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中华临床医师杂志(电子版)

中华临床医师杂志(电子版) ›› 2022, Vol. 16 ›› Issue (01) : 77 -83. doi: 10.3877/cma.j.issn.1674-0785.2022.01.014

临床研究

结肠癌组织中lncRNA TPT1-AS1、miR-30c-5p的表达及与病理特征、预后的关系
范子冰1, 时菁1, 刘鸿鹏2, 石雨松2, 秦颖2,†()   
  1. 1. 518029　广东深圳，深圳大学附属第一医院（深圳市第二人民医院）普通外科
    2. 518029　广东深圳，深圳大学附属第一医院（深圳市第二人民医院）胃肠外科
  • 收稿日期:2021-05-20 出版日期:2022-01-15
  • 通信作者: 秦颖
  • 基金资助:
    省部共建肿瘤化学基因组学国家重点实验室开放基金项目(SKLC0202004)

Relationship of expression of lncRNA TPT1-AS1 and miR-30c-5p with pathological characteristics and prognosis in colon cancer

Zibing Fan1, Jing Shi1, Hongpeng Liu2, Yusong Shi2, Ying Qin2,†()   

  1. 1. Department of General Surgery, the First Affiliated Hospital of Shenzhen University (Shenzhen Second People's Hospital), Shenzhen 518029, China
    2. Department of Gastrointestinal Surgery, the First Affiliated Hospital of Shenzhen University (Shenzhen Second People's Hospital), Shenzhen 518029, China
  • Received:2021-05-20 Published:2022-01-15
  • Corresponding author: Ying Qin
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引用本文：

范子冰, 时菁, 刘鸿鹏, 石雨松, 秦颖. 结肠癌组织中lncRNA TPT1-AS1、miR-30c-5p的表达及与病理特征、预后的关系[J/OL]. 中华临床医师杂志(电子版), 2022, 16(01): 77-83.

Zibing Fan, Jing Shi, Hongpeng Liu, Yusong Shi, Ying Qin. Relationship of expression of lncRNA TPT1-AS1 and miR-30c-5p with pathological characteristics and prognosis in colon cancer[J/OL]. Chinese Journal of Clinicians(Electronic Edition), 2022, 16(01): 77-83.

目的

探讨结肠癌组织中长链非编码RNA（lncRNA）肿瘤蛋白翻译调节因子1（TPT1）-反义RNA1（AS1）、微小RNA（miR）-30c-5p的表达及与病理特征、预后的关系。

方法

选取2015年1月至2017年12月深圳大学附属第一医院收治的117例接受根治性或姑息性手术切除结肠癌患者，均行手术切除结肠癌组织及癌旁组织。采用qRT-PCR检测lncRNA TPT1-AS1、miR-30c-5p表达水平，分析lncRNA TPT1-AS1、miR-30c-5p表达水平与结肠癌病理特征的关系，采用Pearson相关性检验分析结肠癌组织中lncRNA TPT1-AS1与miR-30c-5p表达水平的相关性，Kaplan-Meier曲线绘制不同lncRNA TPT1-AS1、miR-30c-5p表达水平结肠癌患者3年累积生存率，Cox回归分析结肠癌患者预后影响因素。

结果

结肠癌组织中lncRNA TPT1-AS1表达水平明显高于癌旁组织（3.405±0.555 vs 1.766±0.096），miR-30c-5p表达水平（0.306±0.146 vs 0.872±0.267）明显低于癌旁组织（P＜0.05）。结肠癌lncRNA TPT1-AS1表达水平TNM分期Ⅲ~Ⅳ期明显高于Ⅰ~Ⅱ期（3.651±0.579 vs 3.257±0.486），浸润深度T3~T4明显高于T1~T2（3.523±0.601 vs 3.301±0.491），有淋巴结转移明显高于无淋巴结转移（3.614±0.585 vs 3.220±0.456），差异均有统计学意义（P＜0.05）；miR-30c-5p表达水平TNM分期Ⅲ~Ⅳ期明显低于Ⅰ~Ⅱ期（0.251±0.126 vs 0.346±0.145），浸润深度T3~T4明显低于T1~T2（0.270±0.119 vs 0.338±0.162），有淋巴结转移明显低于无淋巴结转移（0.255±0.125 vs 0.351±0.151），差异均有统计学意义（P＜0.05）。Pearson相关性分析显示，结肠癌组织中lncRNA TPT1-AS1与miR-30c-5p表达水平呈负相关（r=-0.572，P＜0.05）。Kaplan-Meier生存曲线显示，lncRNA TPT1-AS1高表达水平组3年累积生存率明显低于低表达水平组（59.32% vs 87.93%），miR-30c-5p高表达水平组3年累积生存率明显高于低表达水平组（85.00% vs 61.40%）（P＜0.05）。多因素Cox回归分析显示，TNM分期Ⅲ~Ⅳ期（HR=2.387，95%CI：1.004~5.671）、淋巴结转移（HR=2.667，95%CI：1.021~6.969）、lncRNA TPT1-AS1≥3.405（HR=2.023，95%CI：1.076~3.803）为结肠癌患者预后独立风险因素，miR-30c-5p≥0.306（HR=0.175，95%CI：0.012~0.423）为独立保护因素（P＜0.05）。

