外泌体来源的环状RNA在肿瘤诊疗中的价值

doi:10.3969/j.issn.1673-8640.2020.12.003

摘要/Abstract

摘要：

外泌体是细胞分泌的一种微小囊泡,内含多种生物分子,在细胞通信中发挥重要作用。环状RNA（circRNA）是外泌体中的一类核酸分子,是以共价键结合的闭合环状RNA,无5'端帽子和3'端poly（A）尾,主要充当微小RNA（miRNA）海绵,在基因表达中发挥重要的调控作用。外泌体来源的circRNA可调节肿瘤的增殖、转移和耐药,并且大量存在于肿瘤患者的血浆中,或可作为肿瘤早期诊断和预后评估的生物标志物。文章主要介绍外泌体 circRNA在不同肿瘤发生、发展中的生物学功能,为外泌体来源的circRNA在肿瘤诊疗领域中的应用提供依据。

关键词: 外泌体, 环状RNA, 肿瘤

Abstract:

Exosomes refer to small vesicles secreted by cells,containing various molecules and playing a role in intercellular communication. Circular RNA is a class of nucleic acid molecules contained in exosomes. It forms circular structures by covalent bonds without a 5' cap and a 3' poly（A） tail,mainly functioning as miRNA sponges and playing an important regulatory role in gene expression. Exosome-derived circRNA can promote tumor proliferation,metastasis and drug resistance,which are enriched in plasma and may be served as biomarkers for diagnosis and prognosis in early tumor. This review highlights the biological functions of exosomal circRNA in the onset and development of different tumors and provides a reference for the application of exosome-derived circRNA in tumor diagnosis and treatment.

Key words: Exosome, Circular RNA, Tumor

中图分类号:

R446.1

杨文静, 吕丽华, 姚嘉怡, 王皓, 张春燕, 王蓓丽, 潘柏申, 郭玮. 外泌体来源的环状RNA在肿瘤诊疗中的价值[J]. 检验医学, 2020, 35(12): 1213-1219.

YANG Wenjing, LÜ Lihua, YAO Jiayi, WANG Hao, ZHANG Chunyan, WANG Beili, PAN Baishen, GUO Wei. Role of exosome-derived circular RNA in tumor diagnosis and treatment[J]. Laboratory Medicine, 2020, 35(12): 1213-1219.

图/表 2

参考文献 46

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生物功能	circRNA名称	肿瘤类型	变化趋势	分子机制	临床参数分析	参考文献
调控细胞增殖	circRASSF2	喉鳞状细胞癌	↑	miRNA-302b-3p/IGF-1R	T分期、淋巴结转移	[10]
	circDB	HCC	↑	miRNA-34a/USP7/Cyclin A2		[11]
	circIFT80	结直肠癌	↑	miRNA-1236-3p/HOXB7	肿瘤分期、肿瘤大小、远处转移	[12]
	circFMN2	结直肠癌	↑	miRNA-1182	肿瘤大小、肿瘤分期、远处转移、TNM分期	[13]
	circNRIP1	胃癌	↑	miRNA-149-5p/AKT1/mTOR	肿瘤大小、淋巴浸润	[14]
	circ_0044516	前列腺癌	↑	miRNA-29a-3p	肿瘤转移	[15]
调控侵袭以及转移	circPTGR1	HCC	↑	miRNA449a/MET	临床分期、预后	[16]
	circ_100338	HCC	↑	HUVEC	生存时间、TNM分期、血管侵犯、肺转移	[17]
	circCdr1as	HCC	↑	miRNA-1270/AFP		[18]
	circRanGAP1	胃癌	↑	miRNA-877-3p/VEGFA	TNM分期、淋巴结转移、低生存率	[19]
	ciRS-133	胃癌	↑	miRNA-133/PRDM16	白色脂肪组织褐变	[20]
	circPED8A	胰腺癌	↑	miRNA-338/MACC1/MET	十二指肠浸润、血管浸润、T因子、TNM分期、低生存率	[21]
	circIARS	胰腺癌	↑	miRNA-12/RhoA	肝转移、脉管侵犯、TNM分期	[22]
	circPRMT5	膀胱尿路上皮癌	↑	miRNA-30c/SNAIL1/ E-钙黏蛋白	淋巴结转移、晚期进展	[23]
	circPUM1	卵巢癌	↑	miRNA-615-5p,miRNA-6753-5p		[24]
	circWHSC1	卵巢癌	↑	miRNA-1182,miRNA-145		[25]
	circ_0000677	结直肠癌	↑	Wnt/β-catenin		[26]
	circ_0000284	胆管癌	↑	miRNA-637/LY6E	分化程度、TNM分期、淋巴结浸润	[27]
调控药物耐药	FECR1	小细胞肺癌	↑	miRNA584-ROCK1	低生存率、化疗反应	[28]
	circCdr1as	卵巢癌	↓	miRNA-1270	顺铂耐药	[29]
	circ_0000338	结直肠癌	↑	/	奥沙利铂耐药	[30]
	ciRS-122	结直肠癌	↑	miRNA-122/M2-PK	奥沙利铂耐药	[31]

