BTC, biliary tract cancer

BTC,胆道癌
  • 文章类型: Journal Article
    驱动蛋白家族成员20A(KIF20A)是驱动蛋白家族的成员。它在有丝分裂期间运输染色体,在细胞分裂中起着关键作用。最近,研究证明KIF20A在癌症中高表达。KIF20A的高表达与低总生存期(OS)相关。在这次审查中,我们总结了所有高表达KIF20A的癌症,描述了KIF20A在癌症中的作用。我们还组织了KIF20A肽疫苗的I期和II期临床试验。所有结果表明KIF20A是多种癌症的有希望的治疗靶标。
    Kinesin family member 20A (KIF20A) is a member of the kinesin family. It transports chromosomes during mitosis, plays a key role in cell division. Recently, studies proved that KIF20A was highly expressed in cancer. High expression of KIF20A was correlated with poor overall survival (OS). In this review, we summarized all the cancer that highly expressed KIF20A, described the role of KIF20A in cancer. We also organized phase I and phase II clinical trials of KIF20A peptides vaccine. All results indicated that KIF20A was a promising therapeutic target for multiple cancer.
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  • 文章类型: Journal Article
    未经证实:胆道癌(BTC)与预后不良有关,部分原因是它通常被诊断为晚期,强调对诊断性生物标志物的需求。该项目的目的是鉴定和验证可以区分BTC患者与非癌症对照的多蛋白特征。
    未经批准:在这项研究中,我们包括未接受BTC治疗的患者,健康的控制,以及良性疾病包括良性胆道疾病的患者。参与者分为三个不重叠的队列:基于病例对照的发现队列(BTC=186,对照=249);基于病例对照的验证队列(验证队列1:BTC=113,对照=241);以及基于队列研究的验证队列,其中包括参与者(BTC=8,对照=132),用于疑似癌症的诊断检查(验证队列2)。使用邻近延伸测定(Olink蛋白质组学)在血清和血浆中测量免疫肿瘤学(I-O)相关蛋白。套索和里奇回归用于在发现队列中产生I-O相关蛋白质和碳水化合物抗原19-9(CA19-9)的蛋白质特征。
    未经证实:十六个蛋白质特征,包括2到82种蛋白质,产生了。所有特征包括CA19-9和趋化因子C-C基序配体20。BTC患者与BTC患者之间的区别特征controls,发现队列的AUC范围为0.95至0.99,验证队列1的AUC范围为0.94至0.97。在验证队列2中,AUC范围为0.84至0.94。在验证队列2中,9个签名实现82%至84%的特异性,同时保持100%的灵敏度。所有特征表现优于CA19-9,并且包括>15种蛋白质的特征表现出最佳性能。
    UNASSIGNED:该研究表明,有可能产生可以成功区分BTC患者与非癌症对照的蛋白质特征。
    UNASSIGNED:我们试图寻找基于血液样本的蛋白质谱,以区分患有胆道癌的患者和没有癌症的患者。在不同组的患者中发现并测试了几种概况。这些资料成功地识别了大多数胆道癌患者,指出多蛋白签名在这种情况下的实用性。
    UNASSIGNED: Biliary tract cancer (BTC) is associated with a dismal prognosis, partly because it is typically diagnosed late, highlighting the need for diagnostic biomarkers. The purpose of this project was to identify and validate multiprotein signatures that could differentiate patients with BTC from non-cancer controls.
    UNASSIGNED: In this study, we included treatment-naïve patients with BTC, healthy controls, and patients with benign conditions including benign biliary tract disease. Participants were divided into three non-overlapping cohorts: a case-control-based discovery cohort (BTC = 186, controls = 249); a case-control-based validation cohort (validation cohort 1: BTC = 113, controls = 241); and a cohort study-based validation cohort including participants (BTC = 8, controls = 132) referred for diagnostic work-up for suspected cancer (validation cohort 2). Immuno-Oncology (I-O)-related proteins were measured in serum and plasma using a proximity extension assay (Olink Proteomics). Lasso and Ridge regressions were used to generate protein signatures of I-O-related proteins and carbohydrate antigen 19-9 (CA19-9) in the discovery cohort.
