肾细胞癌中HOTAIR、EZH2表达情况及相关性研究
发布时间：2018-07-13 16:56
【摘要】：目的：根据最近几年的流行病学统计，肾细胞癌（RCC）的发病率有较为明显的上升势头，因此对于其发生、发展机制等得研究逐渐得到科学界的重视。肾癌是发生于肾脏实质的一种恶性肿瘤，具有多种病理类型，而其中90%为透明细胞癌。根据推测，其发病率与吸烟、饮酒以及高血压病等因素有关，但是具体机制等仍不明确。 长链非编码RNA从被发现起，就被认为是转录过程所产生的垃圾基因，但是随着生物科学技术的进步，以及研究的进步，科学家们已经确定其具有多种生物学功能，目前普遍认为，LncRNA主要的作用应该是在表观遗传学层面，但是整体的研究进展仍旧比较落后。由于科学家已经逐渐认同其巨大的生物学作用，因此更加关注对于长链非编码RNA的研究。而HOTAIR（HOX转录反义RNA）已经被证实在多种肿瘤中呈高表达，被认为是有价值的肿瘤分子标记物，并且有研究证实了HOTAIR在乳腺癌中作为骨架分子调控EZH2及其它相关分子甲基化与去甲基化的机制。本文主要通过检测HOTAIR基因mRNA及EZH2基因mRNA在肾细胞癌组织中的表达情况，并尝试论证其机制方面是否具有相关性。 方法： 1应用RT-PCR技术分别检测58例肾细胞癌组织和正常组织组织（均经过病例结果证实）中HOTAIR基因和EZH2基因mRNA的表达情况。 2运用统计软件SPSS17.0软件对数据进行统计学分析。 结果： 1肾细胞癌组织中HOTAIR基因mRNA的表达情况 HOTAIR基因在肾细胞癌和正常组织中的相对表达量分别为0.75±0.19和0.38±0.09，肾细胞癌组织中HOTAIR基因mRNA表达水平相对于正常组织表达水平显著高，两者的差异有统计学意义（P＜0.05）。 2肾细胞癌组织中EZH2基因mRNA的表达情况 EZH2基因在肾细胞癌和正常组织中的相对表达量分别为2.03±0.46和0.64±0.15肾细胞癌组织中EZH2基因mRNA表达量相对于正常组织显著高，两者的差异有统计学意义（P＜0.05）。 3肾细胞癌组织中HOTAIR基因和EZH2基因mRNA的表达情况与性别、年龄、是否有吸烟史、是否高血压病患者等个人情况以及临床分期、是否有淋巴结转移等临床病例资料的关系 按个人年龄进行分组并进行统计，年龄大于等于60岁组肿瘤组织中HOTAIR基因mRNA的相对表达量为0.75±0.22，年龄小于60岁组肿瘤组织中HOTAIR基因的mRNA基因的相对表达量为0.75±0.14，两者差异无统计学意义（P＞0.05）；年龄大于等于60岁组肿瘤组织中EZH2基因mRNA的相对表达量为2.10±0.49，年龄小于60岁组肿瘤组织中EZH2基因的mRNA基因的相对表达量为1.71±0.71，两者差异无统计学意义（P＞0.05）。 按性别进行分组并统计，男性患者组的肿瘤组织中HOTAIR基mRNA的相对表达量为0.73±0.20，女性患者组肿瘤组织中HOTAIR基因mRNA相对表达量为0.78±0.17，两者差异无统计学意义（P＞0.05）；男性患者组的肿瘤组织中EZH2基因mRNA的相对表达量为1.98±0.48，女性患者组肿瘤组织中EZH2基因mRNA相对表达量为2.18±0.40，两者差异无统计学意义（P＞0.05）。 按患者是否有吸烟史进行分组并统计，有吸烟史组患者肿瘤组织HOTAIR基因mRNA的相对表达量为0.75±0.16，无吸烟史组患者肿瘤组织中HOTAIR基因的mRNA的相对表达量为0.74±0.23，两者差异无统计学意义（P＞0.05）；有吸烟史组患者肿瘤组织中EZH2基因mRNA的相对表达量为1.98±0.47，无吸烟史组患者肿瘤组织中EZH2基因mRNA的相对表达量为2.20±0.42，两者差异无统计学意义（P＞0.05）。 按患者是否患者高血压病进行分组，高血压病患者组肿瘤组织中HOTAIR基因mRNA的相对表达量为0.72±0.19，无高血压病患者组肿瘤组织中HOTAIR基因的mRNA的相对表达量为0.81±0.18，两者差异无统计学意义（P＞0.05）；高血压病患者组肿瘤组织中EZH2基因mRNA的相对表达量为2.07±0.43，无高血压病患者组肿瘤组织中EZH2基因的mRNA的相对表达量为1.74±0.76，两者差异无统计学意义（P＞0.05）。 