生物功能	circRNA名称	肿瘤类型	变化趋势	分子机制	临床参数分析	参考文献
调控细胞增殖	circRASSF2	喉鳞状细胞癌	↑	miRNA-302b-3p/IGF-1R	T分期、淋巴结转移	[10]
	circDB	HCC	↑	miRNA-34a/USP7/Cyclin A2		[11]
	circIFT80	结直肠癌	↑	miRNA-1236-3p/HOXB7	肿瘤分期、肿瘤大小、远处转移	[12]
	circFMN2	结直肠癌	↑	miRNA-1182	肿瘤大小、肿瘤分期、远处转移、TNM分期	[13]
	circNRIP1	胃癌	↑	miRNA-149-5p/AKT1/mTOR	肿瘤大小、淋巴浸润	[14]
	circ_0044516	前列腺癌	↑	miRNA-29a-3p	肿瘤转移	[15]
调控侵袭以及转移	circPTGR1	HCC	↑	miRNA449a/MET	临床分期、预后	[16]
	circ_100338	HCC	↑	HUVEC	生存时间、TNM分期、血管侵犯、肺转移	[17]
	circCdr1as	HCC	↑	miRNA-1270/AFP		[18]
	circRanGAP1	胃癌	↑	miRNA-877-3p/VEGFA	TNM分期、淋巴结转移、低生存率	[19]
	ciRS-133	胃癌	↑	miRNA-133/PRDM16	白色脂肪组织褐变	[20]
	circPED8A	胰腺癌	↑	miRNA-338/MACC1/MET	十二指肠浸润、血管浸润、T因子、TNM分期、低生存率	[21]
	circIARS	胰腺癌	↑	miRNA-12/RhoA	肝转移、脉管侵犯、TNM分期	[22]
	circPRMT5	膀胱尿路上皮癌	↑	miRNA-30c/SNAIL1/ E-钙黏蛋白	淋巴结转移、晚期进展	[23]
	circPUM1	卵巢癌	↑	miRNA-615-5p,miRNA-6753-5p		[24]
	circWHSC1	卵巢癌	↑	miRNA-1182,miRNA-145		[25]
	circ_0000677	结直肠癌	↑	Wnt/β-catenin		[26]
	circ_0000284	胆管癌	↑	miRNA-637/LY6E	分化程度、TNM分期、淋巴结浸润	[27]
调控药物耐药	FECR1	小细胞肺癌	↑	miRNA584-ROCK1	低生存率、化疗反应	[28]
	circCdr1as	卵巢癌	↓	miRNA-1270	顺铂耐药	[29]
	circ_0000338	结直肠癌	↑	/	奥沙利铂耐药	[30]
	ciRS-122	结直肠癌	↑	miRNA-122/M2-PK	奥沙利铂耐药	[31]

