cancer biomarkers

癌症生物标志物
  • 文章类型: Journal Article
    乳腺癌是女性最常见的癌症,也是全球女性癌症死亡的主要原因。因此,了解与乳腺癌发展和进展相关的分子机制,包括耐药性和乳腺癌转移,对于实现乳腺癌患者的最佳管理至关重要。已显示癌症相关的长链非编码RNA参与乳腺癌进展的每个阶段的调节。此外,外泌体是细胞外微泡,是细胞间通讯的核心,在肿瘤发生中起着重要作用。外泌体可以从原代肿瘤细胞释放到血流中,并将细胞信号传递到远处的身体部位。在这项工作中,我们回顾了关于外泌体lncRNAs调控的细胞机制的发现,这些机制是乳腺癌化疗耐药发展和转移的基本要素。同样,我们评估了外泌体lncRNAs作为乳腺癌生物标志物用于实现患者个性化管理的潜在临床应用结果.这一发现强调了外泌体lncRNAs的转录组学分析对了解乳腺癌肿瘤发生以及改善该疾病可用的临床试验的重要性。
    Breast cancer is the most common cancer in women and the leading cause of female deaths by cancer in the world worldwide. Hence, understanding the molecular mechanisms associated with breast cancer development and progression, including drug resistance and breast cancer metastasis, is essential for achieving the best management of breast cancer patients. Cancer-related long noncoding RNAs have been shown to be involved in the regulation of each stage of breast cancer progression. Additionally, exosomes are extracellular microvesicles that are central to intercellular communication and play an important role in tumorigenesis. Exosomes can be released from primary tumor cells into the bloodstream and transmit cellular signals to distant body sites. In this work, we review the findings regarding the cellular mechanisms regulated by exosomal lncRNAs that are essentials to chemoresistance development and metastasis of breast cancer. Likewise, we evaluate the outcomes of the potential clinical use of exosomal lncRNAs as breast cancer biomarkers to achieve personalized management of the patients. This finding highlights the importance of transcriptomic analysis of exosomal lncRNAs to understand the breast cancer tumorigenesis as well as to improve the clinical tests available for this disease.
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  • 文章类型: Journal Article
    膜转运蛋白是负责促进分子在生物膜内运动的蛋白质。它们通过调节营养物质的运输在维持细胞稳态方面发挥着至关重要的作用,离子,和其他分子进出细胞。我们的目的是使用膜转运蛋白鉴定结直肠癌中的生物标志物。为此,我们使用了COADTCGA数据。随后,我们使用膜转运蛋白进行了差异基因分析和特征选择。此外,我们确定了两个潜在的基因,包括ANO7和SLC38A4。为了验证ANO7和SLC38A4的表达谱,在这种情况下,关键基因,对结肠直肠癌样品和邻近的正常组织采用RT-qPCR。此外,利用GEPIA2,Kaplan-Meier生存分析,和cBioPortal,我们评估了这些基因在各种癌症中的状态,检查它们的甲基化和突变模式。总之,我们建议ANO7和SLC38A4可作为结直肠癌的预后生物标志物.
    Membrane transporters are proteins responsible for facilitating the movement of molecules within biological membranes. They play a vital role in maintaining cellular homeostasis by regulating the transport of nutrients, ions, and other molecules into and out of cells. Our aim is to identify biomarkers in colorectal cancer using membrane transporter proteins. We utilized COAD TCGA data for this purpose. Subsequently, we conducted differential gene analysis and feature selection using membrane transporter proteins. Furthermore, we identified two potential genes, including ANO7 and SLC38A4. To validate the expression profiles of ANO7 and SLC38A4, key genes in this context, RT-qPCR was employed on colorectal cancer samples and adjacent normal tissues. Additionally, utilizing GEPIA2, Kaplan-Meier survival analysis, and cBioPortal, we assessed the status of these genes in various cancers, examining their methylation and mutation patterns. In conclusion, we suggest that ANO7 and SLC38A4 serve as prognostic biomarkers in colorectal cancer.