    UNASSIGNED: Sixteen protein signatures, including 2 to 82 proteins, were generated. All signatures included CA19-9 and chemokine C-C motif ligand 20. Signatures discriminated between patients with BTC vs. controls, with AUCs ranging from 0.95 to 0.99 in the discovery cohort and 0.94 to 0.97 in validation cohort 1. In validation cohort 2, AUCs ranged from 0.84 to 0.94. Nine signatures achieved a specificity of 82% to 84% while keeping a sensitivity of 100% in validation cohort 2. All signatures performed better than CA19-9, and signatures including >15 proteins showed the best performance.
    UNASSIGNED: The study demonstrated that it is possible to generate protein signatures that can successfully differentiate patients with BTC from non-cancer controls.
    UNASSIGNED: We attempted to find blood sample-based protein profiles that could differentiate patients with biliary tract cancer from those without cancer. Several profiles were found and tested in different groups of patients. The profiles were successful at identifying most patients with biliary tract cancer, pointing towards the utility of multiprotein signatures in this context.
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  • 文章类型: Journal Article
    胆道癌(BTC)是侵袭性上皮恶性肿瘤,可在胆道树的任何部位出现。尽管很罕见,在过去的40年里,它们的发病率和死亡率一直在稳步上升,强调需要改进当前的诊断和治疗策略。BTC在形态和分子水平上都显示出高的肿瘤间和肿瘤内异质性。这种复杂的异质性对有效的干预措施构成了实质性障碍。人们普遍认为,观察到的异质性可能是不同元素复杂相互作用的结果,包括风险因素,不同的分子改变和多个潜在的起源细胞。在实验模型中使用遗传谱系追踪系统已经确定了胆管细胞,肝细胞和/或祖细胞样细胞作为BTC的起源细胞。支持不同起源细胞假说的基因组证据正在增加。在这次审查中,我们关注BTC组织病理学亚型的最新进展,讨论当前的基因组证据,并概述谱系追踪研究,这些研究有助于围绕这些肿瘤的起源细胞的当前知识。
    Biliary tract cancers (BTCs) are aggressive epithelial malignancies that can arise at any point of the biliary tree. Albeit rare, their incidence and mortality rates have been rising steadily over the past 40 years, highlighting the need to improve current diagnostic and therapeutic strategies. BTCs show high inter- and intra-tumour heterogeneity both at the morphological and molecular level. Such complex heterogeneity poses a substantial obstacle to effective interventions. It is widely accepted that the observed heterogeneity may be the result of a complex interplay of different elements, including risk factors, distinct molecular alterations and multiple potential cells of origin. The use of genetic lineage tracing systems in experimental models has identified cholangiocytes, hepatocytes and/or progenitor-like cells as the cells of origin of BTCs. Genomic evidence in support of the distinct cell of origin hypotheses is growing. In this review, we focus on recent advances in the histopathological subtyping of BTCs, discuss current genomic evidence and outline lineage tracing studies that have contributed to the current knowledge surrounding the cell of origin of these tumours.
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  • 文章类型: Journal Article
    背景:胆道癌(BTC)的诊断在临床实践中具有挑战性。我们进行了一项前瞻性研究,以评估血浆拷贝数变异(CNV)测定在诊断BTC中的价值。
    方法:纳入47例可疑胆道病变的初治患者。在入院时收集血浆样品。通过低覆盖率全基因组测序分析无细胞DNA,然后通过定制的生物信息学工作流程进行CNV分析,即超敏染色体非整倍体检测器。
    结果:29例患者病理诊断为BTC,包括8例胆囊癌(GBC)和21例胆管癌(CC)。与良性患者相比,癌症患者的CNV信号更多(26/29vs.2/18,P<0.001)。最频繁的拷贝数增益是chr3q(7/29)和chr8q(6/29)。最常见的拷贝数损失是chr7p(6/29),chr17p(6/29),和chr19p(6/29)。血浆CNV检测诊断BTC的敏感性和特异性分别为89.7%和88.9%,分别。对于CA19-9(截止:37U/ml),敏感性为58.6%,特异性为72.2%.CNV检测的诊断准确性显著优于CA19-9(AUC0.91vs.0.62,P=0.004)。与单独的CA19-9相比,在CA19-9中添加CNV谱增加了诊断GBC的敏感性(75.0%vs.25.0%)和CC(100%与52.4%)。较高的CNV负荷也与总生存率降低相关(危险比=4.32,95%CI2.06-9.08,P=0.033)。
    结论:我们的结果表明,BTC具有丰富的血浆CNV信号,和他们的检测可能是有用的诊断BTC。
    BACKGROUND: The diagnosis of biliary tract cancer (BTC) is challenging in clinical practice. We performed a prospective study to evaluate the value of plasma copy number variation (CNV) assays in diagnosing BTC.
