肿瘤易感候选基因2在肿瘤中的作用及机制研究

摘 要：长链非编码RNA是非编码RNA家族的重要组成成员,随着对其研究的不断深入,发现在恶性肿瘤中呈异常表达的长链非编码RNA对肿瘤的发生发展起到了重要的调控作用。肿瘤易感候选基因2（CASC2）是一种新被发现的长链非编码RNA,其在诸多机体恶性肿瘤中呈下调表达并能够抑制肿瘤的多种恶性生物学行为,并有可能成为肿瘤诊治的生物学标志物;对CASC2调控作用机制的研究将为肿瘤诊断、预后评估及靶向治疗提供新的理论依据和干预靶点。本文就现有肿瘤内CASC2的调控作用及机制研究作一简要综述。     

甲状腺肿瘤与循环RNA研究进展

甲状腺癌是内分泌系统最常见的肿瘤。研究发现,外周血循环RNA含量在多种恶性肿瘤患者血清中特异性表达,是潜在的肿瘤诊断的生物学标志和药物治疗靶点。血清甲状腺特异mRNA(包括促甲状腺受体mRNA和甲状腺球蛋白mRNA)被报道在甲状腺肿瘤患者中异常表达,可以作为肿瘤诊断及其复发转移的分子标志物。近年研究显示,非编码RNA(non-coding RNA,ncRNA)在细菌、真菌和哺乳动物等多种生物体的活动中可作为癌基因或抑癌基因,对肿瘤的发生、发展发挥调控作用,并且在循环血中稳定存在,ncRNA有希望成为肿瘤诊断的新型无创标志物。该研究介绍与甲状腺肿瘤相关的循环RNA最新研究进展,并着重讨论循环mRNA、微小RNA(miRNA)、长链非编码RNA(long non-coding,lncRNA)及环状RNA(circRNA)在甲状腺肿瘤发生、转移中的作用。     

circRNA与消化道肿瘤：进展和机遇

消化道肿瘤是我国常见的恶性肿瘤,发病率逐年上升,有效筛查和早期诊断是临床上亟需解决的问题。环状RNA（circRNA）是一类新的非编码RNA,可通过多种机制在生物学功能中发挥重要作用,如“miRNA海绵”、转录调节剂以及与RNA结合蛋白的结合。最近也有研究发现部分细胞质circRNA可以翻译成蛋白质。circRNA逐渐成为RNA和消化道肿瘤研究领域的热点之一,但是大多数消化道肿瘤相关circRNA的功能及其作用机制仍未知。本文就消化道肿瘤相关circRNA最新的研究进展及热点进行述评。     

微小RNAs在乳腺癌中的应用价值

乳腺癌是目前女性最常见的恶性肿瘤,2012年全球共有170万乳腺癌新增病例,且乳腺癌的发病率和死亡率持续上升.肿瘤标志物在乳腺癌的早期诊断、个体化治疗、预后及疗效预测等方面发挥重要作用.目前常见的肿瘤标志物包括蛋白酶类、肿瘤特异性抗原、代谢产物等.然而,这些标志物特异性并不高,特别是在肿瘤早期筛查、良恶性肿瘤的区分和低度恶性肿瘤的诊断方面特异性较低.微小RNA（microRNA,miRNA）是一类调控基因表达的非编码小分子RNA,参与多种生物学信号通路的调节,组织或循环中miRNA的异常表达与乳腺癌密切相关.循环miRNA作为非侵袭性、实时监测的新型肿瘤标志物,在乳腺癌领域得到了广泛研究,可以作为分析肿瘤转移、预后判断、疗效评价和个体化治疗的有利依据.本文介绍miRNA与乳腺癌的相关性,并针对循环miRNA在乳腺癌的诊断、预后以及疗效评价方面的应用价值作一综述.     

piRNA在卵巢癌中的研究进展

PIWI 蛋白相互作用RNA（PIWI-interacting RNA，piRNA）及PIWI 蛋白通过表观遗传沉默影响肿瘤的发生发展，并与恶性肿瘤的增殖、侵袭、转移和预后不良密切相关，是潜在的新型肿瘤标志物和预后判断因子。卵巢癌是妇科三大恶性肿瘤之一，晚期易复发转移、产生耐药和病死率高，目前仍缺乏有效的早期肿瘤标志物和诊断方法。近年有研究表明，piRNA和PIWI蛋白在卵巢癌中呈异常表达，通过转录后机制参与调控卵巢癌的发生发展。本文主要从piRNA的生物学特性、在肿瘤中表观遗传沉默的相关机制和piRNA 在卵巢癌中的作用及其机制最新研究进展进行综述，为研究早期诊断卵巢癌的分子标志物提供参考依据。     

