瘤變II級(jí)(cervical intraepithelial neoplasia grade 2,CINII)50例,宮頸上皮內(nèi)瘤變III級(jí)(cervical intraepithelial neoplasia grade3,CINIII)50例。陰道鏡宮頸活檢術(shù)均由�？漆t(yī)生操作,正常對(duì)照組30例是因子宮良性病變切除子宮的病理標(biāo)本。采用免疫組織化學(xué)法(immunohistochemistry,IHC)對(duì)其病理標(biāo)本進(jìn)行檢測(cè)。實(shí)驗(yàn)組中P16和OLFM4的陽(yáng)性表達(dá)率分別為88.67%、87.33%,而對(duì)照組中P16和OLFM4的陽(yáng)性表達(dá)率分別為26.67%、20.00%。實(shí)驗(yàn)組均高于對(duì)照組,所以,P16的陽(yáng)性表達(dá)率具有顯著的統(tǒng)計(jì)學(xué)差異(χ2=58.463,P0.05),OLFM4的陽(yáng)性表達(dá)率具有顯著的統(tǒng)計(jì)學(xué)差異(χ2=63.459,P0.05)。P16在實(shí)驗(yàn)組(CINI、CINII、CINIII)中陽(yáng)性表達(dá)率分別為76.00%、90.00%和100.00%,有顯著性差異(χ2=112.582,P0.05),每?jī)山M間比較P16的表達(dá)均有統(tǒng)計(jì)學(xué)差異(P0.05)。OLFM4在實(shí)驗(yàn)組(CINI、CINII、CINIII)中陽(yáng)性表達(dá)率分別為76.00%、86.00%和100.00%,有統(tǒng)計(jì)學(xué)差異(χ2=124.866,P0.05),且每?jī)山M間比較OLFM4的表達(dá)均有統(tǒng)計(jì)學(xué)意義(P0.05)�？傊�,CINIII組陽(yáng)性表達(dá)率最高、其次是CINII組陽(yáng)性表達(dá)率、CINI組陽(yáng)性表達(dá)率最低。從以上數(shù)據(jù)分析,P16的表達(dá)陽(yáng)性率與宮頸上皮內(nèi)瘤變(CIN)病變程度有顯著的相關(guān)性(r=0.613,P0.05),OLFM4的表達(dá)陽(yáng)性率與宮頸上皮內(nèi)瘤變(CIN)病變程度也有顯著的相關(guān)性(r=0.380,P0.05),可知,宮頸上皮內(nèi)瘤變(CIN)病變程度越嚴(yán)重,P16和OLFM4陽(yáng)性表達(dá)率越高。從實(shí)驗(yàn)組P16和OLFM4表達(dá)情況相關(guān)性分析可知,P16和OLFM4的表達(dá)也存在相關(guān)性,P16的陽(yáng)性表達(dá)率越高,則OLFM4的陽(yáng)性表達(dá)率也隨之增高。根據(jù)spearman相關(guān)分析,P16和OLFM4的聯(lián)合表達(dá)情況與宮頸病變程度有顯著性的相關(guān)(r=0.862,P0.05)。P16和OLFM4聯(lián)合表達(dá)率在CINI、CINII、CINIII各組中為0、70.00%、100%,P16和OLFM4聯(lián)合表達(dá)率越高,宮頸病變程度越高。綜上所述,P16、OLFM4的表達(dá)與宮頸上皮內(nèi)瘤變(CIN)的嚴(yán)重程度呈正向關(guān)系。并且,P16、OLFM4的高表達(dá)與宮頸上皮內(nèi)瘤變(CIN)臨床分級(jí)呈正向相關(guān)關(guān)系,將有助于提高對(duì)宮頸上皮內(nèi)瘤變(CIN)診斷的一致性,從而更好地診斷和預(yù)防宮頸上皮內(nèi)瘤變(CIN)。同時(shí),P16、OLFM4聯(lián)合表達(dá)率隨宮頸病變程度的加重而升高,其聯(lián)合檢測(cè)為宮頸癌的篩查的分流管理,疾病的早期診斷及治療,尤其是可以更好地分流CINII,從而提供個(gè)體化診療方案非常重要。
[Abstract]:In the world, cervical cancer is considered to be one of the most common diseases in female malignant tumors, second only to breast cancer, but cervical cancer is the only malignant tumor that can be prevented early and early diagnosis. Cervical intraepithelial neoplasia (Cervical Intraepithelial Neoplasia, CIN) is the main disease state of precancerous lesions of the cervix and the occurrence of cervical cancer. In order to reduce the incidence and mortality of cervical cancer and improve the prognosis, it is of great significance for the prevention and control of cervical cancer if the clinician can give timely interference and interruption to the precancerous condition, and it is of great significance for the prevention and treatment of cervical cancer. Gradually applied, this will play an important role in the prevention and treatment of cervical cancer. The.P16INK4A gene is a tumor suppressor gene, the cyclin dependent kinase (CDK) 4 inhibitory factor (p16) gene, which expresses a tumor suppressor white egg white, that is, the P16 protein. In cervical lesions, P16INK4A expression along with the expression of P16INK4A Human olfactory protein 4 (olfactomedin4, OLFM4) is a new anti apoptotic protein, which can promote the growth of tumor cells, and can accurately reflect the proliferation and differentiation of cervical epithelial cells. It can be well divided into normal cervical and cervical intraepithelial neoplasia (CIN), if these two species are to be used. Combined detection of markers can better assist the diagnosis of cervical lesions, predict the level and progress of cervical lesions, thus reduce the economic expenditure of the patients, and then reduce the mental burden of the patients. The study was from 2015 to 2016 in the gynecologic outpatient of First Affiliated Hospital of Hebei North University because of cervical lesions, and in the operation room of gynecologic