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中华消化病与影像杂志(电子版) ›› 2023, Vol. 13 ›› Issue (03) : 139 -144. doi: 10.3877/cma.j.issn.2095-2015.2023.03.003

论著

LncRNA SNHG4表达与结直肠癌预后的关系
王健, 赵海剑, 孙静, 张晓雨, 陈柏羽†()   
  1. 223002　江苏省，徐州医科大学附属淮安医院/淮安市第二人民医院胃肠外科
    214023　江苏省，南京医科大学附属无锡市人民医院消化内科
    223499　江苏淮安，南京医科大学康达学院附属涟水医院胃肠外科
  • 收稿日期:2023-01-10 出版日期:2023-06-01
  • 通信作者: 陈柏羽
  • 基金资助:
    国家自然科学基金(81800490); 江苏省六大人才高峰工程(WSW-220); 江苏省333高层次人才培养工程(BRA2017247)

Relationship between LncRNA SNHG4 expression and prognosis of colorectal cancer

Jian Wang, Haijian Zhao, Jing Sun, Xiaoyu Zhang, Baiyu Chen†()   

  1. Department of Gastrointestinal Surgery, The Affiliated Huai′an Hospital of Xuzhou Medical University/Huai′an Second People′s Hospital, Huai′an 223002, China
    Department of Gastroenterology, Affiliated Wuxi People′s Hospital of Nanjing Medical University, Wuxi 214023, China
    Department of Gastrointestinal Surgery, Lianshui Hospital Affiliated to Kangda College, Nanjing Medical University, Huai′an 223499, China
  • Received:2023-01-10 Published:2023-06-01
  • Corresponding author: Baiyu Chen
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引用本文：

王健, 赵海剑, 孙静, 张晓雨, 陈柏羽. LncRNA SNHG4表达与结直肠癌预后的关系[J/OL]. 中华消化病与影像杂志(电子版), 2023, 13(03): 139-144.

Jian Wang, Haijian Zhao, Jing Sun, Xiaoyu Zhang, Baiyu Chen. Relationship between LncRNA SNHG4 expression and prognosis of colorectal cancer[J/OL]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2023, 13(03): 139-144.

目的

探讨长链非编码RNA(LncRNA)小核仁RNA宿主基因4(SNHG4)在结直肠癌患者肿瘤组织和癌旁对照组织中的相对表达水平差异和患者临床病理特征及预后之间的关系。

方法

收集2016年6月至2020年12月淮安市第二人民医院80例结直肠癌手术患者的临床病理特征及预后信息。采用实时荧光定量PCR方法，检测肿瘤组织和癌旁对照组织标本中LncRNA SNHG4的相对表达量。

结果

80例结直肠癌患者中有66例患者的癌组织中LncRNA SNHG4表达高于癌旁对照组织，高表达率为82.50%。癌组织中LncRNA SNHG4相对表达量是癌旁对照组织的3.774倍，差异有统计学意义(t＝8.643，P<0.01)。根据LncRNA SNHG4相对表达量中位数值将患者分为高表达组和低表达组，每组各40例。LncRNA SNHG4表达水平与患者的肿瘤T分期、淋巴结转移状态、TNM分期、血浆癌胚抗原水平、组织分化程度高度相关。生存分析结果表明LncRNA SNHG4高表达组5年OS显著低于低表达组患者(χ2＝4.876，P＝0.027)。COX模型单因素变量分析显示TNM分期、肿瘤浸润层次、LncRNA SNHG4表达水平、肿瘤组织分化程度与结直肠癌患者的OS密切相关。COX多因素分析显示肿瘤TNM分期(Ⅲ/Ⅳ期vs Ⅰ/Ⅱ期)(HR＝3.702，95% CI 1.096~12.502，P＝0.035)是结直肠癌患者总生存期的独立影响因子。

结论

结直肠癌患者LncRNA SNHG4表达增加，并且LncRNA SNHG4与恶性病理特征有关。LncRNA SNHG4可促进结直肠癌的进展和转移，影响生存和预后，可作为监测结直肠癌进展和预后的生物学标志物。

关键词: 结直肠癌, 长链非编码RNA, 小核仁RNA宿主基因4, 预后
Objective

To explore the relationships between the relative expression levels of long non-coding RNA(LncRNA)small nucleolar RNA host gene 4(SNHG4)in colorectal cancer tissues and adjacent normal tissues and the clinicopathological characteristics and prognosis of patients.

Methods

The clinicopathological characteristics and prognosis data of 80 colorectal cancerpatients in Huai′an Second People′s Hospital from June 2016 to December 2020 were collected.The relative expressions of LncRNA SNHG4 in cancer tissues and adjacent normal tissues were detected by real-time fluorescence quantitative PCR.

