长非编码RNA TCF7、LSINCT5在非小细胞肺癌组织中的表达及与预后的关系

doi:10.3760/cma.j.cn371439-20240522-00116

摘要/Abstract

摘要：

目的探究长非编码RNA（lncRNA）TCF7、LSINCT5在非小细胞肺癌（NSCLC）组织的表达及与患者临床病理特征、预后的关系。方法收集2020年6月至2021年10月在武汉科技大学附属孝感医院就诊的108例行单孔胸腔镜根治术治疗的NSCLC患者术中切除的NSCLC组织及癌旁组织标本，实时荧光定量PCR检测lncRNA TCF7、LSINCT5在NSCLC组织及癌旁组织的表达，分析两者表达及与患者临床病理特征的关系，采用Pearson相关分析探讨NSCLC组织中lncRNA TCF7、LSINCT5表达的相关性，Kaplan-Meier法进行生存分析，采用Cox比例风险回归模型分析NSCLC患者预后的影响因素。结果 NSCLC组织中lncRNA TCF7的相对表达量为1.62±0.53，高于癌旁组织的1.08±0.34（t=8.91，P<0.001）；NSCLC组织中lncRNA LSINCT5相对表达量为1.54±0.48，高于癌旁组织的1.07±0.33（t=8.39，P<0.001）。Pearson相关分析显示，lncRNA TCF7、LSINCT5在NSCLC组织中的表达呈正相关（r=0.41，P<0.001）。不同TNM分期（χ²=6.28，P=0.012；χ²=5.40，P=0.020）、组织学分级（χ²=6.31，P=0.012；χ²=7.23，P=0.007）的患者NSCLC组织中lncRNA TCF7、LSINCT5表达差异均具有统计学意义。lncRNA TCF7高表达NSCLC患者（n=54）的术后2年生存率为48.15%，低于低表达患者（n=54）的72.22%（χ²=6.53，P=0.011）；lncRNA LSINCT5高表达NSCLC患者（n=55）的术后2年生存率为47.23%，低于低表达患者（n=53）的73.58%（χ²=7.80，P=0.005）。单因素分析显示，淋巴结转移（HR=1.55，95%CI为1.11~2.17，P=0.011）、TNM分期Ⅲ期（HR=2.15，95%CI为1.32~3.48，P=0.002）、组织学分级低分化（HR=1.39，95%CI为1.11~1.73，P=0.004）、淋巴结状态阳性（HR=1.75，95%CI为1.37~2.23，P<0.001）、肿瘤最大径>2 cm（HR=1.93，95%CI为1.09~3.43，P=0.024）、lncRNA TCF7高表达（≥1.62）（HR=1.77，95%CI为1.41~2.21，P<0.001）、lncRNA LSINCT5高表达（≥1.54）（HR=1.54，95%CI为1.21~1.97，P<0.001）均与行单孔胸腔镜根治术NSCLC患者的预后相关；多因素分析显示，TNM分期Ⅲ期（HR=1.25，95%CI为1.03~1.53，P=0.026）、组织学分级低分化（HR=1.63，95%CI为1.07~2.48，P=0.023）、lncRNA TCF7高表达（HR=1.29，95%CI为1.03~1.62，P=0.025）、lncRNA LSINCT5高表达（HR=1.48，95%CI为1.14~1.93，P=0.004）均为影响NSCLC患者预后的独立危险因素。结论 lncRNA TCF7、LSINCT5在NSCLC组织中表达上调，两者表达呈正相关，两者高表达、TNM分期Ⅲ期、组织学分级低分化的患者预后不良风险高。

关键词: 癌，非小细胞肺, RNA，长链非编码, 预后, TCF7, LSINCT5

Abstract:

