SPAG9在宫颈腺癌中的表达及其临床意义

发布时间：2018-09-07 11:39

【摘要】：背景宫颈癌是最为常见的妇科恶性肿瘤之一,极大的威胁着广大女性的身体健康。近50年来,由于社会生活改变和人乳头状瘤病毒(HPV)感染人数增多,宫颈腺癌的发病有增加的趋势,且患者年轻化现象明显。宫颈腺癌、鳞癌这两种不同的病理类型在病因和发病机制上存在差别。宫颈原发腺癌由于病灶起源于宫颈管内,早期病灶隐匿,为宫颈局部的硬结,宫颈外观可无明显异常,多无症状,妇科检查常不被发现。宫颈癌的目前筛检方法主要为宫颈薄层液基细胞学。但由于宫颈腺癌病灶隐匿,因此细胞学检查阴性率高,容易造成漏诊。原发于宫颈的腺癌易与原发于子宫内膜的腺癌混淆,尤其是宫颈和子宫内膜均有病灶时,两者的诊治方法有很大的差别。宫颈腺癌的手术治疗创伤大、放化疗治疗副反应高,且与宫颈鳞癌相比预后差,因此宫颈腺癌的早期诊治、鉴别诊断和预后评估具有重要意义。目前,尚缺乏一种有效的分子生物学标记物可以有效协助宫颈腺癌的早期诊断、鉴别诊断、预后评估和靶向治疗。宫颈腺癌发病率低,关于它的研究少,因此探究一种新的有效的可以协助宫颈腺癌的早期诊断、鉴别诊断、预后评估的分子生物学标记物成为研究热点,也有助于探究宫颈腺癌的发病机制,并能够提供科学依据利于宫颈腺癌的分子靶向治疗的发展。目的研究宫颈腺癌组织中精子相关抗原-9(SPAG9)的表达及SPAG9在宫颈腺癌早期诊断、鉴别诊断、预后评估等方面的潜在临床应用价值,为宫颈腺癌的分子靶向治疗提供科学依据。方法研究对象自2007年1月起至2013年5月,在山东省立医院妇科就诊的50例宫颈腺癌患者和与之同期的年龄相匹配的50例宫颈无任何病变的的因子宫平滑肌瘤、子宫腺肌病等良性疾病行子宫全切术的患者。实验方法应用免疫组化SABC法,检测50例宫颈腺癌和50例正常宫颈组织中SPAG9蛋白的表达。结果1.临床资料分析该项研究中肿瘤组病例的平均初产年龄与正常宫颈组患者的平均初产年龄无显著性差异,肿瘤组初产年龄小于21岁的患者数目小于正常宫颈组,但两者差别没有统计学意义(P0.05)。肿瘤组孕次≥4次的患者数目大于正常宫颈组,但两者差别没有统计学意义(P0.05)。在这50例宫颈腺癌患者的调查中,宫颈腺癌的发病与孕次、初产年龄无关,不能支持宫颈腺癌的发病危险因素与多产等相关的观点。 2.染色结果本研究通过免疫组化的方法检测至SPAG9在正常宫颈组织中不表达(0%,0/18),在宫颈腺癌组织中高表达(100%,50/50), SPAG9蛋白主要表达于宫颈腺癌癌细胞的胞浆内,腺体周围的间质组织则很少表达,并且随着临床分期、病理分级,淋巴结转移的增加SPAG9蛋白表达逐渐增高,且在肿瘤病理分级中这种趋势有统计学意义(P0.05)。说明SPAG9在宫颈腺癌中的表达与肿瘤病理分级有相关性,与肿瘤分期和淋巴结转移无关。表明SPAG9存在于宫颈腺癌中,可能在宫颈腺癌的发生发展中发挥重要的作用。 3.不同预后的宫颈腺癌患者SPAG9染色H-score分析无论是所有的随访病例,随访满一年的病例、随访满两年病例、随访满三年病例还是随访满四年的病例,死亡病例的H-score分值均大于存活病例的H-score的分值。这既说明了在死亡病例中SPAG9蛋白的表达大于存活病例中SPAG9的表达,SPAG9可能促进了疾病的发生、进展,增加了疾病的恶性潜能,也说明了SPAG9表达水平的检测对于宫颈腺癌患者的预后预测具有重要意义。 4.不同病理类型对应的SPAG9染色结果由染色结果可以看出不同病理类型SPAG9表达量存在差异,但由于本次研究病例数目少,无法比较不同病理类型间SPAG9表达的差异性是否具有统计学意义。将SPAG9作为辅助诊断宫颈腺癌病理类型的标记分子仍有待进一步研究。 5.口服避孕药对SPAG9表达的影响讨论发病前长期吃避孕药的患者SPAG9H-score评分高于未应用避孕药避孕的患者,但差别无统计学意义(P0.05)。结论通过此次研究,我们发现SPAG9在宫颈腺癌中表达,在正常宫颈组织中不表达,且SPAG9的表达与肿瘤病理分级有相关性,与肿瘤分期和淋巴结转移无关。死亡病例中SPAG9H-score的分值均大于存活病例的H-score的分值。本次研究结果提示宫颈腺癌组与正常宫颈组在初产年龄、孕次无明显差异,不能支持多产等是宫颈腺癌发病危险因子的观点。由于病例数目少,口服避孕药患者数量很少,避孕药与SPAG9表达间的关系仍有待进一步研究考证。相同的原因,SPAG9作为辅助诊断宫颈腺癌病理类型的标记分子仍有待进一步研究。通过本次研究,我们可以看出SPAG9可能与宫颈腺癌的发生和发展有关,它在宫颈腺癌患者预后判断方面具有重要意义,具有成为作为宫颈腺癌早期诊断和预后评估和靶向治疗的生物学标记物的可能。
[Abstract]:Background Cervical cancer is one of the most common gynecological malignancies, which is a great threat to the health of women. In the past 50 years, the incidence of cervical adenocarcinoma has been increasing due to the change of social life and the increase of the number of HPV infection, and the phenomenon of younger patients is obvious. Cervical adenocarcinoma and squamous cell carcinoma are two different diseases. Cervical primary adenocarcinoma originates in the cervical canal and is occult in the early stage. It is a local induration of the cervix. The appearance of the cervix is not obvious abnormality and most of the symptoms are asymptomatic. Gynecological examination is often not found. Current screening methods for cervical cancer are mainly thin-layer liquid-based cytology of the cervix. Adenocarcinoma of the cervix is easily confused with adenocarcinoma of the endometrium, especially when both the cervix and the endometrium have lesions. The surgical treatment of cervical adenocarcinoma is traumatic, the side effects of radiotherapy and chemotherapy are high, and it is also different from that of the uterus. Cervical squamous cell carcinoma has a poor prognosis, so early diagnosis, differential diagnosis and prognostic evaluation of cervical adenocarcinoma are of great significance. At present, there is still a lack of an effective molecular biomarker that can effectively assist the early diagnosis, differential diagnosis, prognostic evaluation and targeted treatment of cervical adenocarcinoma. To explore a new and effective molecular biomarker for early diagnosis, differential diagnosis and prognosis evaluation of cervical adenocarcinoma has become a hot research topic. It can also help to explore the pathogenesis of cervical adenocarcinoma and provide scientific basis for the development of molecular targeted therapy of cervical adenocarcinoma.
