PTEN与miR-215在视网膜母细胞瘤中的表达及临床意义

吴康平; 黄静; 王丽娜; 叶蓓; 朱亚楠

doi:10.16766/j.cnki.issn.1674-4152.003746

PTEN与miR-215在视网膜母细胞瘤中的表达及临床意义

doi: 10.16766/j.cnki.issn.1674-4152.003746

杭州市儿童医院儿呼吸内科，浙江杭州 310002

基金项目:

国家自然科学基金项目 81970779

详细信息

通讯作者:
王丽娜，E-mail：wang819lina819@163.com

中图分类号: R739.72
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- 文章访问数: 15
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- 被引次数: 0
出版历程
- 收稿日期: 2024-03-19
- 网络出版日期: 2024-12-31

The expression and clinical significance of PTEN and miR-215 in retinoblastoma

Department of Pediatric Respiratory, Hangzhou Children' s Hospital, Hangzhou, Zhejiang 310002, China

摘要

摘要: 目的视网膜母细胞瘤(RB)会影响患儿的视力和生命，本研究旨在通过研究第10号染色体同源缺失性磷酸酶-张力蛋白(PTEN)与miR-215在RB中的表达和临床意义，为患儿的个体化治疗和预后评估提供指导。方法选择杭州市儿童医院2020年8月—2023年10月诊治的80例RB患儿，分别取癌组织与癌旁正常组织，采用RT-PCR法检测组织中miR-215表达，免疫组化法检测PTEN表达，并采用Cox风险回归模型分析PTEN和miR-215表达与RB病理参数及预后的关系。结果 RB组织的PTEN阳性率(65.00%，52/80)显著低于癌旁组织(100.00%, 80/80)，miR-215表达水平显著低于癌旁组织(P＜0.05)；PTEN阴性表达组患儿总生存时间(OS)明显短于PTEN阳性表达组患儿，miR-215低表达组患儿OS明显短于miR-215高表达组患儿(P＜0.05)；Cox回归分析显示临床分期Ⅲ期(HR=3.047，95% CI：1.117~8.311，P=0.030)、未分化(HR=2.907，95% CI：1.452~5.817，P=0.003)、有视神经浸润(HR=4.446，95% CI：1.311~15.076，P=0.017)、miR-215低表达(HR=2.854，95% CI：1.211~6.604，P=0.018)和PTEN阴性表达(HR=3.823，95% CI：1.708~8.555，P=0.001)均为RB患儿预后不良的独立危险因素(P＜0.05)。结论 RB患儿存在PTEN阳性率降低、miR-215低表达现象，且PTEN阴性表达、miR-215低表达是导致RB预后不良的危险因素。
- 视网膜母细胞瘤 /
- 第10号染色体同源缺失性磷酸酶-张力蛋白 /
- miR-215 /
- 预后
Abstract: Objective Retinoblastoma (RB) can impair the vision and threaten the lives of children. The purpose of this study is to provide guidance for individualized treatment and prognosis assessment of children by investigating the expression and clinical significance of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and miR-215 in RB. Methods A total of 80 children with RB, diagnosed and treated in Hangzhou Children ' s Hospital from August 2020 to October 2023 were selected for the study. Cancerous tissues and adjacent normal tissues were collected, with miR-215 levels detected by RT-PCR and PTEN expression evaluated by immunohistochemical method, respectively. Cox risk regression model was used to analyze the relationship among the expression of PTEN, miR-215, pathological parameters and prognosis of RB. Results The positive rate of PTEN [65.00% (52/80) vs. 100.00% (80/80)] and the expression level of miR-215 in RB tissues were significantly lower than those in adjacent normal tissues (P < 0.05). The overall survival (OS) was significantly reduced in both the PTEN-negative expression group and the OS in miR-215 low-expression group (P < 0.05). Cox regression analysis showed that stage Ⅲ (HR=3.047, 95% CI: 1.117-8.311, P=0.030), undifferentiated tumors (HR=2.907, 95% CI: 1.452-5.817, P=0.003), optic nerve infiltration (HR=4.446, 95% CI: 1.311-15.076, P=0.017), low expression of miR-215 (HR=2.854, 95% CI: 1.211-6.604, P=0.018), and negative expression of PTEN (HR=3.823, 95% CI: 1.708-8.555, P=0.001) as independent risk factors for poor prognosis in RB children (P < 0.05). Conclusion The decrease of positive rate of PTEN and low expression of miR-215 are observed in RB children, and these factors are risk factors associated with poor prognosis of RB.
- Retinoblastoma /
- Phosphatase and tensin homolog deleted on chromosome ten /
- miR-215 /
- Prognosis