环状RNA作为生物标志物在结直肠癌发生发展及预后中的作用

[摘要] 结直肠癌（colorectal cancer,CRC）是常见的消化系统恶性肿瘤之一,其发病率和病死率处于各类肿瘤的第3 位。环状RNA（circular RNA,circRNA）是一种新型长链非编码RNA（long non-coding RNA,lncRNA）,早期被当作剪切过程中的副产物且无生物学意义和功能。近年来研究发现,环状RNA不具有5’末端和3’末端的闭合环状,其结构较其他非编码RNA稳定,能作为RNA的海绵体以及调控剪切和转录,也能影响蛋白质以及核糖体,参与肿瘤的发生、发展和预后,在肿瘤的早期诊断、分型和分期中也具有一定的潜能。随着研究的深入,环状RNA在肿瘤组织的差异表达与CRC的发生、发展以及预后存在密切的关系,为CRC的诊断、治疗及预后提供了可观的发展前景。本文对环状RNA作为CRC生物标志物近年来的研究进展作一综述。     

circRNA的生物学功能及其在卵巢癌中的研究进展

生物信息技术的快速发展正在推动一些隐藏的基因被人们所发现。环状RNA(circRNA)是内源性非编码RNA(ncRNA)家族的新成员,通过单链RNA分子的3’端和5’端连接而成,具有一定的广泛性、保守性、稳定性和组织特异性。近年来,随着高通量测序技术和生物信息学的不断发展,大量内源性circRNA在各种细胞类型中均可被检测到,且circRNA具有发挥微小RNA(miRNA)海绵作用、调控基因表达及翻译等生物学功能,同时在生物发育过程中和疾病诊断中起着至关重要的作用。circRNA具有差异性表达的特点,与多种恶性肿瘤的发生、发展密切相关,在肿瘤中发挥抑癌基因或癌基因的作用,有望成为恶性肿瘤的新型诊断标志物、分子治疗靶点和预后评估指标。目前,仅有少量关于circRNA在卵巢癌中研究进展的报道,本文拟从circRNA的生物学功能及其在卵巢癌中的研究进展进行简要综述。     

环状RNA在胃癌诊断和治疗中作用的研究进展

胃癌是世界范围内第五大常见恶性肿瘤,居肿瘤相关死亡原因的第三位。晚期诊断、高复发和高转移与其不良预后相关。胃癌的发病机制非常复杂,其潜在机制尚待探索。环状RNA(circular RNA,circRNA)是一类以单链共价闭环结构为特征的新型长链非编码RNA,主要在转录和转录后水平上参与基因表达调控。近年来研究发现,circRNA参与许多生物学过程,包括肿瘤的发生和发展。circRNA在胃癌中起着关键作用,其在胃癌中异常表达与胃癌组织的病理特征相关,并通过调控一些靶基因、miRNA和蛋白质的表达,参与调控胃癌细胞的增殖、迁移、侵袭和凋亡等生物学过程,提示circRNA可能是胃癌诊断和预后潜在的生物标志物和治疗靶点。本文论述近年来circRNA的生物学功能及其在胃癌诊治中作用的相关研究进展。     

LncRNA 与恶性肿瘤侵袭转移研究进展

转移是恶性肿瘤的重要特征,其涉及多个复杂生物学过程。LncRNA是指长度>200个核苷酸但无蛋白质编码功能的一种长链非编码RNA,可通过其异常表达来调控肿瘤细胞的增殖、分化、凋亡,尤其在恶性肿瘤转移过程中发挥重要作用,这为肿瘤疾病的诊断及治疗提供新的思路。     

长链非编码 RNA 在泌尿系统恶性肿瘤中的研究进展

目前泌尿系统恶性肿瘤在我国的发病率越来越高,对于肿瘤的防治已经成为现代医学研究的重点。长链非编码 RNA（long non －coding RNA,lncRNA）是一组长度超过200nt（nucleotide）,缺少完整蛋白编码功能的 RNA,曾被认为是基金组转录的“噪音”。目前研究发现,lncRNA 具有多种生物学功能,在表观遗传学调控以及转录和转录后调控等发面发挥着重要作用,参与了泌尿系统疾病的发生发展。本文就 lncRNA 在泌尿系统恶性肿瘤中的研究进展作一综述,旨在为泌尿系统恶性肿瘤的诊断和治疗提供新的思路。     

循环 miRNA 在非小细胞肺癌诊断治疗及预后判断中的价值

微小 RNA（microRNAs,miRNAs）是一类参与基因转录后水平调控的小分子非编码 RNA,广泛参与肿瘤发生发展等过程的调节。循环 miRNAs 是在外周血中发现的 miRNAs,新近研究资料显示,循环 miR-NAs 作为一种新型生物标志物可能在肺癌的诊断、疗效评估和预后判断中有着重要的作用和价值。     

Circulating tumor markers: harmonizing the yin and yang of CTCs and ctDNA for precision medicine

Current trajectory of clinical care is heading in the direction of personalized medicine. In an ideal scenario, clinicians can obtain extensive diagnostic and prognostic information via minimally-invasive assays. Information available in the peripheral blood has the potential to bring us closer to this goal. In this review we highlight the contributions of circulating tumor cells and circulating tumor DNA and RNA (ctDNA/ctRNA) towards cancer therapeutic field. We discuss clinical relevance, summarize available and upcoming technologies, and hypothesize how future care could be impacted by a combined study.     