按肾细胞癌TNM分期进行分组，Ⅰ期肾细胞癌患者肿瘤组织中HOTAIR基因mRNA相对表达量为0.58±0.07，Ⅱ期肾细胞癌患者肿瘤组织中HOTAIR基因mRNA相对表达量为0.76±0.12，Ⅲ期肾细胞癌患者肿瘤组织中HOTAIR基因mRNA相对表达量为0.91±0.15，差异有统计学意义，Ⅲ期肾细胞癌患者肿瘤组织中HOTAIR基因mRNA相对表达量高于Ⅱ期肾细胞癌患者肿瘤组织中HOTAIR基因mRNA相对表达量，Ⅱ期肾细胞癌患者肿瘤组织中HOTAIR基因mRNA相对表达量高于Ⅰ期肾细胞癌患者肿瘤组织中HOTAIR基因mRNA相对表达量（P0.05）；Ⅰ期肾细胞癌患者肿瘤组织中EZH2基因mRNA相对表达量为1.68±0.37，，Ⅱ期肾细胞癌患者肿瘤组织中EZH2基因mRNA相对表达量为2.03±0.27，Ⅲ期肾细胞癌患者肿瘤组织中EZH2基因mRNA相对表达量为2.48±0.39，差异有统计学意义，Ⅲ期肾细胞癌患者肿瘤组织中EZH2基因mRNA相对表达量高于Ⅱ期肾细胞癌患者肿瘤组织中EZH2基因mRNA相对表达量，Ⅱ期肾细胞癌患者肿瘤组织中EZH2基因mRNA相对表达量高于Ⅰ期肾细胞癌患者肿瘤组织中EZH2基因mRNA相对表达量（P0.05）。 按是否有淋巴结转移分组，有淋巴结转移组的HOTAIR基因mRNA相对表达量为0.93±0.15，无淋巴结转移组的HOTAIR基因mRNA相对表达量为0.65±0.13，两者的差异有统计学意义（P＜0.05）；有淋巴结转移组的EZH2基因mRNA相对表达量为2.40±0.44，无淋巴结转移组EZH2基因的相对表达量为1.84±0.34，两者的差异有统计学意义（P＜0.05）。4肾细胞癌中HOTAIR基因mRNA相对表达量与EZH2基因mRNA相对表达量的相关性分析 肾细胞癌中HOTAIR基因mRNA相对表达量为0.75±0.19，EZH2基因mRNA相对表达量为2.03±0.46，两者呈明显的正相关关系（P＜0.05）。 结论： 1EZH2基因mRNA和HOTAIR基因mRNA在肾细胞癌中表达水平显著高于癌旁组织，两者均可能与肾细胞癌的发生、发展有关。 2EZH2和HOTAIR基因mRNA在肾细胞癌中的表达水平与患者年龄、性别、是否吸烟史、是否高血压病患者等因素无关，而与肿瘤临床分期、是否淋巴结转移相关，说明两者均可能与肿瘤的侵袭力以及预后有关。 3EZH2基因在肾细胞癌中mRNA表达水平与HOTAIR基因mRNA表达水平呈正相关，提示两者在肿瘤发生、发展的生物学机制上可能具有重要的联系。联合检测EZH2和HOTAIR，可能对于判断肿瘤恶性程度、侵袭力以及预后有一定参考价值。
[Abstract]:Objective: according to the epidemiological statistics of recent years, the incidence of renal cell carcinoma (RCC) has a more obvious upward trend. Therefore, the research on the pathogenesis of renal cell carcinoma has gradually gained the attention of the scientific community. The renal cancer is a malignant tumor occurring in the renal parenchyma, with a variety of pathological types, and 90% of them are clear cell carcinoma. It is presumed that its incidence is related to smoking, drinking and hypertension, but the specific mechanism is still not clear.
