Circular RNA profiling and its potential for esophageal squamous cell cancer diagnosis and prognosis
Circular RNA profiling and its potential for esophageal squamous cell cancer diagnosis and prognosis
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DOI：
10.1186/s12943-018-0936-4
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发表时间：
2019-01-23
期刊：
影响因子：
37.3
通讯作者：
Li, Baosheng
中科院分区：
文献类型：
--
作者：
Fan, Liyuan;Cao, Qiang;Li, Baosheng
食管鳞状细胞癌是世界范围内发病率和死亡率较高的疾病。然而，其诊断和预后生物标志物的特异性和敏感性仍然不令人满意。近年来，作为生物标志物的环状RNA（circular RNA，circRNA）已被广泛研究，但关于circRNA在食管鳞癌中的表达及其临床意义的研究却很少。我们在3对ESCC冷冻肿瘤组织和非肿瘤组织中进行了环状RNA微阵列检测，发现1045个上调和1032个下调的circRNA，其中6个circRNA（hsa_circ_0062459、hsa_circ_0076535、hsa_circ_0072215、hsa_circ_0042261、hsa_circ_0001946和hsa_circ_0043603）显示与通过qRT-PCR的微阵列结果一致。在血浆中也检测到3种circRNA（hsa_circ_0062459、hsa_circ_0001946和hsa_circ_0043603），其中除hsa_circ_0062459外的2种可用作诊断生物标志物，并在细胞条件培养条件培养基的外泌体中发现。hsa_circ_0001946的AUC、灵敏度和特异性分别为0.894、92和80%，hsa_circ_0043603的AUC、灵敏度和特异性分别为0.836、64和92%，而组合它们的特征分别为0.928、84和98%。Hsa_circ_0001946被证实预测冷冻和FFPE组织中的复发、总生存期（OS）和无病生存期（DFS），而其过表达降低细胞增殖、迁移和侵袭。
Esophageal squamous cell cancer (ESCC) is a high incidence and mortality disease worldwide. However, specificity and sensitivity of its diagnostic and prognostic biomarkers are still unsatisfactory. Recently, circular RNAs (circRNAs) as biomarkers have been studied extensively while the expression profile and clinical significance of circRNAs in ESCC have rarely been studied. We performed circular RNA microarray in 3 pairs of ESCC frozen tumor and non-tumor tissues to identify ESCC-related circRNAs and found 1045 up-regulated and 1032 down-regulated circRNAs among which 6 circRNAs (hsa_circ_0062459, hsa_circ_0076535, hsa_circ_0072215, hsa_circ_0042261, hsa_circ_0001946, and hsa_circ_0043603) displayed consistency with microarray results by qRT-PCR. 3 circRNAs (hsa_circ_0062459, hsa_circ_0001946, and hsa_circ_0043603) were also detected in plasma and 2 of them except hsa_circ_0062459 could be used as diagnostic biomarkers and found in exosome of cell-conditioned culture conditioned media. The AUC, sensitivity and specificity of hsa_circ_0001946 were 0.894, 92, 80%, of hsa_circ_0043603 were 0.836, 64, 92% while a signature combining them were 0.928, 84 and 98%. Hsa_circ_0001946 was confirmed to predict the recurrence, overall survival (OS) and disease-free survival (DFS) in frozen and FFPE tissues, while its overexpression decreased cell proliferation, migration, and invasion.