结直肠癌组织LncRNA LINC00342和miR-203a-3p表达及与预后的关系

doi:10.11958/20231812

摘要/Abstract

摘要：

目的分析结直肠癌组织长链非编码RNA（LncRNA）LINC00342、微小RNA-203a-3p（miR-203a-3p）表达水平与患者术后5年内预后的关系。方法采集133例结直肠癌患者的结直肠癌组织及癌旁组织。荧光定量PCR法检测LncRNA LINC00342和miR-203a-3p表达；术后随访5年记录患者生存和死亡情况。比较不同情况下LncRNA LINC00342、miR-203a-3p表达及临床病理参数。分析结直肠癌组织中LncRNA LINC00342、miR-203a-3p表达的相关性、与预后的关系及对预后的预测价值。结果结直肠癌组织中LncRNA LINC00342表达水平高于癌旁组织，miR-203a-3p表达水平低于癌旁组织（P<0.05）。结直肠癌组织中LncRNA LINC00342与miR-203a-3p表达水平呈负相关（P<0.05）。LncRNA LINC00342高表达组、miR-203a-3p低表达组肿瘤低分化、TNMⅢ期、有淋巴结转移患者比例分别高于LncRNA LINC00342低表达组和miR-203a-3p高表达组（P<0.05）。LncRNA LINC00342高表达组、miR-203a-3p低表达组术后5年总生存率更低（P<0.05）。死亡组肿瘤低分化、TNMⅢ期、有淋巴结转移患者比例、LncRNA LINC00342表达水平高于存活组，miR-203a-3p表达水平低于存活组（P<0.05）。肿瘤低分化、TNMⅢ期、有淋巴结转移、LncRNA LINC00342高表达、miR-203a-3p低表达是影响患者术后5年内死亡的独立危险因素（P<0.05）。LncRNA LINC00342和miR-203a-3p联合对预后的预测价值高于单独预测。结论结直肠癌组织中LncRNA LINC00342呈高表达，miR-203a-3p呈低表达，二者联合检测有望成为预测术后生存的临床评估指标。

关键词: 结直肠肿瘤, RNA，长链非编码, 预后, 长链非编码RNA LINC00342, 微小RNA-203a-3p

Abstract:

Objective To analyze the relationship between expression levels of long non-coding RNA (LncRNA) LINC00342 and microRNA-203a-3p (miR-203a-3p) in colorectal cancer tissue and the prognosis of patients within 5 years after surgery. Methods Samples of colorectal cancer tissue and paracancer tissue of 133 patients with colorectal cancer were collected. Expression levels of LncRNA LINC00342 and miR-203a-3p were detected by fluorescence quantitative PCR. Survival and death were recorded after 5 years of follow-up. The LncRNA LINC00342 and miR-203a-3p expressions and clinicopathological parameters in patients under different conditions were compared. The correlation between expressions of LncRNA LINC00342 and miR-203a-3p in colorectal cancer tissue was analyzed, and their predictive value for the prognosis was also analyzed. Results The expression level of LncRNA LINC00342 was higher in colorectal cancer tissue than that in paracancer tissue, and the expression level of miR-203a-3p was lower in colorectal cancer tissue than that in paracancer tissue (P<0.05). The expression levels of LncRNA LINC00342 and miR-203a-3p in colorectal cancer tissue were negatively correlated (P<0.05). The proportion of patients with low tumor differentiation, TNM stage Ⅲ and lymph node metastasis were higher in the LncRNA LINC00342 high expression group and the miR-203a-3p low expression group than those in the LncRNA LINC00342 low expression group and the miR-203a-3p high expression group, respectively (P<0.05). The 5-year overall survival rate after operation was lower in the LncRNA LINC00342 high expression group and the miR-203a-3p low expression group (P<0.05). The proportion of patients with low tumor differentiation, TNM stage Ⅲ, lymph node metastasis, and higher expression level of LncRNA LINC00342 were higher in colorectal cancer tissue of the death group than those in the survival group, and the expression level of miR-203a-3p was lower than that in the survival group (P<0.05). Low tumor differentiation, TNM stage Ⅲ, lymph node metastasis, high expression of LncRNA LINC00342 and low expression of miR-203a-3p were independent risk factors for death within 5 years after colorectal cancer surgery (P<0.05). The combined predictive value of LncRNA LINC00342 and miR-203a-3p for prognosis was greater than that of individual prediction. Conclusion LncRNA LINC00342 is higher expressed and miR-203a-3p is lower expressed in colorectal cancer tissue, and the combined detection of the two is expected to become a clinical evaluation indicator for predicting postoperative survival.