Long chain non coding RNA has been found to be a garbage gene produced by the process of transcription. However, with the progress of biological science and technology and the progress of research, scientists have identified a variety of biological functions. It is generally believed that the main role of LncRNA should be at the epigenetic level, but the overall study. Progress is still relatively backward. Since scientists have gradually recognized their enormous biological effects, they have paid more attention to the study of long chain non coded RNA. HOTAIR (HOX transcriptional antisense RNA) has been proved to be highly expressed in a variety of tumors and is considered a valuable tumor marker, and studies have confirmed that HOTAIR is in the mammary gland. The mechanisms of methylation and demethylation of EZH2 and other related molecules are regulated as a skeleton molecule in cancer. This article is mainly by detecting the expression of the HOTAIR gene mRNA and the EZH2 gene mRNA in the renal cell carcinoma tissue, and trying to demonstrate whether the mechanism is related.
Method:
1 the expression of HOTAIR gene and EZH2 gene mRNA were detected by RT-PCR technique in 58 cases of renal cell carcinoma and normal tissue (all confirmed by case results).
2 statistical analysis was performed using statistical software SPSS17.0.
Result:
MRNA expression of HOTAIR gene in 1 renal cell carcinoma
The relative expression of HOTAIR gene in renal cell carcinoma and normal tissue was 0.75 + 0.19 and 0.38 + 0.09 respectively. The expression level of HOTAIR gene mRNA in renal cell carcinoma tissues was significantly higher than that of normal tissue, and the difference between the two genes was statistically significant (P < 0.05).
MRNA expression of EZH2 gene in 2 renal cell carcinoma
The relative expression of EZH2 gene in renal cell carcinoma and normal tissue was 2.03 + 0.46 and 0.64 + 0.15 in renal cell carcinoma tissues. The mRNA expression of EZH2 gene was significantly higher than that of normal tissue. The difference was statistically significant (P < 0.05).
The relationship between the expression of HOTAIR and EZH2 gene mRNA in 3 renal cell carcinoma and the relationship between sex, age, smoking history, individual situation of hypertensive patients, clinical staging, lymph node metastasis and other clinical cases
The relative expression of HOTAIR gene mRNA in the tumor tissues of the 60 year old group was 0.75 + 0.22, and the relative expression of the mRNA gene of HOTAIR gene in the tumor tissues under the age of 60 years old was 0.75 + 0.14, and the difference was not statistically significant (P > 0.05), and the age was greater than that of the 60 year old tumor. The relative expression of the EZH2 gene mRNA in the tissue was 2.10 + 0.49, and the relative expression of the mRNA gene of the EZH2 gene in the tumor tissue aged less than 60 years was 1.71 + 0.71, and the difference was not statistically significant (P > 0.05).
The relative expression of HOTAIR based mRNA in the tumor tissues of the male patients was 0.73 + 0.20, and the relative expression of the HOTAIR gene mRNA in the tumor tissues of the female patients was 0.78 + 0.17, and the difference was not statistically significant (P > 0.05). The relative expression of the EZH2 gene mRNA in the tumor tissues of the male patients was 1.98. (0.48) the relative expression of EZH2 gene mRNA in tumor tissues of female patients was 2.18 + 0.40, and there was no significant difference between them (P > 0.05).
According to whether the patient had a history of smoking, the relative expression of the HOTAIR gene mRNA in the tumor tissue was 0.75 + 0.16, and the relative expression of mRNA in the tumor tissue of the non smoking group was 0.74 + 0.23, and the difference was not statistically significant (P > 0.05), and there was EZH in the tumor tissue of the smoking history group. The relative expression of the 2 gene mRNA was 1.98 + 0.47, and the relative expression of the EZH2 gene mRNA in the non smoking history group was 2.20 + 0.42, and the difference was not statistically significant (P > 0.05).