结论

结肠癌组织中lncRNA TPT1-AS1表达显著上调，miR-30c-5p表达显著下调，两者与TNM分期、浸润深度、淋巴结转移相关，为患者预后独立影响因素，可能成为结肠癌预后评估的标志物。

关键词: 结肠癌, 长链非编码RNA, 肿瘤蛋白翻译调节因子1, 反义RNA1, 微小RNA-30c-5p
Objective

To detect the expression of the long non-coding RNA (lncRNA) tumor protein translation regulator 1-antisense RNA1 (TPT1-AS1) and microRNA (miR)-30c-5p in colon cancer, and to analyze its relationship with pathological characteristics and prognosis.

Methods

A total of 117 patients with colon cancer who underwent radical or palliative surgery were selected from January 2015 to December 2017 at the First Affiliated Hospital of Shenzhen University. The colon cancer and adjacent tissues were surgically removed, and the expression levels of lncRNA TPT1-AS1 and miR-30c-5p in these tissues were detected by qRT-PCR. The relationship between the expression levels of lncRNA TPT1-AS1 and miR-30C-5p and the pathological features of colon cancer was analyzed, and the correlation between the expression levels of lncRNA TPT1-AS1 and miR-30C-5p in colon cancer tissues was analyzed by Pearson correlation test. Kaplan-Meier curve was used to calculate the 3-year cumulative survival rate of colon cancer patients with different lncRNA TPT1-AS1 and miR-30C-5P expression levels, and Cox regression analysis was performed to analyze the prognostic factors for colon cancer patients.

Results

The expression level of the lncRNA TPT1-AS1 was significantly higher (3.405±0.555 vs 1.766±0.096) and that of miR-30c-5p was significantly lower (0.306±0.146 vs 0.872±0.267) in colon cancer tissues than in adjacent tissues (P＜0.05). The expression level of the lncRNA TPT1-AS1 was significantly higher in colon cancer TNM stage Ⅲ-Ⅳ than in stage Ⅰ-Ⅱ (3.651±0.579 vs 3.257±0.486), in T3-T4 colon cancer than in T1-T2 (3.523±0.601 vs 3.301±0.491), and in colon cancer with lymph node metastasis than in that without (3.614±0.585 vs 3.220±0.456) (P＜0.05). The expression level of miR-30C-5P was significantly lower in colon cancer TNM stage Ⅲ-Ⅳ than that in stage Ⅰ-Ⅱ (0.251±0.126 vs 0.346±0.145), in T3-T4 colon cancer than in T1-T2 (0.270±0.119 vs 0.338±0.162), and in colon cancer with lymph node metastasis than in that without (0.255±0.125 vs 0.351±0.151) (P＜0.05). Pearson correlation analysis showed that the expression of lncRNA1 TPT1-AS1 was negatively correlated with miR-30C-5P expression in colon cancer tissues (r=-0.572, P＜0.05). Kaplan-Meier survival analysis showed that the 3-year cumulative survival rate (59.32% vs 87.93%) of the group with high lncRNA TPT1-AS1 expression was significantly lower than that of the group with low lncRNA1 TPT1-AS1 expression. The 3-year cumulative survival rate of the group with high miR-30C-5P expression (85.00% vs 61.40%) was significantly higher than that of the group with low miR-30C-5P expression (P＜0.05). Multivariate Cox regression analysis showed that TNM stage Ⅲ-Ⅳ [hazard ratio (HR)=2.387, 95% confidence interval (CI): 1.004-5.671], lymph node metastasis (HR=2.667, 95%CI: 1.021-6.969), and TPT1-AS1≥3.405 (HR=2.023, 95%CI: 1.076-3.803) were independent prognostic risk factors for colon cancer patients, while mir-30C-5p ≥0.306 (HR=0.175, 95%CI: 0.012-0.423) was an independent protective factor (P＜0.05).

Conclusion

The expression of lncRNA1 TPT1-AS1 in colon cancer tissue is significantly up-regulated, and the expression of miR-30c-5p is significantly down-regulated, both of which are associated with TNM stage, depth of invasion and lymph node metastasis, are independent prognostic factors for patients, and may become markers for prognostic evaluation of colon cancer.