outpatient department. The pathological specimen of cervical biopsy under colposcopy was 21-68 years old. The experimental group was a pathological specimen of cervical intraepithelial neoplasia (CIN) of cervical biopsy under colposcopy, and was divided into three subgroups according to the histological diagnosis, of which the cervical intraepithelial neoplasia was I (cervical intraepithelial neoplasia grade 1,) CINI) 50 cases, cervical intraepithelial neoplasia (cervical intraepithelial neoplasia grade 2, CINII) in 50 cases, cervical intraepithelial neoplasia III grade (cervical intraepithelial neoplasia Grade3,) 50 cases. Colposcopy cervical biopsy was operated by a specialist, and 30 cases of the normal group were pathological specimens of the uterus due to benign uterine lesions. The positive expression rate of P16 and OLFM4 in the experimental group was 88.67%, 87.33%, respectively, and the positive expression rate of P16 and OLFM4 in the control group was 26.67%, respectively, and the 20.00%. experimental group was higher than the control group. Therefore, the positive expression rate of P16 was statistically significant difference. The positive expression rate of OLFM4 was significantly different (x 2=63.459, P0.05).P16 in the experimental group (CINI, CINII, CINIII) in the experimental group (CINI, CINII, CINIII) was 76%, 90% and 100%, respectively (chi, 2=112.582, P0.05), and there were significant differences in the expression of P16 in the two groups. The positive expression rate in CINII, CINIII) was 76%, 86% and 100% respectively (x 2=124.866, P0.05), and the expression of OLFM4 in each two groups was statistically significant (P0.05). In a word, the positive rate of CINIII group was the highest, followed by the positive rate of CINII group, and the lowest positive rate in the CINI group. From the above data analysis, the P16 table There was a significant correlation between the positive rate and the degree of cervical intraepithelial neoplasia (CIN) (r=0.613, P0.05). The positive rate of OLFM4 expression was also significantly correlated with the degree of cervical intraepithelial neoplasia (CIN) (r=0.380, P0.05). It is known that the more serious the cervical intraepithelial neoplasia (CIN), the higher the positive expression rate of P16 and OLFM4. From experimental group P16. The correlation analysis of the expression of OLFM4 showed that the expression of P16 and OLFM4 also existed, the higher the positive expression rate of P16, the positive expression rate of OLFM4 increased. According to the Spearman correlation analysis, the joint expression of P16 and OLFM4 had a significant correlation with the degree of cervical lesions (r=0.862, P0.05).P16 and OLFM4 joint expression rate The higher the combined expression rate of 0,70.00%, 100%, P16 and OLFM4 in NI, CINII, and CINIII, the higher the degree of cervical lesions. To sum up, the expression of P16, OLFM4 has a positive relationship with the severity of cervical intraepithelial neoplasia (CIN). Moreover, the high expression of P16, OLFM4 is positively related to the clinical classification of cervical intraepithelial neoplasia (CIN), and will help to improve The diagnosis and prevention of cervical intraepithelial neoplasia (CIN) is consistent to better diagnose and prevent cervical intraepithelial neoplasia (CIN). At the same time, the combined expression rate of P16 and OLFM4 increases with the aggravation of the degree of cervical lesions, which is combined to detect the shunt management of cervical cancer screening, early diagnosis and treatment of the disease, especially to divert CINII better. It is very important to provide an individualized diagnosis and treatment scheme.