According to the group of patients with hypertension, the relative expression of HOTAIR gene mRNA in the tumor tissue of the patients with hypertension was 0.72 + 0.19. The relative expression of the mRNA of HOTAIR gene in the tumor tissue of the non hypertensive group was 0.81 + 0.18, and the difference was not statistically significant (P > 0.05). The relative expression of the EZH2 gene mRNA was 2.07 + 0.43. The relative expression of mRNA in the tumor tissues of the non hypertensive patients was 1.74 + 0.76, and the difference between the two genes was not statistically significant (P > 0.05).
According to the TNM stage of renal cell carcinoma, the relative expression of HOTAIR gene mRNA in the tumor tissues of stage I renal cell carcinoma was 0.58 + 0.07. The relative expression of HOTAIR gene mRNA in the tumor tissues of stage II renal cell carcinoma patients was 0.76 + 0.12, and the relative expression of HOTAIR gene mRNA in the tumor tissues of stage III renal cell carcinoma patients was 0.91 + 0.15, and the difference was found. The relative expression of HOTAIR gene mRNA in tumor tissues of stage III renal cell carcinoma patients is higher than that of HOTAIR gene mRNA in the tumor tissues of stage II renal cell carcinoma patients. The relative expression of HOTAIR gene mRNA in tumor tissues of stage II renal cell carcinoma patients is higher than that of HOTAIR gene mRNA in the tumor tissues of stage I renal cell carcinoma patients. The relative expression of EZH2 gene mRNA in tumor tissues of patients with stage I renal cell carcinoma was 1.68 + 0.37. The relative expression of EZH2 gene mRNA in tumor tissues of stage II renal cell carcinoma patients was 2.03 + 0.27. The relative expression of EZH2 gene mRNA in tumor tissues of stage III renal cell carcinoma patients was 2.48 + 0.39, and the difference was statistically significant. The relative expression of EZH2 gene mRNA in tumor tissues of renal cell carcinoma patients is higher than that of EZH2 gene mRNA in the tumor tissues of stage II renal cell carcinoma patients. The relative expression of EZH2 gene mRNA in tumor tissues of stage II renal cell carcinoma patients is higher than the relative expression of EZH2 gene mRNA in tumor tissues of stage I renal cell carcinoma patients (P0.05).
According to the lymph node metastasis group, the relative expression of HOTAIR gene mRNA in the lymph node metastasis group was 0.93 + 0.15, and the relative expression of HOTAIR gene mRNA in the non lymph node metastasis group was 0.65 + 0.13, and the difference between the two groups was statistically significant (P < 0.05). The EZH2 gene mRNA relative expression of the lymph node metastasis group was 2.40 + 0.44, and no lymph node was found. The relative expression of EZH2 gene in the transfer group was 1.84 + 0.34, and the difference was statistically significant (P < 0.05) the correlation analysis of the relative expression of HOTAIR gene mRNA and the relative expression of EZH2 gene mRNA in.4 renal cell carcinoma
The relative expression of HOTAIR gene mRNA in renal cell carcinoma was 0.75 + 0.19, and the relative expression of EZH2 gene mRNA was 2.03 + 0.46, showing a significant positive correlation (P < 0.05).
Conclusion:
The expression level of 1EZH2 gene mRNA and HOTAIR mRNA in renal cell carcinoma is significantly higher than that in adjacent tissues, both of which may be related to the occurrence and development of renal cell carcinoma.
The expression level of 2EZH2 and HOTAIR gene mRNA in renal cell carcinoma is not related to the patient's age, sex, smoking history and hypertension, but it is related to the tumor clinical stage and lymph node metastasis, indicating that both of them may be related to the invasion and prognosis of the tumor.
The level of mRNA expression of 3EZH2 gene in renal cell carcinoma is positively correlated with the level of mRNA expression of HOTAIR gene, suggesting that both of them may have important relationship with the biological mechanism of tumor development and development. The combined detection of EZH2 and HOTAIR may be of reference value for judging the malignancy, invasion force and prognosis of tumor.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.11
本文编号：2120098
[Abstract]:Objective: according to the epidemiological statistics of recent years, the incidence of renal cell carcinoma (RCC) has a more obvious upward trend. Therefore, the research on the pathogenesis of renal cell carcinoma has gradually gained the attention of the scientific community. The renal cancer is a malignant tumor occurring in the renal parenchyma, with a variety of pathological types, and 90% of them are clear cell carcinoma. It is presumed that its incidence is related to smoking, drinking and hypertension, but the specific mechanism is still not clear.
