Kishikawa Takahiro, Otsuka Motoyuki, Ohno Motoko, Yoshikawa Takeshi, Takata Akemi, Koike Kazuhiko
Takahiro Kishikawa, Motoyuki Otsuka, Motoko Ohno, Takeshi Yoshikawa, Akemi Takata, Kazuhiko Koike, Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
World J Gastroenterol. 2015 Jul 28;21(28):8527-40. doi: 10.3748/wjg.v21.i28.8527.
Pancreatic cancer remains difficult to treat and has a high mortality rate. It is difficult to diagnose early, mainly due to the lack of screening imaging modalities and specific biomarkers. Consequently, it is important to develop biomarkers that enable the detection of early stage tumors. Emerging evidence is accumulating that tumor cells release substantial amounts of RNA into the bloodstream that strongly resist RNases in the blood and are present at sufficient levels for quantitative analyses. These circulating RNAs are upregulated in the serum and plasma of cancer patients, including those with pancreatic cancer, compared with healthy controls. The majority of RNA biomarker studies have assessed circulating microRNAs (miRs), which are often tissue-specific. There are few reports of the tumor-specific upregulation of other types of small non-coding RNAs (ncRNAs), such as small nucleolar RNAs and Piwi-interacting RNAs. Long ncRNAs (lncRNAs), such as HOTAIR and MALAT1, in the serum/plasma of pancreatic cancer patients have also been reported as diagnostic and prognostic markers. Among tissue-derived RNAs, some miRs show increased expression even in pre-cancerous tissues, and their expression profiles may allow for the discrimination between a chronic inflammatory state and carcinoma. Additionally, some miRs and lncRNAs have been reported with significant alterations in expression according to disease progression, and they may thus represent potential candidate diagnostic or prognostic biomarkers that may be used to evaluate patients once detection methods in peripheral blood are well established. Furthermore, recent innovations in high-throughput sequencing techniques have enabled the discovery of unannotated tumor-associated ncRNAs and tumor-specific alternative splicing as novel and specific biomarkers of cancers. Although much work is required to clarify the release mechanism, origin of tumor-specific circulating RNAs, and selectivity of carrier complexes, and technical advances must also be achieved, such as creating a consensus normalization protocol for quantitative data analysis, circulating RNAs are largely unexplored and might represent novel clinical biomarkers.
胰腺癌仍然难以治疗，死亡率很高。早期诊断困难，主要是由于缺乏筛查成像手段和特异性生物标志物。因此，开发能够检测早期肿瘤的生物标志物很重要。越来越多的新证据表明，肿瘤细胞会向血液中释放大量RNA，这些RNA能强烈抵抗血液中的核糖核酸酶，且其含量足以进行定量分析。与健康对照相比，这些循环RNA在癌症患者（包括胰腺癌患者）的血清和血浆中上调。大多数RNA生物标志物研究评估的是循环微小RNA（miR），它们通常具有组织特异性。关于其他类型的小非编码RNA（ncRNA），如小核仁RNA和Piwi相互作用RNA的肿瘤特异性上调的报道较少。胰腺癌患者血清/血浆中的长链非编码RNA（lncRNA），如HOTAIR和MALAT1，也已被报道为诊断和预后标志物。在组织来源的RNA中，一些miR即使在癌前组织中也显示出表达增加，其表达谱可能有助于区分慢性炎症状态和癌症。此外，一些miR和lncRNA已被报道根据疾病进展表达有显著变化，因此它们可能代表潜在的候选诊断或预后生物标志物，一旦外周血检测方法完善，就可用于评估患者。此外，高通量测序技术的最新创新使得发现未注释的肿瘤相关ncRNA和肿瘤特异性可变剪接成为癌症的新型特异性生物标志物。尽管需要做大量工作来阐明肿瘤特异性循环RNA的释放机制、来源以及载体复合物的选择性，并且还必须取得技术进步，如创建定量数据分析的共识标准化方案，但循环RNA在很大程度上尚未被探索，可能代表新型临床生物标志物。