名称	肿瘤类型	研究对象		标本类型	趋势	临床参数分析	AUC	敏感性/%	特异性/%	参考文献
名称	肿瘤类型	病例数	对照例数	标本类型	趋势	临床参数分析	AUC	敏感性/%	特异性/%	参考文献
circ_0004771	结直肠癌	110	35（HC）	血清	↑	TNM分期、远处转移	0.88	80.91	82.86	[36]
circHIPK3	结直肠癌	20	20（HC）	血清	↑		0.771	71	80	[37]
circ_0065149	EGC	39	41（HC）	血浆	↓	肿瘤大小、外周神经侵袭	0.64	48.7	90.2	[38]
circ_0051443	HCC	60	60（HC）	血浆	↓	肝硬化	0.808 9			[39]
FECR1	小细胞肺癌	61	55（HC）	血清	↑	低生存率、化疗反应				[31]
circ_002178	肺腺癌	120	30（HC）	血清	↑		0.996 7			[40]
circ_0001492、 circ_0001346	肺腺癌	15	15（HC）	血浆	↑					[41]
circ_00005795、 circ_0088088	乳腺癌	8	8（HC）	血清	↓ ↑					[42-43]
circ_0000284	胆管癌	25	25（HC）	血浆	↑	肿瘤分化程度、TNM分期、淋巴结浸润				[27]
名称	肿瘤类型	研究对象		标本类型	趋势	临床参数分析	AUC	敏感性/%	特异性/%	参考文献
名称	肿瘤类型	病例数	对照例数	标本类型	趋势	临床参数分析	AUC	敏感性/%	特异性/%	参考文献
circPED8A	胰腺癌	93	20（HC）	血浆	↑	十二指肠浸润、血管浸润、T因子、TNM分期、低生存率				[21]
circIARS	胰腺癌	20（伴转移）	20（不伴转移）	血浆	↑	肝转移、脉管侵犯、TNM 分期				[22]
circ_0044516	前列腺癌	6	6（HC）	血液	↑					[15]
circPRMT5	膀胱尿路上皮癌	血清：71 尿液：18	血清：35 （HC）尿液：18 （HC）	血清尿液	↑	淋巴结转移、晚期肿瘤进展				[23]
circ_0109046、 circ_0002577	子宫内膜癌	10	10（HC）	血清	↑ ↑					[44]
circ_007293、 circ_031752、 circ_020135	甲状腺乳头状癌	3	3（良性甲状腺肿）	血清	↑ ↑ ↓					[45]
circ_0001946、 circ_0043603	食管鳞状细胞癌	50	50 （HC）	血浆	↓	预后	0.928	84	89	[46]

名称	肿瘤类型	研究对象		标本类型	趋势	临床参数分析	AUC	敏感性/%	特异性/%	参考文献
名称	肿瘤类型	病例数	对照例数	标本类型	趋势	临床参数分析	AUC	敏感性/%	特异性/%	参考文献
circ_0004771	结直肠癌	110	35（HC）	血清	↑	TNM分期、远处转移	0.88	80.91	82.86	[36]
circHIPK3	结直肠癌	20	20（HC）	血清	↑		0.771	71	80	[37]
circ_0065149	EGC	39	41（HC）	血浆	↓	肿瘤大小、外周神经侵袭	0.64	48.7	90.2	[38]
circ_0051443	HCC	60	60（HC）	血浆	↓	肝硬化	0.808 9			[39]
FECR1	小细胞肺癌	61	55（HC）	血清	↑	低生存率、化疗反应				[31]
circ_002178	肺腺癌	120	30（HC）	血清	↑		0.996 7			[40]
circ_0001492、 circ_0001346	肺腺癌	15	15（HC）	血浆	↑					[41]
circ_00005795、 circ_0088088	乳腺癌	8	8（HC）	血清	↓ ↑					[42-43]
circ_0000284	胆管癌	25	25（HC）	血浆	↑	肿瘤分化程度、TNM分期、淋巴结浸润				[27]
名称	肿瘤类型	研究对象		标本类型	趋势	临床参数分析	AUC	敏感性/%	特异性/%	参考文献
名称	肿瘤类型	病例数	对照例数	标本类型	趋势	临床参数分析	AUC	敏感性/%	特异性/%	参考文献
circPED8A	胰腺癌	93	20（HC）	血浆	↑	十二指肠浸润、血管浸润、T因子、TNM分期、低生存率				[21]
circIARS	胰腺癌	20（伴转移）	20（不伴转移）	血浆	↑	肝转移、脉管侵犯、TNM 分期				[22]
circ_0044516	前列腺癌	6	6（HC）	血液	↑					[15]
circPRMT5	膀胱尿路上皮癌	血清：71 尿液：18	血清：35 （HC）尿液：18 （HC）	血清尿液	↑	淋巴结转移、晚期肿瘤进展				[23]
circ_0109046、 circ_0002577	子宫内膜癌	10	10（HC）	血清	↑ ↑					[44]
circ_007293、 circ_031752、 circ_020135	甲状腺乳头状癌	3	3（良性甲状腺肿）	血清	↑ ↑ ↓					[45]
circ_0001946、 circ_0043603	食管鳞状细胞癌	50	50 （HC）	血浆	↓	预后	0.928	84	89	[46]