Long chain non coding RNA has been found to be a garbage gene produced by the process of transcription. However, with the progress of biological science and technology and the progress of research, scientists have identified a variety of biological functions. It is generally believed that the main role of LncRNA should be at the epigenetic level, but the overall study. Progress is still relatively backward. Since scientists have gradually recognized their enormous biological effects, they have paid more attention to the study of long chain non coded RNA. HOTAIR (HOX transcriptional antisense RNA) has been proved to be highly expressed in a variety of tumors and is considered a valuable tumor marker, and studies have confirmed that HOTAIR is in the mammary gland. The mechanisms of methylation and demethylation of EZH2 and other related molecules are regulated as a skeleton molecule in cancer. This article is mainly by detecting the expression of the HOTAIR gene mRNA and the EZH2 gene mRNA in the renal cell carcinoma tissue, and trying to demonstrate whether the mechanism is related.
Method:
1 the expression of HOTAIR gene and EZH2 gene mRNA were detected by RT-PCR technique in 58 cases of renal cell carcinoma and normal tissue (all confirmed by case results).
2 statistical analysis was performed using statistical software SPSS17.0.
Result:
MRNA expression of HOTAIR gene in 1 renal cell carcinoma
The relative expression of HOTAIR gene in renal cell carcinoma and normal tissue was 0.75 + 0.19 and 0.38 + 0.09 respectively. The expression level of HOTAIR gene mRNA in renal cell carcinoma tissues was significantly higher than that of normal tissue, and the difference between the two genes was statistically significant (P < 0.05).
MRNA expression of EZH2 gene in 2 renal cell carcinoma
The relative expression of EZH2 gene in renal cell carcinoma and normal tissue was 2.03 + 0.46 and 0.64 + 0.15 in renal cell carcinoma tissues. The mRNA expression of EZH2 gene was significantly higher than that of normal tissue. The difference was statistically significant (P < 0.05).
The relationship between the expression of HOTAIR and EZH2 gene mRNA in 3 renal cell carcinoma and the relationship between sex, age, smoking history, individual situation of hypertensive patients, clinical staging, lymph node metastasis and other clinical cases
The relative expression of HOTAIR gene mRNA in the tumor tissues of the 60 year old group was 0.75 + 0.22, and the relative expression of the mRNA gene of HOTAIR gene in the tumor tissues under the age of 60 years old was 0.75 + 0.14, and the difference was not statistically significant (P > 0.05), and the age was greater than that of the 60 year old tumor. The relative expression of the EZH2 gene mRNA in the tissue was 2.10 + 0.49, and the relative expression of the mRNA gene of the EZH2 gene in the tumor tissue aged less than 60 years was 1.71 + 0.71, and the difference was not statistically significant (P > 0.05).
The relative expression of HOTAIR based mRNA in the tumor tissues of the male patients was 0.73 + 0.20, and the relative expression of the HOTAIR gene mRNA in the tumor tissues of the female patients was 0.78 + 0.17, and the difference was not statistically significant (P > 0.05). The relative expression of the EZH2 gene mRNA in the tumor tissues of the male patients was 1.98. (0.48) the relative expression of EZH2 gene mRNA in tumor tissues of female patients was 2.18 + 0.40, and there was no significant difference between them (P > 0.05).
According to whether the patient had a history of smoking, the relative expression of the HOTAIR gene mRNA in the tumor tissue was 0.75 + 0.16, and the relative expression of mRNA in the tumor tissue of the non smoking group was 0.74 + 0.23, and the difference was not statistically significant (P > 0.05), and there was EZH in the tumor tissue of the smoking history group. The relative expression of the 2 gene mRNA was 1.98 + 0.47, and the relative expression of the EZH2 gene mRNA in the non smoking history group was 2.20 + 0.42, and the difference was not statistically significant (P > 0.05).