Objective To investigate the expression levels of long non-coding RNA （lncRNA） TCF7 and LSINCT5 in non-small cell lung cancer （NSCLC） tissues and the relationship with clinical pathological characteristics and prognosis of patients. Methods NSCLC tissues and para-carcinoma tissues specimens of 108 NSCLC patients who underwent single-port thoracoscopic radical resection at Xiaogan Hospital Affiliated to Wuhan University of Science and Technology from June 2020 to October 2021 were collected. Real-time fluorescence quantitative PCR was applied to detect the expression of lncRNA TCF7 and LSINCT5 in NSCLC tissues and para-carcinoma tissues. The relationship between the expression of both and the clinical and pathological characteristics of patients was analyzed. Pearson correlation analysis was used to explore the correlation between the expression of lncRNA TCF7 and LSINCT5 in NSCLC tissues. Kaplan-Meier method was used for survival analysis. Cox proportional hazard regression model was applied to analyze the influencing factors of prognosis of NSCLC patients. Results The relative expression of lncRNA TCF7 in NSCLC tissues was 1.62±0.53， which was significantly higher than that in para-carcinoma tissues （1.08±0.34， t=8.91， P<0.001）. The relative expression of lncRNA LSINCT5 in NSCLC tissues was 1.54±0.48， which was significantly higher than that in para-carcinoma tissues （1.07±0.33， t=8.39， P<0.001）. Pearson correlation analysis showed that the expression of lncRNA TCF7 and LSINCT5 in NSCLC tissues was positively correlated （r=0.41， P<0.001）. There were statistically significant differences in the expression of lncRNA TCF7 and LSINCT5 in NSCLC tissues among patients with different TNM stages （χ²=6.28， P=0.012； χ²=5.40， P=0.020） and histological grades （χ²=6.31， P=0.012； χ²=7.23， P=0.007）. The 2-year survival rate of NSCLC patients with high expression of lncRNA TCF7 （n=54） was 48.15%， which was significantly lower than that of patients with low expression （n=54）（72.22%， χ²=6.53，P=0.011）. The 2-year survival rate of NSCLC patients with high expression of lncRNA LSINCT5 （n=55） was 47.23%， which was significantly lower than that of patients with low expression （n=53）（73.58%， χ²=7.80， P=0.005）. Univariate analysis showed that lymph node metastasis （HR=1.55， 95%CI： 1.11-2.17， P=0.011）， TNM stage Ⅲ （HR=2.15， 95%CI： 1.32-3.48， P=0.002）， poorly differentiated histologically grade （HR=1.39， 95%CI： 1.11-1.73， P=0.004）， positive lymph node status （HR=1.75， 95%CI： 1.37-2.23， P<0.001）， maximum diameter of tumor >2 cm （HR=1.93， 95%CI： 1.09-3.43， P=0.024）， high expression of lncRNA TCF7 （≥1.62）（HR=1.77， 95%CI： 1.41-2.21， P<0.001）， high expression of lncRNA LSINCT5 （≥1.54）（HR=1.54， 95%CI： 1.21-1.97， P<0.001） were associated with prognosis of NSCLC patients who underwent single-port thoracoscopic radical resection. Multivariate analysis showed that TNM stage Ⅲ （HR=1.25， 95%CI： 1.03-1.53， P=0.026）， poor differentiated histologically grade （HR=1.63， 95%CI： 1.07-2.48， P=0.023）， high expression of lncRNA TCF7 （HR=1.29， 95%CI： 1.03-1.62， P=0.025）， high expression of lncRNA LSINCT5 （HR=1.48， 95%CI： 1.14-1.93， P=0.004） were independent risk factors for prognosis of NSCLC patients. Conclusion The expressions of lncRNA TCF7 and LSINCT5 are up-regulated in NSCLC tissues， and their expressions are positively correlated. Patients with high expression of lncRNA TCF7 and LSINCT5， patients in TNM stage Ⅲ， and patients with poorly differentiated histologically grade have a high risk of poor prognosis.

Key words: Carcinoma， non-small-cell lung, RNA， long non-coding, Prognosis, TCF7, LSINCT5

邱琦, 刘钧, 谢志斌, 邓科兰, 王萌萌. 长非编码RNA TCF7、LSINCT5在非小细胞肺癌组织中的表达及与预后的关系[J]. 国际肿瘤学杂志, 2024, 51(11): 684-689.

Qiu Qi, Liu Jun, Xie Zhibin, Deng Kelan, Wang Mengmeng. Expression of long non-coding RNA TCF7 and LSINCT5 in non-small cell lung cancer tissues and the relationship with prognosis[J]. Journal of International Oncology, 2024, 51(11): 684-689.

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基因	正向引物	反向引物
lncRNA TCF7	5'-ATCATCCTCTCTATCTACCTCTATC-3'	5'-AGCATAGCAAAGGTCAGGGCTCGAA-3'
lncRNA LSINCT5	5'-CCAGCUACAAACCUCUGAATT-3'	5'-UUCAGAGG-UUUGUAGCUGGTT-3'
GAPDH	5'-AGATCCCTCCAAAATCAAGTGG-3'	5'-GGCAGAGATGATGACCCTTTT-3'

因素	单因素分析		多因素分析
因素	HR值（95%CI）	P值	HR值（95%CI）	P值
年龄（≥55岁/<55岁）	1.83（0.72~4.62）	0.203
性别（男/女）	1.64（0.65~4.13）	0.299
浸润深度（>1 cm/≤1 cm）	2.77（0.53~14.46）	0.227
淋巴结转移（有/无）	1.55（1.11~2.17）	0.011	1.57（0.68~3.62）	0.291
TNM分期（Ⅲ期/Ⅰ~Ⅱ期）	2.15（1.32~3.48）	0.002	1.25（1.03~1.53）	0.026
组织学分级（低分化/中高分化）	1.39（1.11~1.73）	0.004	1.63（1.07~2.48）	0.023
淋巴结状态（阳性/阴性）	1.75（1.37~2.23）	<0.001	1.54（0.97~2.46）	0.067
肿瘤最大径（>2 cm/≤2 cm）	1.93（1.09~3.43）	0.024	1.89（0.92~3.90）	0.084
lncRNA TCF7（≥1.62/<1.62）	1.77（1.41~2.21）	<0.001	1.29（1.03~1.62）	0.025
lncRNA LSINCT5（≥1.54/<1.54）	1.54（1.21~1.97）	<0.001	1.48（1.14~1.93）	0.004