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《科学》子刊徐瑞华团队发现全新肠癌血检标志物
2020-01-08 01:39   来源:  www.yaya-resort.com   评论:0 点击:

《科学》子刊徐瑞华团队发现全新肠癌血检标志物结直肠癌是全球致死率排行第三的消化道恶性肿瘤。我国每年新

结直肠癌是全球致死率排行第三的消化道恶性肿瘤。我国每年新发病例约40万,并且发病率逐年上升。结直肠癌的早期症状不明显,容易归结于生活习惯而被忽视,多数患者诊断时已为中晚期,手术和化疗后存活率依然较低。因此,高效普遍的结直肠癌诊断手段对疾病的预后和治疗至关重要。

Colorectal cancer is the third most fatal cancer of the digestive tract. The incidence of new cases in our country is about 400,000 per year, and the incidence is increasing year by year. The early symptoms of colorectal cancer are not obvious, it is easy to attribute to living habits and neglect, most patients have been diagnosed in the middle and late stages, and the survival rate after surgery and chemotherapy is still low. therefore, efficient universal diagnosis of colorectal cancer is crucial for the prognosis and treatment of the disease.

目前,肠镜是临床检查结直肠病变最直观有效的方法,但这种侵入性的检测具有费时、昂贵、患者依从性低等缺陷。液体活检是一项新兴的肿瘤检测手段,以血液等非固态生物组织为标本的分析来进行体外诊断。临床已有应用血清癌胚抗原(CEA)的结直肠癌生物标志物检测,但仅能检出40%-60%患者,灵敏度低。中山大学徐瑞华教授课题组于1月1日在ScienceTranslationalMedicine杂志上发表结果,发现可用于液体活检的特定ctDNA甲基化位点,为高效便捷的结直肠癌诊断和预后开辟非侵入性的新方法!

at present, enteroscopy is the most intuitive and effective method for clinical examination of colorectal lesions, but this invasive detection has time-consuming, expensive, low patient compliance and other defects. Liquid biopsy is a new method of tumor detection, which is based on the analysis of non-solid biological tissue such as blood for in vitro diagnosis. Colorectal cancer biomarkers of serum carcinoembryonic antigen (CEA) have been used in clinic, but only 40% to 60% of patients can be detected with low sensitivity. Professor Xu Ruihua of Sun Yat-sen University, published in the journal ScienceTransational Medicine on January 1, found specific ctDNA methylation sites that can be used for liquid biopsy, and opened up non-invasive new methods for efficient and convenient diagnosis and prognosis of colorectal cancer!

(中山大学肿瘤防治中心骆卉妍副主任医师、赵齐副研究员、韦玮主任医师等为文章的第一作者,徐瑞华教授是文章的通讯作者。)

Professor Xu Ruihua is the co-author of the article, including deputy chief physician of the Cancer Prevention and Treatment Center of Zhongshan University, associate researcher Zhao Qi and chief physician Wei Wei. )

循环肿瘤DNA(circulatingtumorDNA,ctDNA)是肿瘤细胞坏死或凋亡后释放到血液中的游离DNA(cfDNA)。作为肿瘤细胞碎片的一部分,cfDNA已经被深深打上特定来源的烙印,体现为肿瘤中特异性表达的突变基因以及表观遗传学异常。对cfDNA的分析和检测已发展成液体活检中的重要分支,具有不可估量的应用前景。

circulating tumor dna (ctdna) is free dna (cfdna) released into the blood after necrosis or apoptosis of tumor cells. as part of tumor cell fragments, cfdna has been deeply branded as a specific source, reflected in the specifically expressed mutant genes in tumors as well as epigenetic abnormalities. the analysis and detection of cfdna has been developed as an important branch in liquid biopsy with inestimable application prospects.

