非小细胞肺癌组织LncRNA MIR503HG、Wnt1表达与患者术后5年内生存的相关性

doi:10.11958/20230852

天津医药 ›› 2024, Vol. 52 ›› Issue (4): 403-408.doi: 10.11958/20230852

非小细胞肺癌组织LncRNA MIR503HG、Wnt1表达与患者术后5年内生存的相关性

秦爱英(), 陈静, 单风晓, 陆翰杰, 武阳^△()

郑州大学附属洛阳中心医院肿瘤三病区（邮编471000）

收稿日期:2023-06-16 修回日期:2023-10-08 出版日期:2024-04-15 发布日期:2024-04-19
通讯作者: ^△E-mail：761278201@qq.com
作者简介:秦爱英（1986），女，主治医师，主要从事恶性肿瘤的综合诊疗研究。E-mail：qinaiy827@163.com
基金资助:
河南省医学科技攻关计划（联合共建）项目(LHGJ20210173)

The correlation between expression of lncRNA MIR503HG and Wnt1 in non-small cell lung cancer tissue and patient survival within 5 years after surgery

QIN Aiying(), CHEN Jing, SHAN Fengxiao, LU Hanjie, WU Yang^△()

Three Disease Areas of Tumor, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471000, China

Received:2023-06-16 Revised:2023-10-08 Published:2024-04-15 Online:2024-04-19
Contact: ^△E-mail：761278201@qq.com

秦爱英, 陈静, 单风晓, 陆翰杰, 武阳. 非小细胞肺癌组织LncRNA MIR503HG、Wnt1表达与患者术后5年内生存的相关性[J]. 天津医药, 2024, 52(4): 403-408.

QIN Aiying, CHEN Jing, SHAN Fengxiao, LU Hanjie, WU Yang. The correlation between expression of lncRNA MIR503HG and Wnt1 in non-small cell lung cancer tissue and patient survival within 5 years after surgery[J]. Tianjin Medical Journal, 2024, 52(4): 403-408.

摘要/Abstract

摘要：

目的探究非小细胞肺癌（NSCLC）组织中长链非编码RNA（LncRNA）miR503宿主基因（MIR503HG）、Wnt1表达水平与患者术后5年内生存的关系。方法纳入108例NSCLC患者，并于术中收集患者肺癌组织和癌旁组织。荧光定量PCR法检测肺癌及癌旁组织中LncRNA MIR503HG、Wnt1 mRNA表达水平；免疫组织化学染色检测肺癌及癌旁组织中Wnt1蛋白表达。对NSCLC患者术后随访5年，记录随访期内生存状况。比较癌旁组织、肺癌组织中LncRNA MIR503HG、Wnt1 mRNA和蛋白阳性表达情况；比较不同结局NSCLC患者肺癌组织中两者表达水平及其在不同临床病理特征中的差异；Pearson法分析肺癌组织中两者表达水平的相关性；Kaplan-Meier生存曲线分析肺癌组织中两者表达水平与患者术后5年内生存的关系；多因素Cox回归分析NSCLC患者术后5年内生存的影响因素；受试者工作特征（ROC）曲线评估肺癌组织LncRNA MIR503HG、Wnt1 mRNA表达水平对患者术后5年内生存的预测价值。结果肺癌组织中LncRNA MIR503HG表达水平低于癌旁组织，Wnt1 mRNA表达水平和Wnt1蛋白阳性表达率高于癌旁组织（P<0.05）。低分化、TNM分期Ⅲ期、有淋巴结转移NSCLC患者肺癌组织LncRNA MIR503HG表达水平分别低于中高分化、TNM分期Ⅰ—Ⅱ期、无淋巴结转移NSCLC患者；Wnt1 mRNA表达水平分别高于中高分化、TNM分期Ⅰ—Ⅱ期、无淋巴结转移NSCLC患者（P<0.05）。肺癌组织中LncRNA MIR503HG与Wnt1 mRNA表达水平呈负相关（P<0.05）。108例NSCLC患者术后随访5年，生存48例（生存组），死亡60例（死亡组）；LncRNA MIR503HG高表达组、Wnt1 mRNA低表达组术后5年累积生存率分别高于LncRNA MIR503HG低表达组和Wnt1 mRNA高表达组（P<0.05）。与生存组相比，死亡组肺癌组织LncRNA MIR503HG表达水平降低，Wnt1 mRNA表达水平升高（P<0.05）。肺癌组织LncRNA MIR503HG低表达、Wnt1 mRNA高表达、低分化、TNM分期为Ⅲ期、有淋巴结转移均是影响NSCLC患者术后5年内生存的独立危险因素（P<0.05）。肺癌组织LncRNA MIR503HG、Wnt1 mRNA及二者联合预测NSCLC患者术后5年内生存的曲线下面积（AUC）分别为0.823、0.728和0.885，联合预测效能更高（P<0.05）。结论 NSCLC患者肺癌组织中LncRNA MIR503HG呈低表达，Wnt1呈高表达，二者与患者临床病理特征和术后5年内生存情况密切相关，对患者术后5年内生存情况有较高预测价值。