Key words: colorectal neoplasms, RNA, long noncoding, prognosis, LncRNA LINC00342, miR-203a-3p

中图分类号:

R735.34

图/表 8

参考文献 21

[1]	MORGAN E, ARNOLD M, GINI A, et al. Global burden of colorectal cancer in 2020 and 2040:incidence and mortality estimates from GLOBOCAN[J]. Gut, 2023, 72(2):338-344. doi:10.1136/gutjnl-2022-327736.
[2]	ZORZI M, URSO E D L. Impact of colorectal cancer screening on incidence,mortality and surgery rates:evidences from programs based on the fecal immunochemical test in Italy[J]. Dig Liver Dis, 2023, 55(3):336-341. doi:10.1016/j.dld.2022.08.013.
[3]	JOHN KENNETH M, TSAI H C, FANG C Y, et al. Diet-mediated gut microbial community modulation and signature metabolites as potential biomarkers for early diagnosis,prognosis,prevention and stage-specific treatment of colorectal cancer[J]. J Adv Res, 2023, 52(1):45-57. doi:10.1016/j.jare.2022.12.015.
[4]	CARDOSO R, GUO F, HEISSER T, et al. Colorectal cancer incidence,mortality,and stage distribution in European countries in the colorectal cancer screening era:an international population-based study[J]. Lancet Oncol, 2021, 22(7):1002-1013. doi:10.1016/S1470-2045(21)00199-6.
[5]	ZHANG X, MA D, XUAN B, et al. LncRNA CACClnc promotes chemoresistance of colorectal cancer by modulating alternative splicing of RAD51[J]. Oncogene, 2023, 42(17):1374-1391. doi:10.1038/s41388-023-02657-y.
[6]	OLATUBOSUN M O, ABUBAKAR M B, BATIHA G E, et al. LncRNA SNHG15:a potential therapeutic target in the treatment of colorectal cancer[J]. Chem Biol Drug Des, 2023, 101(5):1138-1150. doi:10.1111/cbdd.14036.
[7]	SU H, YU S, SUN F, et al. LINC00342 induces metastasis of lung adenocarcinoma by targeting miR-15b/TPBG[J]. Acta Biochim Pol, 2022, 69(2):291-297. doi:10.18388/abp.2020_5697.
[8]	MIAO R, YAO Z, HU B, et al. A novel long non-coding RNA XLOC_004787,is associated with migration and promotes cancer cell proliferation by downregulating miR-203a-3p in gastric cancer[J]. BMC Gastroenterol, 2023, 23(1):280-293. doi:10.1186/s12876-023-02912-2.
[9]	CHEN Q F, KONG J L, ZOU S C, et al. LncRNA LINC00342 regulated cell growth and metastasis in non-small cell lung cancer via targeting miR-203a-3p[J]. Eur Rev Med Pharmacol Sci, 2019, 23(17):7408-7418. doi:10.26355/eurrev_201909_18849.
[10]	中华人民共和国卫生和计划生育委员会医政医管局, 中华医学会肿瘤学分会. 中国结直肠癌诊疗规范(2017年版)[J]. 中华外科杂志, 2018, 56(4):241-258.
	Hospital Authority of National Health and Family Planning Commission of the People's Republic of China,Chinese Society of Oncology. Chinese protocol of diagnosis and treatment of colorectal cancer(2017 edition)[J]. Chin J Surg, 2018, 56(4):241-258. doi:10.3760/cma.j.issn.0529-5815.2018.04.001.
