结肠癌合并2型糖尿病患者血清lncRNA ANRIL、miR-181b-5p的表达及其与淋巴结转移的相关性

潘勇娜; 康金旺; 常月锋

doi:10.7619/jcmp.20242987

结肠癌合并2型糖尿病患者血清lncRNA ANRIL、miR-181b-5p的表达及其与淋巴结转移的相关性

河北北方学院附属第二医院消化内科, 河北张家口, 075100

基金项目:

河北省卫生健康委员会资助项目 20210473

详细信息

通讯作者:
常月锋

中图分类号: R735.3;R587.1;R319
计量
- 文章访问数: 63
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出版历程
- 收稿日期: 2024-07-15
- 修回日期: 2024-10-27
- 刊出日期: 2025-01-27

Expressions of lncRNA ANRIL and miR-181b-5p in the serum of patients with colon cancer complicated with type 2 diabetes mellitus and their correlations with lymph node metastasis

Department of Gastroenterology, the Second Hospital Affiliated to Hebei North University, Zhangjiakou, Hebei, 075100

摘要

摘要:
目的
探讨结肠癌合并2型糖尿病(T2DM)患者血清长链非编码RNA INK4基因座中反义非编码RNA(lncRNA ANRIL)、微小RNA-181b-5p(miR-181b-5p)的表达及其与淋巴结转移的相关性。
方法
选取2019年5月—2022年8月本院收治的117例结肠癌合并T2DM患者为结肠癌合并T2DM组，并根据患者淋巴结转移情况将其分为淋巴结转移组56例和淋巴结未转移组61例。另选取同期体检的健康志愿者117例为对照组。采用反转录实时定量PCR检测血清lncRNA ANRIL、miR-181b-5p的相对表达水平。采用Logistic回归分析探讨影响结肠癌合并T2DM患者淋巴结转移的因素。绘制受试者工作特征(ROC)曲线分析血清lncRNA ANRIL、miR-181b-5p水平对结肠癌合并T2DM患者淋巴结转移的诊断价值。采用Pearson相关分析探讨结肠癌合并T2DM患者血清lncRNA ANRIL与miR-181b-5p表达的相关性。
结果
与对照组比较，结肠癌合并T2DM组患者血清lncRNA ANRIL水平升高, miR-181b-5p水平降低，差异均有统计学意义(P < 0.01)。与淋巴结未转移组比较，淋巴结转移组患者血清lncRNA ANRIL水平升高, miR-181b-5p水平降低，差异均有统计学意义(P < 0.01)。淋巴结转移组与淋巴结未转移组患者TNM分期、分化程度以及糖化血红蛋白(HbA1C)比较，差异有统计学意义(P < 0.05)。糖尿病史、TNM分期、分化程度、HbA1C以及lncRNA ANRIL均是淋巴结转移的影响因素(P < 0.05), miR-181b-5p是影响淋巴结转移的保护因素(P < 0.05)。血清lncRNA ANRIL与miR-181b-5p水平呈负相关(r=-0.440, P < 0.001)。ROC曲线结果显示, 血清lncRNA ANRIL、miR-181b-5p以及二者联合诊断淋巴结转移的曲线下面积(AUC)分别为0.800、0.837、0.930, 联合诊断价值显著高于lncRNA ANRIL(Z=2.956, P=0.003)、miR-181b-5p(Z=2.117, P=0.034)单独诊断价值。
结论
结肠癌合并T2DM患者血清lncRNA ANRIL水平升高, miR-181b-5p水平降低，且二者与淋巴结转移具有一定相关性。
- 结肠癌 /
- 2型糖尿病 /
- 长链非编码RNA /
- INK4基因座中反义非编码RNA /
- 微小RNA-181b-5p
Abstract:
Objective
To investigate the expressions of long non-coding RNA antisense non-coding RNA in the INK4 locus (lncRNA ANRIL) and microRNA-181b-5p (miR-181b-5p) in the serum of patients with colon cancer complicated with type 2 diabetes mellitus (T2DM) and their correlations with lymph node metastasis.
Methods
A total of 117 patients with colon cancer complicated with T2DM in the hospital from May 2019 to August 2022 were selected as colon cancer with T2DM group and divided into lymph node metastasis group (n=56) and no lymph node metastasis group (n=61) according to the lymph node metastasis status. Additionally, 117 healthy volunteers with physical examinations in the same period were selected as control group. Reverse transcription real-time quantitative PCR was used to detect the relative expression levels of serum lncRNA ANRIL and miR-181b-5p. Logistic regression analysis was conducted to explore the factors influencing lymph node metastasis in patients with colon cancer complicated with T2DM. Receiver operating characteristic (ROC) curve was plotted to analyze the diagnostic values of serum lncRNA ANRIL and miR-181b-5p levels for lymph node metastasis in patients with colon cancer complicated with T2DM. Pearson correlation analysis was used to investigate the correlation between serum lncRNA ANRIL and miR-181b-5p expression in patients with colon cancer complicated with T2DM.
Results
Compared with the control group, patients in the colon cancer with T2DM group had significant increased serum lncRNA ANRIL level and decreased miR-181b-5p level (P < 0.01). Compared with the no lymph node metastasis group, patients in the lymph node metastasis group had significant increased serum lncRNA ANRIL level and decreased miR-181b-5p level (P < 0.01). There were significant differences in TNM stage, degree of differentiation, and glycated hemoglobin (HbA1C) between the lymph node metastasis group and the no lymph node metastasis group (P < 0.05). History of diabetes, TNM stage, degree of differentiation, HbA1C, and lncRNA ANRIL were influencing factors for lymph node metastasis (P < 0.05), while miR-181b-5p was a protective factor against lymph node metastasis (P < 0.05). There was a negative correlation between serum lncRNA ANRIL and miR-181b-5p levels (r=-0.440, P < 0.001). The ROC curve result showed that the areas under the curve (AUCs) for the diagnosis of lymph node metastasis by serum lncRNA ANRIL, miR-181b-5p, and their combination were 0.800, 0.837 and 0.930 respectively. The combined diagnostic value was significantly higher than that of lncRNA ANRIL (Z=2.956, P=0.003) and miR-181b-5p (Z=2.117, P=0.034) alone.
Conclusion
Patients with colon cancer complicated with T2DM have increased serum lncRNA ANRIL level and decreased miR-181b-5p level, and both two indexes are correlated with lymph node metastasis.
- colon cancer /
- type 2 diabetes mellitus /
- long non-coding RNA /
- antisense non-coding RNA in the INK4 locus /
- microRNA-181b-5p