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  • 文章类型: Journal Article
    外泌体是众所周知的细胞外囊泡,通过分布必需的大分子如蛋白质来促进细胞与细胞的通讯,DNA,mRNA脂质,和miRNA。这些囊泡富含分布在全身的液体中,包括尿液,血,唾液,甚至胆汁。它们是乳房的重要诊断工具,肺,胃肠道癌症,等。然而,它们作为癌症生物标志物的应用尚未在世界大多数地区实施。在这次审查中,我们讨论了如何通过替代传统的成像或活检方法来进行外泌体的OMIC分析来进行癌症检测.以前的方法,如广泛的成像和活检用于筛查是昂贵的,主要是侵入性的,并且无法轻易提供各种类型癌症的早期检测。通过简单地从个体收集体液,外来体生物标志物可用于常规筛选。我们预计,外泌体的使用将被临床试验的成功发现,这些临床试验研究了它们在未来几年增强癌症检测和治疗的潜力。
    Exosomes are extracellular vesicles well known for facilitating cell-to-cell communication by distributing essential macromolecules like proteins, DNA, mRNA, lipids, and miRNA. These vesicles are abundant in fluids distributed throughout the body, including urine, blood, saliva, and even bile. They are important diagnostic tools for breast, lung, gastrointestinal cancers, etc. However, their application as cancer biomarkers has not yet been implemented in most parts of the world. In this review, we discuss how OMICs profiling of exosomes can be practiced by substituting traditional imaging or biopsy methods for cancer detection. Previous methods like extensive imaging and biopsy used for screening were expensive, mostly invasive, and could not easily provide early detection for various types of cancer. Exosomal biomarkers can be utilized for routine screening by simply collecting body fluids from the individual. We anticipate that the use of exosomes will be brought to light by the success of clinical trials investigating their potential to enhance cancer detection and treatment in the upcoming years.
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  • 文章类型: Journal Article
    肝细胞癌是目前肝脏最常见的恶性肿瘤。它通常是由于导致细胞复制异常的一系列致癌突变而发生的。最常见的是,肝细胞癌(HCC)的发生是由于预先发生的肝病,如肝炎和肝硬化。鉴于其侵袭性和不良预后,肝癌的早期筛查和诊断至关重要。然而,由于其过多的潜在风险因素和病理生理,患者的表现在早期阶段往往有所不同,许多患者很少,如果有的话,在早期阶段的特定症状。传统上,筛查和诊断是通过放射学检查进行的,活检证实诊断。成像模式往往受到其要求的限制,昂贵的设备;耗时的操作;缺乏准确的诊断,而活检的侵入性使得它对重复使用没有吸引力。最近,生物传感器因其快速检测多种条件的潜力而受到关注,便宜,准确地说,没有复杂的设备和培训。通过他们的传感平台,他们的目标是检测各种生物标志物,如核酸,蛋白质,甚至是液体活检提取的完整细胞。已经开发了许多生物传感器,可以在早期阶段检测HCC。我们讨论生物传感技术的最新进展,突出了与传统方法相比的竞争潜力及其作为筛查和诊断工具的前景。
    Hepatocellular carcinoma is currently the most common malignancy of the liver. It typically occurs due to a series of oncogenic mutations that lead to aberrant cell replication. Most commonly, hepatocellular carcinoma (HCC) occurs as a result of pre-occurring liver diseases, such as hepatitis and cirrhosis. Given its aggressive nature and poor prognosis, the early screening and diagnosis of HCC are crucial. However, due to its plethora of underlying risk factors and pathophysiologies, patient presentation often varies in the early stages, with many patients presenting with few, if any, specific symptoms in the early stages. Conventionally, screening and diagnosis are performed through radiological examination, with diagnosis confirmed by biopsy. Imaging modalities tend to be limited by their requirement of large, expensive equipment; time-consuming operation; and a lack of accurate diagnosis, whereas a biopsy\'s invasive nature makes it unappealing for repetitive use. Recently, biosensors have gained attention for their potential to detect numerous conditions rapidly, cheaply, accurately, and without complex equipment and training. Through their sensing platforms, they aim to detect various biomarkers, such as nucleic acids, proteins, and even whole cells extracted by a liquid biopsy. Numerous biosensors have been developed that may detect HCC in its early stages. We discuss the recent updates in biosensing technology, highlighting its competitive potential compared to conventional methodology and its prospects as a tool for screening and diagnosis.