Results

The expressions of LncRNA SNHG4 in 66 cancer tissues were higher than those in corresponding adjacent normal tissues, with the high expression rate of 82.50%.The expression of LncRNA SNHG4 in cancer tissues was 3.774 times higher than that in corresponding adjacent normal tissues, with a statistically significant difference(t=8.643, P<0.01).The patients were divided into high expression group and low expression group according to the median of the relative expression of LncRNA SNHG4, with 40 cases in each group.The expression level of LncRNA SNHG4 was highly correlated with the tumor T stage, lymph node metastasis status, TNM stage, plasma carcinoembryonic antigenlevel, and the degree of tissue differentiation of the patients.Survival analysis showed that the 5-year OS rate of the LncRNA high expression group was significantly lower than that of the low expression group(χ2=4.876, P=0.027).COX univariate analysis showed that TNM stage, level of tumor invasion, LncRNA SNHG4 expression level, and degree of tumor tissue differentiation were related to OS of colorectal cancer patients.COX multivariate analysis showed that tumor TNM stage(stage Ⅲ/Ⅳ vs.stage Ⅰ/Ⅱ)(HR=3.702, 95% CI: 1.096~12.502, P=0.035)was an independent risk factor of OS of colorectal cancer patients.

Conclusion

The expression of LncRNA SNHG4 increases in colorectal cancer patients.LncRNA SNHG4 is related to the malignant pathological characteristics.LncRNA SNHG4 can promote the progression and metastasis of colorectal cancer, and affect the survival and prognosis.It can be used as a biological marker to monitor the progression and prognosis of colorectal cancer.

Key words: Colorectal cancer, Long non-coding RNA, Small nucleolar RNA host gene 4, Prognosis
图1 LncRNA SNHG4在结直肠癌癌组织与癌旁组织表达水平比较(－△△CT)注：80例结直肠癌患者癌组织中IncRNA SNHG4表达量高于癌旁正常组织者达66例，高表达率为82.50%
图2 LncRNA SNHG4在结直肠癌癌组织和癌旁对照组织中表达量的差异倍数(将癌旁对照组织标准化值设为1)注：癌组织中LncRNA SNHG4表达是癌旁对照组织的3.774倍，差异有统计学意义(t＝8.643，P<0.01)
表1 SNHG4表达与结直肠癌临床病理特征之间的关系
临床特征 高表达 低表达 χ2值 P值
性别        
男 24 20 0.808 0.369
女 16 20    
年龄        
≤60岁 21 18 0.450 0.502
>60岁 19 22    
肿瘤最大径        
≥5 cm 24 25 0.053 0.818
<5 cm 16 15    
浸润层次        
T1/2 12 26 9.825 0.002
T3/4 28 14    
分化程度        
G1 9 17 7.192 0.005
G2 17 18    
G3 14 5    
淋巴结转移状态        
有 29 7 24.444 0.000
无 11 33    
TNM分期        
Ⅰ/Ⅱ期 14 30 11.314 0.001
Ⅲ/Ⅳ期 26 10    
癌胚抗原        
>5 ng/mL 28 9 18.152 0.000
≤5 ng/mL 12 31    
远处转移        
M0 35 40 － 0.055
M1 5 0    
合并肠道息肉        
有 22 21 0.050 0.823
无 18 19    
图3 结直肠癌患者5年总生存时间的K－M生存曲线注：IncRNA SNHG4高表达患者5年总生存率为58.8%(20/34)，IncRNA SNHG4低表达组患者5年总生存率81.8%(27/33)，差异有统计学意义(χ2＝4.876，P＝0.027)
表2 结直肠癌术后单因素及多因素Cox回归分析
变量 β SE Wald HR 95% CI P
单变量分析            
SNHG4表达(高vs低) 1.187 0.490 5.877 3.276 1.255~8.552 0.015
性别(男性vs女性) －0.081 0.450 0.032 0.922 0.382~2.227 0.857
年龄(<60岁vs ≥60岁) 0.115 0.448 0.066 1.122 0.467~2.698 0.797
CEA(<5 ng/mL vs ≥5 ng/mL) －0.683 0.457 2.237 0.505 0.206~1.236 0.135
肿瘤位置(结肠vs直肠) －0.003 0.459 0.001 0.997 0.397~2.502 0.995
肿瘤大小(<5 vs ≥5 cm) 0.109 0.457 0.057 1.115 0.455~2.732 0.812
组织学分化(良好/中等vs较差) 1.085 0.455 5.680 2.959 1.213~7.220 0.017
T分期(T1~2 vs T3~4) 1.377 0.497 7.686 3.964 1.497~0.494 0.006
TNM分期(Ⅰ/Ⅱ vs Ⅲ/Ⅳ) 1.729 0.561 9.509 5.632 1.877~6.898 0.002
多变量分析            
SNHG4表达(高vs低) 0.100 0.526 0.036 1.105 0.394~3.096 0.850
组织学分化(良好/中等vs较差) 0.748 0.476 2.469 2.113 0.831~5.372 0.116
T分期(T1~2 vs T3~4) 0.675 0.567 1.414 1.963 0.646~5.970 0.234
TNM分期(Ⅰ/Ⅱ vs Ⅲ/Ⅳ) 1.309 0.621 4.443 3.702 1.096~2.502 0.035
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