Key words: Colon cancer, Long non-coding RNA, Tumor protein translation regulator 1, Antisense RNA1, MicroRNA-30c-5p
表1 结肠癌组织与癌旁组织中lncRNA TPT1-AS1、miR-30c-5p表达水平比较（
xˉ
±s）
组别 例数 lncRNA TPT1-AS1 miR-30c-5p
结肠癌 117 3.405±0.555 0.306±0.146
癌旁组织 117 1.766±0.096 0.872±0.267
t值 31.517 -20.076
P值 ＜0.001 ＜0.001
表2 lncRNA TPT1-AS1、miR-30c-5p表达水平与结肠癌病理特征的关系（
xˉ
±s）
病理特征 例数 lncRNA TPT1-AS1 miR-30c-5
性别

男

 69 3.395±0.561 0.321±0.151

女

 48 3.420±0.550 0.285±0.140

t值

 -0.236 1.321

P值

 0.814 0.189
年龄（岁）

≥60

 56 3.475±0.560 0.284±0.131

＜60

 61 3.341±0.546 0.327±0.158

t值

 1.305 -1.595

P值

 0.195 0.114
肿瘤直径（cm）

≥5

 52 3.468±0.581 0.280±0.133

＜5

 65 3.355±0.532 0.327±0.154

t值

 1.091 -1.761

P值

 0.278 0.081
分化程度

低或未分化

 47 3.475±0.605 0.282±0.136

中或高分化

 70 3.358±0.517 0.322±0.152

t值

 1.111 -1.465

P值

 0.269 0.146
TNM分期（期）

Ⅰ~Ⅱ

 73 3.257±0.486 0.346±0.145

Ⅲ~Ⅳ

 44 3.651±0.579 0.251±0.126

t值

 -3.944 3.982

P值

 ＜0.001 ＜0.001
浸润深度

T1~T2

 62 3.301±0.491 0.338±0.162

T3~T4

 55 3.523±0.601 0.270±0.119

t值

 -2.205 2.577

P值

 0.029 0.011
淋巴结转移

有

 55 3.614±0.585 0.255±0.125

无

 62 3.220±0.456 0.351±0.151

t值

 4.096 -3.722

P值

 ＜0.001 ＜0.001
图1 结肠癌组织中lncRNA TPT1-AS1与miR-30c-5p表达水平的线性散点图
图2 不同lncRNA TPT1-AS1、miR-30c-5p表达水平结肠癌患者3年累积生存曲线。图2a为lncRNA TPT1-AS1；图2b为miR-30c-5p
表3 自变量和因变量赋值
变量 赋值
自变量

性别

 男性=1，女性=0

年龄

 ≥60岁=1，＜60岁=0

肿瘤直径

 ≥5 cm为=1，＜5 cm=0

分化程度

 低或未分化为=1，中或高分化=0

TNM分期

 Ⅲ~Ⅳ期=1，Ⅰ~Ⅱ期=0

浸润深度

 T3~T4=1，T1~T2=0

淋巴结转移

 有=1，无=0

lncRNA TPT1-AS1

 ≥3.405=1，＜3.405=0

miR-30c-5p

 ≥0.306=1，＜0.306=0
因变量

预后

 死亡=1，存活=0
表4 结肠癌患者预后影响因素的单因素Cox回归分析
变量 回归系数 标准误 Wald χ2值 P值 HR值 95%CI
男性 -0.064 0.370 0.030 0.863 0.938 0.454~1.939
年龄≥60岁 0.746 0.386 3.728 0.054 2.109 0.989~4.498
肿瘤直径≥5 cm 0.346 0.360 0.923 0.337 1.413 0.698~2.862
低或未分化 0.338 0.360 0.883 0.348 1.402 0.693~2.837
TNM Ⅲ~Ⅳ期 1.270 0.411 9.562 0.002 3.561 1.592~7.964
浸润深度T3~T4 1.051 0.385 7.461 0.006 2.860 1.346~6.080
淋巴结转移 1.452 0.456 10.148 0.001 4.272 1.748~10.438
lncRNA TPT1-AS1≥3.405 1.235 0.268 21.247 ＜0.001 3.437 2.033~5.810
miR-30c-5p≥0.306 -3.282 1.336 6.035 0.014 0.038 0.003~0.515
表5 结肠癌患者预后影响因素的多因素Cox回归分析
变量 回归系数 标准误 Waldχ2值 P值 HR值 95%CI
TNM分期Ⅲ~Ⅳ期 0.870 0.441 3.879 0.049 2.387 1.004~5.671
浸润深度T3~T4 0.231 0.451 0.263 0.608 1.260 1.021~3.049
淋巴结转移 0.981 0.490 4.316 0.038 2.667 1.021~6.969
lncRNA TPT1-AS1≥3.405 0.705 0.322 4.955 0.026 2.023 1.076~3.803
miR-30c-5p≥0.306 -1.743 1.361 4.009 0.045 0.175 0.012~0.423
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