关键词: 癌, 非小细胞肺, RNA, 长链非编码, Wnt1蛋白质, miR503宿主基因

Abstract:

Objective To explore the relationship between expression levels of long non-coding RNA (lncRNA) miR503 host gene (MIR503HG) and Wnt1 in non small cell lung cancer (NSCLC) tissue and the survival of patients within 5 years after surgery. Methods A total of 108 NSCLC patients were selected for this study, and lung cancer tissue and paracancer tissue of patients were collected during operation. Fluorescence quantitative PCR was used to detect lncRNA MIR503HG and Wnt1 mRNA expression levels in lung cancer tissue and paracancer tissue. The expression levels of Wnt1 protein in lung cancer tissue and paracancer tissue were determined by immunohistochemistry. Patients with NSCLC were follow up for 5 years after surgery, and their survival status was recorded during the follow-up period. The positive expression of lncRNA MIR503HG and Wnt1 mRNA and protein in paracancer tissue and lung cancer tissue were compared. The expression levels of the above two in lung cancer tissue of NSCLC patients with different outcomes and their differences in different clinicopathological characteristics were compared. Pearson method was used to analyze the correlation between the two expression levels in lung cancer tissue. Kaplan-Meier survival curve was used to analyze the relationship between the expression levels of both in lung cancer tissue and the survival of patients within 5 years after operation. Multivariate Cox regression analysis was used to analyze factors affecting the survival in patients with NSCLC within 5 years after surgery. Receiver operating characteristics (ROC) curves were used to evaluate the predictive values of lncRNA MIR503HG and Wnt1 mRNA expression levels in lung cancer tissue in patients with 5-year postoperative survival. Results LncRNA MIR503HG expression level in lung cancer tissue was lower than those in paracancer tissue. Wnt1 mRNA expression level and Wnt1 protein positive expression rate were higher in lung cancer tissue than that in paracancer tissue (P<0.05). The expression level of lncRNA MIR503HG in lung cancer tissue of NSCLC patients with low differentiation, stage Ⅲ and lymph node metastasis was lower than that of NSCLC patients with medium-high differentiation, stage I-Ⅱ and no lymph node metastasis. The expression level of Wnt1 mRNA in lung cancer tissue of NSCLC patients with low differentiation, stage Ⅲ and lymph nodemetastasis was higher than that of NSCLC patients with medium-high differentiation, stage I-Ⅱ and no lymph node metastasis, respectively (P<0.05). LncRNA MIR503HG and the Wnt1 mRNA expression levels in lung cancer tissue were negatively correlated (P<0.05). A total of 108 NSCLC patients were followed up for 5 years after surgery, with 48 surviving patients (the survival group) and 60 deaths (the death group). The 5-year cumulative survival rate after surgery was higher in the lncRNA MIR503HG high expression group and the Wnt1 mRNA low expression group than that of the lncRNA MIR503HG low expression group and the Wnt1 mRNA high expression group, respectively (P<0.05). Compared with the survival group, lncRNA MIR503HG expression level of lung cancer tissue was decreased and Wnt1 mRNA expression level was increased in the death group (P<0.05). The low expression of lncRNA MIR503HG, high expression of Wnt1 mRNA, low differentiation, stage Ⅲ TNM and lymph node metastasis in lung cancer tissue were all independent risk factors affecting the survival of patients with NSCLC within 5 years after surgery (P<0.05). The area under curve (AUC) of lncRNA MIR503HG, Wnt1 mRNA and their combined in predicting 5-year survival after surgery in NSCLC patients were 0.823, 0.728 and 0.885, respectively, and the combined forecasting was more efficient (P<0.05). Conclusion Low expression of lncRNA MIR503HG and high expression of Wnt1 in lung cancer tissue of NSCLC patients are closely related to the clinicopathological features and survival of patients within 5 years after surgery, and which have a high predictive value for the survival of patients within 5 years after surgery.

Key words: carcinoma, nonsmall-cell lung, RNA, long noncoding, Wnt1 protein, miR503 host gene

中图分类号:

R734.2

图/表 10

表1 引物序列

Tab.1 Primer sequence

基因名称	引物序列（5′→3′）	产物大小/bp
LncRNA MIR503HG	上游：TGCTGTCGATGGTGCGTAGC 下游：ACTGAGAATGTACCAAGGAG	186
Wnt1	上游：TCCACGCAGCTTACCAGGCACGA	192
	下游：AATGAAGCAGAGGAGTCTGTTC	192
GAPDH	上游：GGTCCATTCATCGTGATAACA	238
	下游：ACCATCGGGCGTCGCTCCTGT	238

表2 肺癌及癌旁组织中LncRNA MIR503HG、Wnt1 mRNA表达水平比较（$\bar{x}±s$）

Tab.2 Comparison of lncRNA MIR503HG and Wnt1 mRNA expression levels between lung cancer tissue and paracancer tissue

组别	n	LncRNA MIR503HG	Wnt1 mRNA
癌旁组织	108	1.00±0.07	1.00±0.09
肺癌组织	108	0.58±0.12	1.88±0.46
t		31.418^＊＊	19.511^＊＊

