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

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:

ObjectiveTo 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.MethodsNSCLC 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.ResultsThe 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.ConclusionThe 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.

图/表6

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'

表1

基因	癌旁组织	NSCLC组织	t值	P值
lncRNA TCF7	1.08±0.34	1.62±0.53	8.91	<0.001
lncRNA LSINCT5	1.07±0.33	1.54±0.48	8.39	<0.001

表2

表3

lncRNA TCF7、LSINCT5在NSCLC组织中的表达与患者临床病理特征的关系（例）"

临床病理特征	例数	TCF7				LSINCT5
临床病理特征	例数	高表达（n=54）	低表达（n=54）	χ²值	P值	高表达（n=55）	低表达（n=53）	χ²值	P值
年龄（岁）
<55	52	29	23	1.34	0.248	24	28	0.91	0.339
≥55	56	25	31	1.34	0.248	31	25	0.91	0.339
性别
男	58	28	30	0.15	0.700	26	32	1.86	0.172
女	50	26	24	0.15	0.700	29	21	1.86	0.172
浸润深度（cm）
≤1	47	24	23	0.04	0.846	25	22	0.17	0.679
>1	61	30	31	0.04	0.846	30	31	0.17	0.679
淋巴结转移
无	43	19	24	0.97	0.326	18	25	2.35	0.125
有	65	35	30	0.97	0.326	37	28	2.35	0.125
TNM分期
Ⅰ~Ⅱ期	57	22	35	6.28	0.012	23	34	5.40	0.020
Ⅲ期	51	32	19	6.28	0.012	32	19	5.40	0.020
组织学分级
中高分化	49	18	31	6.31	0.012	18	31	7.23	0.007
低分化	59	36	23	6.31	0.012	37	22	7.23	0.007
淋巴结状态
阴性	45	18	27	3.09	0.079	19	26	2.34	0.126
阳性	63	36	27	3.09	0.079	36	27	2.34	0.126
肿瘤最大径（cm）
≤2	60	25	35	3.75	0.053	26	34	3.11	0.078
>2	48	29	19	3.75	0.053	29	19	3.11	0.078

表3

图1

图2

表4

影响108例行单孔胸腔镜根治术NSCLC患者预后的单因素和多因素分析"

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

表4

参考文献17

[1]	Jianyong Z, Yanruo H, Xiaoju T, et al. Roles of lipid profiles in human non-small cell lung cancer[J].Technol Cancer Res Treat,2021,20(3): 1530-1538. DOI:10.1177/15330338211041472.
[2]	Wu B, Chen M, Gao M, et al. Down-regulation of lncTCF7 inhibits cell migration and invasion in colorectal cancer via inhibiting TCF7 expression[J].Hum Cell,2019,32(1): 31-40. DOI:10.1007/s13577-018-0217-y. pmid:30225781
[3]	Zhang G, Song W. Long non-coding RNA LSINCT5 inactivates Wnt/β-catenin pathway to regulate MCF-7 cell proliferation and motility through targeting the miR-30a[J].Ann Transl Med,2020,8(24): 1635. DOI:10.21037/atm-20-7253. pmid:33490147
[4]	支修益, 石远凯, 于金明. 中国原发性肺癌诊疗规范(2015年版)[J].中华肿瘤杂志,2015,37(1): 67-78. DOI:10.3760/cma.j.issn.0253-3766.2015.01.014.
[5]	中华医学会, 中华医学会肿瘤学分会, 中华医学会杂志社. 中华医学会肺癌临床诊疗指南(2019版)[J].中华肿瘤杂志,2020,42(4): 257-287. DOI:10.3760/cma.j.cn112152-20200120-00049.
[6]	Majem B, Nadal E, Muñoz-Pinedo C. Exploiting metabolic vulnerabilities of non small cell lung carcinoma[J].Semin Cell Dev Biol,2020,98: 54-62. DOI:10.1016/j.semcdb.2019.06.004. pmid:31238096
[7]	Ganti AK, Klein AB, Cotarla I, et al. Update of incidence, prevalence, survival, and initial treatment in patients with non-small cell lung cancer in the US[J].JAMA Oncol,2021,7(12): 1824-1832. DOI:10.1001/jamaoncol.2021.4932. pmid:34673888
[8]	de Koning HJ, van der Aalst CM, de Jong PA, et al. Reduced lung-cancer mortality with volume CT screening in a randomized trial[J].N Engl J Med,2020,382(6): 503-513. DOI:10.1056/NEJMoa1911793.
[9]	Liu H, Shen Y, Xu Y, et al. lncRNA transcription factor 7 is related to deteriorating clinical features and poor prognosis in multiple myeloma, and its knockdown suppresses disease progression by regulating the miR-203-mediated Jagged1-Notch1 signaling pathway[J].Oncol Lett,2021,21(5): 412. DOI:10.3892/ol.2021.12673.
[10]	Chen YZ, Wang JW, Meng FC, et al. LncRNATCF7 up-regulates DNMT1 mediated by HPV-18 E6 and regulates biological behavior of cervical cancer cells by inhibiting miR-155[J].Eur Rev Med Pharmacol Sci,2019,23(20): 8779-8787. DOI:10.26355/eurrev_201910_19272.
[11]	Ding T, Deng R, Huang T. Long non-coding RNA T cell factor 7 is associated with increased disease risk and poor prognosis, and promotes cell proliferation, attenuates cell apoptosis and miR-200c expression in multiple myeloma[J].Oncol Lett,2021,21(2): 129. DOI:10.3892/ol.2020.12390.
[12]	袁前超, 郑志阳, 齐宇. LncRNA TCF7调节JAK/STAT信号通路对肺癌细胞增殖的影响[J].实用癌症杂志,2022,37(2): 181-185. DOI:10.3969/j.issn.1001-5930.2022.02.002.
[13]	Liu B, Cao W, Ma H. Knockdown of lncRNA LSINCT5 suppresses growth and metastasis of human glioma cells via up-regulating miR-451[J].Artif Cells Nanomed Biotechnol,2019,47(1): 2507-2515. DOI:10.1080/21691401.2019.1626404. pmid:31213092
[14]	熊玮, 刘慧敏, 刘平, 等. lncRNA LSINCT5通过miR-451调控肺癌细胞侵袭、迁移及顺铂敏感性的实验研究[J].中国免疫学杂志,2022,38(11): 1349-1354. DOI:10.3969/j.issn.1000-484X.2022.11.012.
[15]	Yang W, Yang X, Li Q, et al. Long stress-induced non-coding transcript 5: a promising therapeutic target for cancer treatment[J].Adv Clin Exp Med,2023,32(1): 97-106. DOI:10.17219/acem/152705.
[16]	Jiang H, Li Y, Li J, et al. Long noncoding RNA LSINCT5 promotes endometrial carcinoma cell proliferation, cycle, and invasion by promoting the Wnt/β-catenin signaling pathway via HMGA2[J].Ther Adv Med Oncol,2019,11: 1758835919874649. DOI:10.1177/1758835919874649.
[17]	Jing L, Lin J, Zhao Y, et al. Long noncoding RNA LSINCT5 is upregulated and promotes the progression of esophageal squamous cell carcinoma[J].Eur Rev Med Pharmacol Sci,2019,23(12): 5195-5205. DOI:10.26355/eurrev_201906_18184.