According to the group of patients with hypertension, the relative expression of HOTAIR gene mRNA in the tumor tissue of the patients with hypertension was 0.72 + 0.19. The relative expression of the mRNA of HOTAIR gene in the tumor tissue of the non hypertensive group was 0.81 + 0.18, and the difference was not statistically significant (P > 0.05). The relative expression of the EZH2 gene mRNA was 2.07 + 0.43. The relative expression of mRNA in the tumor tissues of the non hypertensive patients was 1.74 + 0.76, and the difference between the two genes was not statistically significant (P > 0.05).
According to the TNM stage of renal cell carcinoma, the relative expression of HOTAIR gene mRNA in the tumor tissues of stage I renal cell carcinoma was 0.58 + 0.07. The relative expression of HOTAIR gene mRNA in the tumor tissues of stage II renal cell carcinoma patients was 0.76 + 0.12, and the relative expression of HOTAIR gene mRNA in the tumor tissues of stage III renal cell carcinoma patients was 0.91 + 0.15, and the difference was found. The relative expression of HOTAIR gene mRNA in tumor tissues of stage III renal cell carcinoma patients is higher than that of HOTAIR gene mRNA in the tumor tissues of stage II renal cell carcinoma patients. The relative expression of HOTAIR gene mRNA in tumor tissues of stage II renal cell carcinoma patients is higher than that of HOTAIR gene mRNA in the tumor tissues of stage I renal cell carcinoma patients. The relative expression of EZH2 gene mRNA in tumor tissues of patients with stage I renal cell carcinoma was 1.68 + 0.37. The relative expression of EZH2 gene mRNA in tumor tissues of stage II renal cell carcinoma patients was 2.03 + 0.27. The relative expression of EZH2 gene mRNA in tumor tissues of stage III renal cell carcinoma patients was 2.48 + 0.39, and the difference was statistically significant. The relative expression of EZH2 gene mRNA in tumor tissues of renal cell carcinoma patients is higher than that of EZH2 gene mRNA in the tumor tissues of stage II renal cell carcinoma patients. The relative expression of EZH2 gene mRNA in tumor tissues of stage II renal cell carcinoma patients is higher than the relative expression of EZH2 gene mRNA in tumor tissues of stage I renal cell carcinoma patients (P0.05).
According to the lymph node metastasis group, the relative expression of HOTAIR gene mRNA in the lymph node metastasis group was 0.93 + 0.15, and the relative expression of HOTAIR gene mRNA in the non lymph node metastasis group was 0.65 + 0.13, and the difference between the two groups was statistically significant (P < 0.05). The EZH2 gene mRNA relative expression of the lymph node metastasis group was 2.40 + 0.44, and no lymph node was found. The relative expression of EZH2 gene in the transfer group was 1.84 + 0.34, and the difference was statistically significant (P < 0.05) the correlation analysis of the relative expression of HOTAIR gene mRNA and the relative expression of EZH2 gene mRNA in.4 renal cell carcinoma
The relative expression of HOTAIR gene mRNA in renal cell carcinoma was 0.75 + 0.19, and the relative expression of EZH2 gene mRNA was 2.03 + 0.46, showing a significant positive correlation (P < 0.05).
Conclusion:
The expression level of 1EZH2 gene mRNA and HOTAIR mRNA in renal cell carcinoma is significantly higher than that in adjacent tissues, both of which may be related to the occurrence and development of renal cell carcinoma.
The expression level of 2EZH2 and HOTAIR gene mRNA in renal cell carcinoma is not related to the patient's age, sex, smoking history and hypertension, but it is related to the tumor clinical stage and lymph node metastasis, indicating that both of them may be related to the invasion and prognosis of the tumor.
The level of mRNA expression of 3EZH2 gene in renal cell carcinoma is positively correlated with the level of mRNA expression of HOTAIR gene, suggesting that both of them may have important relationship with the biological mechanism of tumor development and development. The combined detection of EZH2 and HOTAIR may be of reference value for judging the malignancy, invasion force and prognosis of tumor.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.11
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相关期刊论文 前2条
1 杨韬;李俊堂;王丽娟;李伟;郭张燕;白文栋;杨安钢;;干涉lncRNAs HOTAIR对人乳腺癌细胞MDA-MB-231的影响[J];细胞与分子免疫学杂志;2012年01期
2 孙奋勇;;解码基因组中的“暗物质”[J];同济大学学报(医学版);2011年01期
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