图1 癌旁组织和肺癌组织中Wnt1蛋白表达（免疫组织化学染色） A、C为癌旁组织（×400）；B、D为肺癌组织（×100）。

Fig.1 Expression of Wnt1 protein in paracancer tissue and lung cancer tissue (immunohistochemical staining)

表3 不同临床病理特征患者肺癌组织中LncRNA MIR503HG、Wnt1 mRNA表达水平比较（$\bar{x}±s$）

Tab.3 Comparison of lncRNA MIR503HG and Wnt1 mRNA expression levels in lung cancer tissue between patients with different clinicopathological characteristics

临床病理特征	n	LncRNA MIR503HG	t	Wnt1 mRNA	t
性别
男	69	0.59±0.14	1.228	1.82±0.44	1.835
女	39	0.56±0.08	1.228	1.99±0.50	1.835
年龄
<55岁	71	0.59±0.12	1.233	1.84±0.47	1.277
≥55岁	37	0.56±0.12	1.233	1.96±0.45	1.277
病理类型
腺癌	68	0.57±0.11	0.852	1.86±0.45	0.658
鳞癌	40	0.59±0.13	0.852	1.92±0.47	0.658
肿瘤直径
<3 cm	76	0.57±0.12	1.186	1.86±0.44	0.735
≥3 cm	32	0.60±0.12	1.186	1.93±0.48	0.735
病理分级
中高分化	78	0.64±0.15	7.905^＊＊	1.75±0.41	4.693^＊＊
低分化	30	0.42±0.04	7.905^＊＊	2.22±0.59	4.693^＊＊
TNM分期
Ⅰ—Ⅱ期	80	0.65±0.14	9.869^＊＊	1.77±0.44	4.143^＊＊
Ⅲ期	28	0.38±0.06	9.869^＊＊	2.19±0.52	4.143^＊＊
淋巴结转移
无	47	0.63±0.14	3.326^＊＊	1.75±0.40	2.580^＊
有	61	0.55±0.11	3.326^＊＊	1.98±0.50	2.580^＊

图2 LncRNA MIR503HG不同表达水平NSCLC患者术后5年生存曲线图中检剔后即为删失。

Fig.2 Five-year survival curve of NSCLC patients with different expression levels of lncRNA MIR503HG

图3 Wnt1 mRNA不同表达水平NSCLC患者术后5年生存曲线图中检剔后即为删失。

Fig.3 Five-year survival curve of NSCLC patients with different expression levels of Wnt1 mRNA

表4 不同结局NSCLC患者肺癌组织LncRNA MIR503HG、Wnt1 mRNA表达水平比较（$\bar{x}±s$）

Tab.4 Comparison of lncRNA MIR503HG and Wnt1 mRNA expression levels in lung cancer tissue between the survival group and the death group

组别	n	LncRNA MIR503HG	Wnt1 mRNA
生存组	48	0.70±0.14	1.66±0.28
死亡组	60	0.48±0.10	2.06±0.60
t		9.515^＊＊	4.260^＊＊

表5 NSCLC患者术后5年预后的影响因素分析

Tab.5 Analysis of factors influencing prognosis of patients with NSCLC at 5 years after surgery

变量	β	SE	Wald χ²	P	HR（95%CI）
LncRNA MIR503HG	0.633	0.214	8.749	0.003	1.883（1.238~2.865）
Wnt1 mRNA	0.841	0.360	5.454	0.020	2.318（1.145~4.694）
病理分级	1.288	0.225	32.748	0.004	3.624（2.332~5.633）
TNM分期	1.147	0.328	12.230	<0.001	3.149（1.656~5.989）
淋巴结转移	1.354	0.416	10.586	0.001	3.871（1.713~8.748）

图4 肺癌组织LncRNA MIR503HG、Wnt1 mRNA及二者联合预测NSCLC患者术后5年内生存的ROC曲线

Fig.4 ROC curves of lncRNA MIR503HG, Wnt1 mRNA and their combination in predicting postoperative survival of NSCLC patients within 5 years

表6 肺癌组织LncRNA MIR503HG、Wnt1 mRNA及二者联合对NSCLC患者术后5年内生存的预测价值

Tab.6 Predictive value of lncRNA MIR503HG, Wnt1 mRNA in lung cancer tissue and their combination in predicting 5-year survival of NSCLC patients after surgery

指标	截断值	AUC（95%CI）	敏感度/%	特异度/%	约登指数
LncRNA MIR503HG	0.65	0.823（0.739~0.889）	75.93	84.21	0.601
Wnt1 mRNA	1.74	0.728（0.636~0.808）	72.22	66.67	0.389
联合		0.885（0.810~0.937）	88.49	72.63	0.611

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非小细胞肺癌组织LncRNA MIR503HG、Wnt1表达与患者术后5年内生存的相关性

The correlation between expression of lncRNA MIR503HG and Wnt1 in non-small cell lung cancer tissue and patient survival within 5 years after surgery

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