DNA甲基化是最常见的表观遗传学修饰,与分化发育、衰老等一系列生理病理过程相关;而抑癌基因的甲基化是肿瘤发生的早期标志之一。尽管SEPT9等位点已经被鉴定为结直肠癌cfDNA甲基化的标志性位点,然而由于患者个体差异以及体液cfDNA的含量较少,单一位点的甲基化检测准确性受到挑战。考虑到甲基转移酶或脱甲基酶可能会同时修饰同一条DNA链中相邻的CpG位点,对“甲基化相关嵌段”进行cfDNA甲基化图谱分析,将大大提高诊断等准确性。

DNA methylation is the most common epigenetic modification, which is related to a series of physiological and pathological processes such as differentiation and development, aging, and the methylation of tumor suppressor gene is one of the early markers of tumorigenesis. although sites such as sept9 have been identified as iconic sites for cfdna methylation in colorectal cancer, the accuracy of single-site methylation detection has been challenged due to patient individual differences and low body fluid cfdna content. considering that methyltransferase or demethylase may simultaneously modify adjacent cpg sites in the same dna strand, cfdna methylation profiling of “methylation-related blocks ” will greatly improve diagnostic and other accuracy.

首先,研究者收集结直肠癌患者的组织样本的全基因组筛查以及其cfDNA的甲基化数据,通过生物信息学分析鉴别了9个与结直肠癌发生相关的cfDNA甲基化标志物,依据算法建立的诊断分数(cd-score)预测来结直肠癌。将结直肠癌和健康受试者按2:1的比例分为建模组和验证组,发现结直肠癌诊断准确率高达96%,验证组诊断敏感性达%,特异性达%,远远超过临床应用的血清癌胚抗原CEA标志物的诊断效力。

first, researchers collected genome-wide screening of tissue samples from colorectal cancer patients and methylation data of their cfdna. bioinformatics analysis identified nine cfdna methylation markers associated with colorectal cancer occurrence, based on diagnostic scores established by the algorithm (cd-score) to predict colorectal cancer. colorectal cancer and healthy subjects were divided into modeling group and validation group at a ratio of 2:1. the diagnostic accuracy of colorectal cancer was up to 96%, and the diagnostic sensitivity of validation group was up to% and specificity was up to%, which far exceeded the diagnostic efficacy of serum cancer embryo antigen CEA markers for clinical application.

进而,研究者对900多名受试者进行为期平均个月的跟踪调查,结合肠镜和cfDNA甲基化数据,判别5个与结直肠癌预后有关的标志物;即通过对这些标志性甲基化位点的cp-score评分,几乎能准确推测出患者的生存率,远远优于临床常用的肿瘤原发部位、TMN分期、CEA等预后指标。

Furthermore, researchers tracked more than 900 subjects over an average period of time, combining colonoscopy and cfdna methylation data to identify five prognostic markers for colorectal cancer; that is, the cp-score score for these iconic methylation sites could almost accurately predict patient survival, far outperforming commonly used prognostic markers such as primary tumor site, tmn stage, and cea.

另外,在结直肠癌患者的cfDNA数据中,研究者们还发现依据45个甲基化差异显著的标志位点,可将结直肠癌分为两类,其中1型在女性中发病率更高并伴有左侧结肠病变,2型的存活率较低。这从分子层面鉴别了结直肠癌亚型,提示了内在生物学机制与临床病理进程的相关性。

In addition, in cfdna data from colorectal cancer patients, the researchers found that colorectal cancer was classified into two categories based on 45 marker sites with significant methylation differences. Type 1 was more common in women with left colon lesions and type 2 had a lower survival rate. this differentiates colorectal cancer subtypes from the molecular level, suggesting the correlation of intrinsic biological mechanisms with clinicopathological progression.

这项研究通过甲基化图谱分析,证明了一系列cfDNA的甲基化标志物用于结直肠癌诊断、预后和疾病检测中的准确性和灵敏度,为症状轻微的结直肠癌早期发现提供非侵入性的分子手段,具有极大的临床应用前景!

this study demonstrates the accuracy and sensitivity of a range of methylation markers of cfdna for colorectal cancer diagnosis, prognosis, and disease detection through methylation profiling, providing non-invasive molecular means for early detection of mildly symptomatic colorectal cancer with great clinical promise!

HuiyanLuo,etal.CirculatingtumorDNAmethylationprofilesenableearlydiagnosis,prognosisprediction,andscreeningforcolorectalcancer.ScienceTranslationalMedicine,01Jan,2020.


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