    METHODS: 47 treatment-naïve patients with suspicious biliary lesions were recruited. Plasma samples were collected at admission. Cell-free DNA was analyzed by low coverage whole genome sequencing, followed by CNV analyses via a customized bioinformatics workflow, namely the ultrasensitive chromosomal aneuploidy detector.
    RESULTS: 29 patients were pathologically diagnosed as BTC, including 8 gallbladder cancers (GBCs) and 21 cholangiocarcinomas (CCs). Cancer patients had more CNV signals as compared with benign patients (26/29 vs. 2/18, P < 0.001). The most frequent copy number gains were chr3q (7/29) and chr8q (6/29). The most frequent copy number losses were chr7p (6/29), chr17p (6/29), and chr19p (6/29). The sensitivity and specificity of plasma CNV assays in diagnosing BTC were 89.7% and 88.9%, respectively. For CA 19-9 (cutoff: 37 U/ml), the sensitivity was 58.6% and the specificity was 72.2%. The diagnostic accuracy of CNV assays significantly outperformed CA 19-9 (AUC 0.91 vs. 0.62, P = 0.004). Compared with CA 19-9 alone, the adding of CNV profiles to CA 19-9 increased the sensitivity in diagnosing GBC (75.0% vs. 25.0%) and CC (100% vs. 52.4%). Higher CNV burden was also associated with decreased overall survival (Hazard ratio = 4.32, 95% CI 2.06-9.08, P = 0.033).
    CONCLUSIONS: Our results suggest that BTC harbors rich plasma CNV signals, and their assays might be useful for diagnosing BTC.
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  • 文章类型: Journal Article
    OBJECTIVE: Surgical resection is the only potentially curative therapy for patients with biliary tract cancer (BTC), but 5-year survival rates after tumor resection have remained below 30%, corroborating the need for better stratification tools to identify the ideal surgical candidates. The soluble urokinase plasminogen activator receptor (suPAR) represents a mediator of inflammation and has been associated with distinct types of cancer. In this study, we evaluated a potential role of suPAR as a novel biomarker in patients undergoing BTC resection.
    METHODS: Tumor expression of uPAR was analyzed by immunohistochemistry in 108 BTC samples. Serum levels of suPAR were analyzed by ELISA in a training and validation cohort comprising a total of 117 patients with BTC and 76 healthy controls.
    RESULTS: High tumoral uPAR expression was associated with an adverse outcome after BTC resection. Accordingly, circulating levels of suPAR were significantly elevated in patients with BTC compared to healthy controls, as well as in patients with primary sclerosing cholangitis. Using a small training set, we established an optimal prognostic suPAR cut-off value of 3.72 ng/ml for patients with BTC. Importantly, preoperative suPAR serum levels above this cut-off value were associated with significantly impaired overall survival in both the training and validation cohort. Multivariate Cox-regression analysis including various clinicopathological parameters such as tumor stage, markers of inflammation and organ dysfunction, as well as tumor markers, revealed circulating suPAR levels as an independent prognostic marker following BTC resection. Finally, high preoperative suPAR levels were indicative of acute kidney injury after tumor resection.
    CONCLUSIONS: Circulating suPAR represents a previously unrecognized biomarker in patients with resectable BTC, which might help to preoperatively identify the ideal candidates for liver surgery.
    BACKGROUND: Surgical resection represents the only curative treatment option for patients with biliary tract cancer, but not all patients benefit to the same extent in terms of overall survival. Here, we provide evidence that serum levels of an inflammatory mediator (suPAR) are indicative of a patient\'s postoperative outcome and might thus help to identify the ideal surgical candidates.
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