[11]	BREEKVELDT E C H, LANSDORP-VOGELAAR I, TOES-ZOUTENDIJK E, et al. Colorectal cancer incidence,mortality,tumour characteristics,and treatment before and after introduction of the faecal immunochemical testing-based screening programme in the Netherlands:a population-based study[J]. Lancet Gastroenterol Hepatol, 2022, 7(1):60-68. doi:10.1016/S2468-1253(21)00368-X.
[12]	GUO L, WANG Y, YANG W, et al. Molecular profiling provides clinical insights into targeted and immunotherapies as well as colorectal cancer prognosis[J]. Gastroenterology, 2023, 165(2):414-428. doi:10.1053/j.gastro.2023.04.029.
[13]	姜辉, 孙志涛, 张宝玉, 等. 结直肠癌患者血清微小RNA-615-5p和音猬因子表达与临床病理特征及预后的关系[J]. 中国中西医结合外科杂志, 2023, 29(2):204-210.
	JIANG H, SUN Z T, ZHANG B Y, et al. Correlation of serum micro RNA-615-5p and SHH expression with clinicopathological features and prognosis in patients with colorectal cancer[J]. Chinese Journal of Surgery of Integrated Traditional and Western Medicine, 2023, 29(2):204-210. doi:10.3969/j.issn.1007-6948.2023.02.013..
[14]	PENG H, YING J, ZANG J, et al. Specific mutations in APC,with prognostic implications in metastatic colorectal cancer[J]. Cancer Res Treat, 2023, 55(4):1270-1280. doi:10.4143/crt.2023.415.
[15]	ZHAO F, WANG M, ZHANG Y, et al. LncRNA PSMB8-AS1 promotes colorectal cancer progression through sponging miR-1299 to upregulate ADAMTS5[J]. Neoplasma, 2022, 69(5):1138-1153. doi:10.4149/neo_2022_220111N42.
[16]	郭莹叶. LINC00342/miR-505-3p/PGK1基因在乳腺癌患者肿瘤转移中的表达以及对细胞生物学特性的影响[J]. 中国细胞生物学学报, 2023, 45(2):193-202.
	GUO Y Y. The Expression of LINC00342/miR-505-3p/PGK1 gene expression in breast cancer patients with tumor metastasis and its influence on cell biological characteristics[J]. Chinese Journal of Cell Biology, 2023, 45(2):193-202. doi:10.11844/cjcb.2023.02.0002.
[17]	YAO Z X, TU J H, LIU Y L, et al. Long non-coding RNA LINC00342 promotes the proliferation,invasion,and migration of primary hepatocellular carcinoma cells by regulating the expression of miRNA-19a-3p,miRNA-545-5p,and miRNA-203a-3p[J]. Biochem Genet, 2023, 10(1):32-35. doi:10.1007/s10528-023-10420-x.
[18]	唐凤英, 董汾, 曾玉婷, 等. miR-203a-3p通过ALOX15途径抑制胃癌细胞铁死亡[J]. 中南医学科学杂志, 2022, 50(6):796-800.
	TANG F Y, DONG F, ZENG Y T, et al. miR-203a-3p inhibits iron death in gastric cancer cells via the ALOX15 pathway[J]. Medical Science Journal of Central South China, 2022, 50(6):796-800. doi:10.15972/j.cnki.43-1509/r.2022.06.004.
[19]	YANG P, ZHANG D, ZHOU F, et al. MiR-203a-3p-DNMT3B feedback loop facilitates non-small cell lung cancer progression[J]. Hum Cell, 2022, 35(4):1219-1233. doi:10.1007/s13577-022-00728-y.
[20]	LIU R, YANG X. LncRNA LINC00342 promotes gastric cancer progression by targeting the miR-545-5p/CNPY2 axis[J]. BMC Cancer, 2021, 21(1):1163-1174. doi:10.1186/s12885-021-08829-x.
[21]	QASEMI RAD M, POURESMAEIL V, HOSSEINI MOJAHED F, et al. Clinicopathological utility of miR-203a-3p in diagnosing colorectal cancer[J]. Mol Biol Rep, 2022, 49(7):6975-6985. doi:10.1007/s11033-022-07465-3.

