检验医学 ›› 2020, Vol. 35 ›› Issue (12): 1213-1219.DOI: 10.3969/j.issn.1673-8640.2020.12.003
杨文静1, 吕丽华1, 姚嘉怡1, 王皓1, 张春燕2, 王蓓丽1, 潘柏申1, 郭玮1()
收稿日期:
2020-03-05
出版日期:
2020-12-30
发布日期:
2020-12-31
作者简介:
null基金资助:
YANG Wenjing1, LÜ Lihua1, YAO Jiayi1, WANG Hao1, ZHANG Chunyan2, WANG Beili1, PAN Baishen1, GUO Wei1()
Received:
2020-03-05
Online:
2020-12-30
Published:
2020-12-31
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。
中图分类号:
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.
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] |
表1 外泌体来源的circRNA在肿瘤中的生物学功能
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 | |
---|---|---|---|---|---|---|---|---|---|---|
病例数 | 对照例数 | |||||||||
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 | |
病例数 | 对照例数 | |||||||||
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] |
表2 外泌体来源的circRNA在不同肿瘤中的应用
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 | |
---|---|---|---|---|---|---|---|---|---|---|
病例数 | 对照例数 | |||||||||
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 | |
病例数 | 对照例数 | |||||||||
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] |
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