Objective To study the expression of sperm-associated antigen-9 (SPAG9) in cervical adenocarcinoma and its potential clinical value in early diagnosis, differential diagnosis and prognosis evaluation of cervical adenocarcinoma.
Methods From January 2007 to May 2013, 50 patients with cervical adenocarcinoma and 50 patients with benign diseases such as uterine leiomyoma and adenomyosis without any cervical lesions were examined by immunohistochemical SABC. The expression of SPAG9 protein was detected in 50 cases of cervical adenocarcinoma and 50 cases of normal cervical tissue.
Results 1. There was no significant difference in the average age of primipara between the cancer group and the normal cervical group. The number of patients whose age of primipara was less than 21 years old in the cancer group was smaller than that in the normal cervical group, but there was no significant difference between the two groups (P 0.05). The number of patients with more than 4 pregnancies in the cancer group was larger than that in the normal cervical group. In the 50 cases of cervical adenocarcinoma, the incidence of cervical adenocarcinoma was not related to pregnancy and the age of first birth, and could not support the view that the risk factors of cervical adenocarcinoma were related to prolificacy.
2. The staining results showed that SPAG9 was not expressed in normal cervical tissues (0%, 0/18), was highly expressed in cervical adenocarcinoma tissues (100%, 50/50), SPAG9 was mainly expressed in the cytoplasm of cervical adenocarcinoma cells, but seldom expressed in the interstitial tissues around the gland, and with the clinical stage, pathological grade, gonorrhea. The expression of SPAG9 protein in cervical adenocarcinoma was correlated with the pathological grade of cervical adenocarcinoma, but not with the tumor stage and lymph node metastasis. The exhibition plays an important role.
3. SPAG9 staining H-score analysis of cervical adenocarcinoma patients with different prognosis showed that H-score of death cases was higher than H-score of survival cases in all follow-up cases, follow-up cases for more than one year, follow-up cases for more than two years, follow-up cases for more than three years or follow-up cases for more than four years. The expression of SPAG9 in white cells was higher than that in survivors. SPAG9 may promote the occurrence and progression of the disease and increase the malignant potential of the disease.
4. Different pathological types of SPAG9 staining results can be seen from the staining results of different pathological types of SPAG9 expression differences, but because the number of cases in this study is small, it is impossible to compare the different pathological types of SPAG9 expression is statistically significant. Molecular remains to be further studied.
5. The effect of oral contraceptives on the expression of SPAG9.
Conclusion Through this study, we found that SPAG9 was expressed in cervical adenocarcinoma, but not in normal cervical tissues, and the expression of SPAG9 was correlated with the pathological grade of cervical cancer, not with tumor stage and lymph node metastasis. The relationship between the expression of SPAG9 and the number of oral contraceptives remains to be further studied because of the small number of cases and the small number of oral contraceptives. Through this study, we can see that SPAG9 may be related to the occurrence and development of cervical adenocarcinoma. It is of great significance in the prognosis of patients with cervical adenocarcinoma and can be used as a biomarker for early diagnosis and prognosis evaluation and targeted therapy of cervical adenocarcinoma. It's possible.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.33

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