HTML全文

图 1 血清lncRNA ANRIL与miR-181b-5p的相关性

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图 2 血清lncRNA ANRIL、miR-181b-5p水平对结肠癌合并T2DM患者淋巴结转移的诊断价值

下载: 全尺寸图片幻灯片

表 1 引物序列

引物名称	上游	下游
lncRNA ANRIL	5′-CCCCTCGTCGAAAGTCTTCCATTC-3′	5′-TTGGCGGATAGAGCAATGAGAT-GAC-3′
GADPH	5′-CACCATTGGCAATGAGCGGTTC-3′	5′-AG-GTCTTTGCGGATGTCCACGT-3′
miR-181b-5p	5′-CACGACACCAACATTCATTGC-3′	5′-CACGACACCAACATTCATTGC-3′
U6	5′-CAGCACATATACTAAAATTGGAACG-3′	5′-CAGCACATATACTAAAATTGGAACG-3′

下载: 导出CSV

表 2 2组血清lncRNA ANRIL、miR-181b-5p水平比较(x±s)

组别	lncRNA ANRIL	miR-181b-5p
对照组(n=117)	1.02±0.10	1.00±0.11
结肠癌合并T2DM组(n=117)	1.24±0.16^**	0.71±0.08^**
与对照组比较, * * P < 0.01。

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表 3 淋巴结转移组与淋巴结未转移组血清lncRNA ANRIL、miR-181b-5p水平比较(x±s)

组别	lncRNA ANRIL	miR-181b-5p
淋巴结转移组(n=56)	1.38±0.19	0.65±0.07
淋巴结未转移组(n=61)	1.12±0.13^**	0.77±0.08^**
与淋巴结转移组比较, * * P < 0.01。

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表 4 淋巴结转移组与淋巴结未转移组临床病理特征分析(x±s)[n(%)]

指标	分类	淋巴结转移组(n=56)	淋巴结未转移组(n=61)	χ²/t	P
年龄	>55岁	32(57.14)	30(49.18)	0.743	0.389
	≤55岁	24(42.86)	31(50.82)
性别	男	29(51.79)	33(54.10)	0.063	0.802
	女	27(48.21)	28(45.90)
糖尿病史	>3年	30(53.57)	25(40.98)	1.857	0.173
	≤3年	26(46.43)	36(59.02)
TNM分期	Ⅰ~Ⅱ期	26(46.43)	40(65.57)	4.352	0.037
	Ⅲ~Ⅳ期	30(53.57)	21(34.43)
分化程度	低分化	36(64.29)	25(40.98)	6.353	0.012
	高分化	20(35.71)	36(59.02)
空腹血糖/(mmol/L)		8.96±2.11	8.38±1.31	1.802	0.074
餐后2 h血糖/(mmol/L)		12.36±2.98	11.82±2.55	1.056	0.293
糖化血红蛋白/%		8.51±1.68	7.72±1.34	2.823	0.006

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表 5 Logistic回归分析结肠癌合并T2DM患者淋巴结转移的影响因素

自变量	B	SE	Wald	P	OR	95%CI
TNM分期	0.755	0.302	6.253	0.012	2.128	1.177~3.846
分化程度	0.857	0.346	6.128	0.013	2.355	1.195~4.640
HbA1C	0.674	0.215	9.841	0.002	1.963	1.287~2.992
lncRNA ANRIL	0.631	0.221	8.159	0.004	1.880	1.219~2.899
miR-181b-5p	-0.564	0.186	9.191	0.002	0.569	0.395~0.819

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表 6 血清lncRNA ANRIL、miR-181b-5p水平对结肠癌合并T2DM患者淋巴结转移的诊断价值

指标	AUC	灵敏度/%	特异度/%	截断值	约登指数	95%CI
lncRNA ANRIL	0.800	75.00	82.93	1.25	0.579	0.693~0.883
miR-181b-5p	0.837	94.44	60.98	0.74	0.554	0.735~0.911
二者联合	0.930	91.67	87.80	—	0.795	0.849~0.976

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