Genome-wide identification and characterization of circular RNA in resected hepatocellular carcinoma and background liver tissue

Abstract

Circular RNA (circRNA) is a type of non-coding RNA known to affect cancer-related micro RNAs and various transcription factors. circRNA has promise as a cancer-related biomarker because its circular structure affords high stability. We found using high-throughput sequencing that seven candidate circRNAs (hsa_circ_0041150, hsa_circ_0025624, hsa_circ_0001020, hsa_circ_0028129, hsa_circ_0008558, hsa_circ_0036683, hsa_circ_0058087) were downregulated in HCC. The expression of these circRNAs was examined by quantitative PCR in 233 sets of HCC and matched background normal liver tissues, and correlations between candidate circRNA expression and prognosis were evaluated. The results of quantitative PCR showed that expression of hsa_circ_0041150, hsa_circ_0001020 and hsa_circ_0008558 was significantly lower in HCC than in background normal liver tissues. Kaplan–Meier analysis revealed that low expression of hsa_circ_0001020, hsa_circ_0036683, and hsa_circ_0058087 was associated with poor recurrence-free (RFS) and overall survival (OS) in HCC. Additionally, multivariate analysis revealed that low hsa_circ_0036683 expression was a significant prognostic factor, independent from other clinicopathological features, for inferior RFS and OS. There was no significant association between the expression of these circRNAs and hepatitis B/C status or cirrhosis. This study therefore identified circRNAs as potential prognostic markers for patients who undergo curative surgery for HCC and highlighted hsa_circ_0036683 as the most useful biomarker.

Circular RNAs modulate Hippo-YAP signaling: functional mechanisms in cancer

“…Differential expression of various circRNAs has been investigated in various forms of liver related pathologies 107 , including liver cancer 108 , 109 . In regards to circRNA regulation, some circRNAs have been noted to be dysregulated in hepatocellular carcinoma (HCC) 110 , 111 .…”

Circular RNAs as Diagnostic and Prognostic Biomarkers of Hepatocellular Carcinoma: A Meta-analysis

“…肝细胞癌(HCC)是最常见的原发性肝癌(占病 例的 75-85%) ，也是世界上继肺癌、结直肠癌和胃癌 之后的第四大癌症相关死亡原因 [1]。 HCC 是一种高致 死率的肿瘤，大多数病例在晚期才被发现，发病率与 死亡率之比接近 1。例如，2015 年约有 85.4 万例肝癌 新发病例， 而全世界每年约有 81 万例肝癌相关死亡 [2]。 HCC 高危人群管理中的一个主要问题是早期诊断检 测的敏感性 [1]。 研究表明， 早期诊断的患者可早期治疗， 预后良好，5 年生存率>70% [3]。目前，活检的组织学评 估仍然是癌症组织检测的金标准 [4,5]，虽然肝活检具有 较高的敏感性和特异性，是最可靠的诊断方法，但由于 其侵袭性和不良反应，在临床中的应用仍受到限制。此 外，未能识别转移和复发高危患者也导致 HCC 患者预后 不理想。因此众多学者一直致力于研究特定生物标志物 作为 HCC 早期诊断和预后工具。环状 RNA(CircRNA) 是一种新型的内源性非编码 RNA，由蛋白质编码 mRNA 或线性非编码 RNA"反向剪接"产生，它们连接上游 3'剪 接位点和下游 5'剪接位点， 形成共价封闭的环状结构 [6][7][8]。 它们高度稳定、丰富、保守，参与多种生理病理过程， 可能是癌症发生的关键因素。目前，Fathial 等人 [9]发现 has_circ_0064286 可作为 HCC 诊断的潜在生物标志物 (AUC=0.97)。此外，上调的 hsa_circ_0001020 与侵袭 性特征显著相关，可能是 HCC 患者总生存期(OS)的 一个危险因素 [10]。此前，一些已发表的荟萃分析报道了 circRNA 对 HCC 的诊断和预后价值 [11][12][13][14]。然而纳入的 研究和患者相对较少，并且缺乏该领域的最新研究数据。 因此，我们进行了这项荟萃分析，以总结 CircRNA 的失 调与 HCC 的诊断和预后之间的关系。…”

Circular RNAs in hepatocellular carcinoma: Recent advances

“…For example, high expression of hsa_circ_0001649 or circ_0004913 signifies longer OS in HCC patients[ 149 , 150 ]. Furthermore, high circSETD3 or hsa_circ_0036683 expression indicates better OS and RFS in HCC patients[ 57 , 151 ]. Moreover, high hsa_circ_0005986 expression implies better OS and PFS in HCC patients[ 152 ].…”