【學(xué)位授予單位】：河北北方學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R737.33
本文編號(hào)：2163068
[Abstract]:In the world, cervical cancer is considered to be one of the most common diseases in female malignant tumors, second only to breast cancer, but cervical cancer is the only malignant tumor that can be prevented early and early diagnosis. Cervical intraepithelial neoplasia (Cervical Intraepithelial Neoplasia, CIN) is the main disease state of precancerous lesions of the cervix and the occurrence of cervical cancer. In order to reduce the incidence and mortality of cervical cancer and improve the prognosis, it is of great significance for the prevention and control of cervical cancer if the clinician can give timely interference and interruption to the precancerous condition, and it is of great significance for the prevention and treatment of cervical cancer. Gradually applied, this will play an important role in the prevention and treatment of cervical cancer. The.P16INK4A gene is a tumor suppressor gene, the cyclin dependent kinase (CDK) 4 inhibitory factor (p16) gene, which expresses a tumor suppressor white egg white, that is, the P16 protein. In cervical lesions, P16INK4A expression along with the expression of P16INK4A Human olfactory protein 4 (olfactomedin4, OLFM4) is a new anti apoptotic protein, which can promote the growth of tumor cells, and can accurately reflect the proliferation and differentiation of cervical epithelial cells. It can be well divided into normal cervical and cervical intraepithelial neoplasia (CIN), if these two species are to be used. Combined detection of markers can better assist the diagnosis of cervical lesions, predict the level and progress of cervical lesions, thus reduce the economic expenditure of the patients, and then reduce the mental burden of the patients. The study was from 2015 to 2016 in the gynecologic outpatient of First Affiliated Hospital of Hebei North University because of cervical lesions, and in the operation room of gynecologic outpatient department. The pathological specimen of cervical biopsy under colposcopy was 21-68 years old. The experimental group was a pathological specimen of cervical intraepithelial neoplasia (CIN) of cervical biopsy under colposcopy, and was divided into three subgroups according to the histological diagnosis, of which the cervical intraepithelial neoplasia was I (cervical intraepithelial neoplasia grade 1,) CINI) 50 cases, cervical intraepithelial neoplasia (cervical intraepithelial neoplasia grade 2, CINII) in 50 cases, cervical intraepithelial neoplasia III grade (cervical intraepithelial neoplasia Grade3,) 50 cases. Colposcopy cervical biopsy was operated by a specialist, and 30 cases of the normal group were pathological specimens of the uterus due to benign uterine lesions. The positive expression rate of P16 and OLFM4 in the experimental group was 88.67%, 87.33%, respectively, and the positive expression rate of P16 and OLFM4 in the control group was 26.67%, respectively, and the 20.00%. experimental group was higher than the control group. Therefore, the positive expression rate of P16 was statistically significant difference. The positive expression rate of OLFM4 was significantly different (x 2=63.459, P0.05).P16 in the experimental group (CINI, CINII, CINIII) in the experimental group (CINI, CINII, CINIII) was 76%, 90% and 100%, respectively (chi, 2=112.582, P0.05), and there were significant differences in the expression of P16 in the two groups. The positive expression rate in CINII, CINIII) was 76%, 86% and 100% respectively (x 2=124.866, P0.05), and the expression of OLFM4 in each two groups was statistically significant (P0.05). In a word, the positive rate of CINIII group was the highest, followed by the positive rate of CINII group, and the lowest positive rate in the CINI group. From the above data analysis, the P16 table There was a significant correlation between the positive rate and the degree of cervical intraepithelial neoplasia (CIN) (r=0.613, P0.05). The positive rate of OLFM4 expression was also significantly correlated with the degree of cervical intraepithelial neoplasia (CIN) (r=0.380, P0.05). It is known that the more serious the cervical intraepithelial neoplasia (CIN), the higher the positive expression rate of P16 and OLFM4. From experimental group P16. The correlation analysis of the expression of OLFM4 showed that the expression of P16 and OLFM4 also existed, the higher the positive expression rate of P16, the positive expression rate of OLFM4 increased. According to the Spearman correlation analysis, the joint expression of P16 and OLFM4 had a significant correlation with the degree of cervical lesions (r=0.862, P0.05).P16 and OLFM4 joint expression rate The higher the combined expression rate of 0,70.00%, 100%, P16 and OLFM4 in NI, CINII, and CINIII, the higher the degree of cervical lesions. To sum up, the expression of P16, OLFM4 has a positive relationship with the severity of cervical intraepithelial neoplasia (CIN). Moreover, the high expression of P16, OLFM4 is positively related to the clinical classification of cervical intraepithelial neoplasia (CIN), and will help to improve The diagnosis and prevention of cervical intraepithelial neoplasia (CIN) is consistent to better diagnose and prevent cervical intraepithelial neoplasia (CIN). At the same time, the combined expression rate of P16 and OLFM4 increases with the aggravation of the degree of cervical lesions, which is combined to detect the shunt management of cervical cancer screening, early diagnosis and treatment of the disease, especially to divert CINII better. It is very important to provide an individualized diagnosis and treatment scheme.
【學(xué)位授予單位】：河北北方學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R737.33
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