基因名称	引物序列（5′→3′）	产物大小/bp
LINC00342	上游：CGTTCCAATGTGTTGGGTA	52
LINC00342	下游：TGGGAGGAGGTTGAGATGC	52
GAPDH	上游：GACCCACTCCTCCACCTTTG	138
GAPDH	下游：CCAAGCGCATGTTGCTGTAG	138
miR-203a-3p	上游：CGGCGTGAAATGTTTAGGA	67
miR-203a-3p	下游：ATCCGGAATCCGTAACGAT	67
U6	上游：CTCGCTTCGGCAGCACAGACTT	143
U6	下游：AACGCTTCACGAATTTGCGTAA	143

基因名称	引物序列（5′→3′）	产物大小/bp
LINC00342	上游：CGTTCCAATGTGTTGGGTA	52
LINC00342	下游：TGGGAGGAGGTTGAGATGC	52
GAPDH	上游：GACCCACTCCTCCACCTTTG	138
GAPDH	下游：CCAAGCGCATGTTGCTGTAG	138
miR-203a-3p	上游：CGGCGTGAAATGTTTAGGA	67
miR-203a-3p	下游：ATCCGGAATCCGTAACGAT	67
U6	上游：CTCGCTTCGGCAGCACAGACTT	143
U6	下游：AACGCTTCACGAATTTGCGTAA	143

组织类型	n	LINC00342	miR-203a-3p
癌旁组织	133	1.00±0.04	1.00±0.06
结直肠癌组织	133	2.41±0.42	0.65±0.11
t		38.542^＊＊	32.214^＊＊

组织类型	n	LINC00342	miR-203a-3p
癌旁组织	133	1.00±0.04	1.00±0.06
结直肠癌组织	133	2.41±0.42	0.65±0.11
t		38.542^＊＊	32.214^＊＊

临床病理参数	n	LINC00342			miR-203a-3p
临床病理参数	n	高表达组（n=81）	低表达组（n=52）	χ²	高表达组（n=56）	低表达组（n=77）	χ²
年龄
<55岁	61	40（65.57）	21（34.43）	1.033	29（47.54）	32（52.46）	1.366
≥55岁	72	41（56.94）	31（43.06）	1.033	27（37.50）	45（62.50）	1.366
性别
男	68	45（66.18）	23（33.82）	1.625	28（41.18）	40（58.82）	0.049
女	65	36（55.38）	29（44.62）	1.625	28（43.08）	37（56.92）	0.049
肿瘤部位
结肠	66	42（63.64）	24（36.36）	0.411	27（40.91）	39（59.09）	0.077
直肠	67	39（58.21）	28（41.79）	0.411	29（43.28）	38（56.72）	0.077
肿瘤分化程度
低分化	60	49（81.67）	11（18.33）	19.794^＊＊	9（15.00）	51（85.00）	32.947^＊＊
中高分化	73	32（43.84）	41（56.16）	19.794^＊＊	47（64.38）	26（35.62）	32.947^＊＊
肿瘤大小
<3 cm	63	40（63.49）	23（36.51）	0.337	23（36.51）	40（63.49）	1.538
≥3 cm	70	41（58.57）	29（41.43）	0.337	33（47.14）	37（52.86）	1.538
TNM分期
Ⅰ—Ⅱ期	69	28（40.58）	41（59.42）	24.871^＊＊	39（56.52）	30（43.48）	12.225^＊＊
Ⅲ期	64	53（82.81）	11（17.19）	24.871^＊＊	17（26.56）	47（73.44）	12.225^＊＊
淋巴结转移
有	64	53（82.81）	11（17.19）	24.871^＊＊	17（26.56）	47（73.44）	12.225^＊＊
无	69	28（40.58）	41（59.42）	24.871^＊＊	39（56.52）	30（43.48）	12.225^＊＊