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图 1 不同PTEN表达水平RB患儿生存分析

Figure 1. Survival analysis of RB children with different PTEN expression levels

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图 2 不同miR-215表达水平RB患儿生存分析

Figure 2. Survival analysis of RB children with different miR-215 expression levels

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表 1 引物序列

Table 1. Primer sequences

目的基因及内参	上游序列	下游序列
β-actin	5’-CCTGTACGCCAACACAGTGC-3’	5’-ATACTCCTGCTTGCTGATCC-3’
miR-215	5’-TCCGATTCTTCACGTGGTAC-3’	5’-GTGCAGGGTCCGAGGT-3’

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表 2 癌组织和癌旁组织PTEN、miR-215表达水平比较

Table 2. Comparison of PTEN and miR-215 expression levels in cancer and adjacent tissues

组别	例数	PTEN					miR-215 (x±s)
组别	例数	阴性(例)	弱阳性(例)	阳性(例)	强阳性(例)	阳性率(%)	miR-215 (x±s)
癌旁组织	80	0	8	32	40	100.00	1.28±0.34
癌组织	80	28	14	21	17	65.00	1.04±0.21
统计量						33.939^a	7.806^b
P值						＜0.001	＜0.001
注：^a为χ²值，^b为t值。

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表 3 不同PTEN、miR-215表达水平RB患儿病理参数比较

Table 3. Comparison of pathological parameters in RB children with different PTEN and miR-215 expression levels

项目	例数	PTEN阳性 [例(%)]	χ²值	P值	miR-215 (x±s)	统计量	P值
年龄
≥3岁	21	11(52.38)	1.993	0.158	1.05±0.19	0.185^a	0.854
＜3岁	59	41(69.49)			1.04±0.22
性别
男	28	16(57.14)	1.169	0.280	1.09±0.24	1.431^a	0.156
女	52	36(69.23)			1.02±0.19
临床分期
Ⅰ期	26	22(84.62)	7.580	0.023	1.28±0.25	34.055^b	＜0.001
Ⅱ期	22	14(63.64)			1.06±0.20
Ⅲ期	32	16(50.00)			0.83±0.17
病理分型
分化型	39	31(79.49)	7.020	0.008	1.22±0.17	7.285^a	＜0.001
未分化型	41	21(51.22)			0.87±0.25
视神经浸润
有	52	28(53.85)	8.125	0.004	0.93±0.20	6.557^a	＜0.001
无	28	24(85.71)			1.26±0.24
发病侧
左侧	32	22(68.75)	0.330	0.566	1.08±0.20	1.397^a	0.166
右侧	48	30(62.50)			1.02±0.18
注：^a为t值，^b为F值。

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表 4 变量赋值情况

Table 4. Variable assignment

变量	赋值方法
年龄	≥3岁=1，＜3岁=2
性别	男=1，女=2
临床分期	Ⅰ期=1，Ⅱ期=2，Ⅲ期=3
病理分型	分化型=1，未分化型=2
视神经浸润	有=1，无=2
PTEN	阳性表达=1，阴性表达=2
miR-215	低表达=1，高表达=2
预后	预后良好=1，预后不良=2

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表 5 RB患儿预后影响因素的Cox回归分析

Table 5. Cox regression analysis of factors influencing prognosis in RB children

变量	单因素		多因素
变量	HR(95% CI)	P值	HR(95% CI)	P值
临床分期为Ⅲ期	2.812(1.151~6.874)	0.024	3.047(1.117~8.311)	0.030
未分化	2.601(2.089~3.240)	＜0.001	2.907(1.452~5.817)	0.003
有视神经浸润	4.768(1.748~13.007)	0.002	4.446(1.311~15.076)	0.017
PTEN阴性表达	3.651(1.857~7.179)	＜0.001	3.823(1.708~8.555)	0.001
miR-215低表达	4.735(1.699~13.198)	0.003	2.854(1.211~6.604)	0.018

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