Detection of cadherin-6 mRNA by nested RT-PCR as a potential marker for circulating cancer cells in renal cell carcinoma

To detect circulating RCC cells, we established a nested RT-PCR system for cadherin-6 mRNA, which is specifically expressed in RCC. A total of 121 samples of peripheral blood (34 healthy volunteers and 87 patients with RCC) were analyzed in this study. Total RNA of the monocyte fraction of the blood was extracted, then nested RT-PCR using specific primers was performed to detect mRNA of N-cadherin or cadherin-6. Nested RT-PCR revealed that expression of cadherin-6 mRNA was not present in the blood of most healthy volunteers (absent in 32/34), but positive expression was observed in the blood at concentrations of 10 cells/ml or greater of the SKRC-33 RCC cell line, which is a strong expresser of cadherin-6. In peripheral blood from patients with metastatic disease, cadherin-6 mRNA was detected in 70.4% (19/27). Messenger RNA of cadherin-6 was detectable in 45.0% (27/60) of patients with localized tumors. The PCR-based detection system for peripheral blood samples from patients with metastatic disease could reveal the presence of circulating RCC cells in the blood. Detection of cadherin-6 mRNA in non-metastatic presurgical RCC patients suggests that careful follow-up study is necessary in these patients.     

肝细胞癌患者外周血循环DNA检测研究进展

 外周血循环DNA是指存在于血浆或血清中的胞外游离DNA。研究表明恶性肿瘤患者外周血循环DNA明显高于健康者,其表达水平及基因的改变与肿瘤的发生、发展及预后密切相关。检测外周血循环DNA对恶性肿瘤的早期诊断、疗效监测以及预后评估具有重要价值。就近年来肝细胞癌（HCC）患者外周血循环DNA检测研究进展作一综述。     

循环核小体与肿瘤研究进展

肿瘤患者外周血中循环核小体水平常常升高 ,在肿瘤化疗或放疗中核小体水平的变化过程与临床疗效有关 ,这将为肿瘤患者的治疗监测与疗效判断提供重要依据 ,就此方面的研究进展予以综述     

Prognosis of non-small cell lung cancer patients by detecting circulating cancer cells in the peripheral blood with multiple marker genes.

PURPOSE: Current lung cancer staging and prognosis methods are based on imaging methods, which may not be sensitive enough for early and accurate detection of metastasis. This study aims to validate the use of a panel of markers for circulating cancer cell detection to improve the accuracy of cancer staging, prognosis, and as a rapid assessment of therapeutic response. EXPERIMENTAL DESIGN: We analyzed the National Cancer Institute-Cancer Genome Anatomy Project database to identify potential marker genes for the detection of circulating cancer cells in peripheral blood. Nested real-time quantitative PCR and a scoring method using cancer cell load Lc were employed to correlate the amount of circulating cancer cells with clinical outcomes in 54 non-small cell lung cancer (NSCLC) patients. The Kaplan-Meier method was employed for analysis of prognostic variables. RESULTS: A panel of four marker genes was identified and experimentally validated. With these marker genes, we achieved an overall positive detection rate of 72% for circulating cancer cells in the peripheral blood of NSCLC patients. Patients who had higher Lc values had worse outcomes and shorter survival times. Patients with poor therapeutic response were revealed by positive detection of circulating cancer cells after therapy. The results correlated well with the patients' survival time. CONCLUSION: Circulating cancer cell detection by a panel of markers and the Lc scoring method can supplement the current tumor, node, metastasis staging method for improved prognosis and for rapid assessment of therapeutic response. Together, they may facilitate the design of better therapeutic strategies for the treatment of NSCLC patients.     

Recent translational research: circulating tumor cells in breast cancer patients

In breast cancer patients, hematogenous tumor cell dissemination can be detected, even at the single cell level, by applying immunocytochemical and molecular assays. Various methods for the detection of circulating tumor cells in the peripheral blood have been described. Results from recently reported studies suggest that circulating tumor cell levels may serve as a prognostic marker and for the early assessment of therapeutic response in patients with metastatic breast cancer. However, in early-stage breast cancer, the impact of circulating tumor cells is less well established than the presence of disseminated tumor cells in bone marrow; several clinical studies have demonstrated that cells of the latter type are an independent prognostic factor at primary diagnosis. In this article we briefly summarize recent studies examining the presence of circulating tumor cells in the blood and discuss further clinical applications.     

Transcriptional profiling of circulating tumor cells: quantification and cancer progression (Review)

Circulating tumor cells in peripheral blood have been demonstrated to reflect the biological characteristics of tumors including the potential for metastasis development and tumor recurrence. A number of mRNA markers may feasibly enable the detection of circulating tumor cells from virtually all patients with different cancer types. Of clinical relevance, quantification of circulating tumor cell mRNAs in cancer patients may prove valuable for monitoring disease progression and patients' response to treatment, and assessing the risk for metastasis or recurrence. With prognostic implications, the quantities of mRNA markers in blood could indicate the stage of cancer progression and the need for more intensive therapeutic intervention to better the outcome of cancer patients.