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  • 文章类型: Journal Article
    这篇综述全面探讨了细胞外囊泡(ECVs)/外泌体与昼夜节律之间的复杂相互作用,重点关注这种相互作用在肝细胞癌(HCC)中的作用。外泌体是来自细胞的纳米囊泡,通过运输生物活性分子如蛋白质,促进细胞间的通讯,脂质,和RNA/DNA物种。ECV与一系列疾病有关,它们在细胞和周围环境之间的信号传导中起着至关重要的作用。在癌症的背景下,已知ECV影响癌症的开始和进展。本综述的范围扩展到所有癌症类型,综合现有的关于ECV各种角色的知识。本综述的一个独特方面是强调外泌体的昼夜节律控制释放和组成,突出了它们作为早期癌症检测和监测转移的生物标志物的潜力。我们还讨论了昼夜节律如何影响多种癌症相关途径,提出生物钟的中断可以改变肿瘤的发展和治疗反应。此外,本文综述了生物钟成分对ECV生物发生的影响及其对重塑肿瘤微环境的影响,驱动HCC进展的关键组成部分。最后,我们讨论了ECV的潜在临床应用,特别是它们用作诊断工具和药物输送工具,同时考虑与临床实施相关的挑战。
    This review comprehensively explores the complex interplay between extracellular vesicles (ECVs)/exosomes and circadian rhythms, with a focus on the role of this interaction in hepatocellular carcinoma (HCC). Exosomes are nanovesicles derived from cells that facilitate intercellular communication by transporting bioactive molecules such as proteins, lipids, and RNA/DNA species. ECVs are implicated in a range of diseases, where they play crucial roles in signaling between cells and their surrounding environment. In the setting of cancer, ECVs are known to influence cancer initiation and progression. The scope of this review extends to all cancer types, synthesizing existing knowledge on the various roles of ECVs. A unique aspect of this review is the emphasis on the circadian-controlled release and composition of exosomes, highlighting their potential as biomarkers for early cancer detection and monitoring metastasis. We also discuss how circadian rhythms affect multiple cancer-related pathways, proposing that disruptions in the circadian clock can alter tumor development and treatment response. Additionally, this review delves into the influence of circadian clock components on ECV biogenesis and their impact on reshaping the tumor microenvironment, a key component driving HCC progression. Finally, we address the potential clinical applications of ECVs, particularly their use as diagnostic tools and drug delivery vehicles, while considering the challenges associated with clinical implementation.
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  • 文章类型: Journal Article
    灌注动力学在向组织输送必需营养素和氧气同时去除代谢废物中起着至关重要的作用。成像技术,如磁共振成像(MRI),计算机断层扫描(CT),和正电子发射断层扫描(PET)使用造影剂来可视化灌注和清除模式;然而,每种技术都有特定的局限性。混合PET/MRI将PET的定量功率和灵敏度与MRI的高功能和解剖学细节相结合,并在分子成像中具有很好的精度。然而,具有挑战性的合成和放射性标记阻碍了双PET/MRI探针的开发。这里,我们提出了一种新型的PET/MRI探头,[18F][Gd(FL1)],与临床实践中使用的大环MRI造影剂相比,具有出色的稳定性。[18F][Gd(FL1)]的独特分子设计允许在最终合成步骤中选择性和迅速地放射性标记钆螯合物。利用MRI和PET信号的优势,该探针能够通过创新的基于体素的分析定量体内灌注和排泄动力学作图。在对健康小鼠的初步研究中证明了[18F][Gd(FL1)]的诊断能力,成功发现早期单侧肾功能不全病例。这项研究为PET/MRI引入了一种新方法,并强调了简化的探头设计,以提高诊断准确性。
    Perfusion dynamics play a vital role in delivering essential nutrients and oxygen to tissues while removing metabolic waste products. Imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) use contrast agents to visualize perfusion and clearance patterns; however, each technique has specific limitations. Hybrid PET/MRI combines the quantitative power and sensitivity of PET with the high functional and anatomical detail of MRI and holds great promise for precision in molecular imaging. However, the development of dual PET/MRI probes has been hampered by challenging synthesis and radiolabeling. Here, we present a novel PET/MRI probe, [18F][Gd(FL1)], which exhibits excellent stability comparable to macrocyclic MRI contrast agents used in clinical practice. The unique molecular design of [18F][Gd(FL1)] allows selective and expeditious radiolabeling of the gadolinium chelate in the final synthetic step. Leveraging the strengths of MRI and PET signals, the probe enables quantitative in vivo mapping of perfusion and excretion dynamics through an innovative voxel-based analysis. The diagnostic capabilities of [18F][Gd(FL1)] were demonstrated in a pilot study on healthy mice, successfully detecting early cases of unilateral renal dysfunction. This study introduces a new approach for PET/MRI and emphasizes a streamlined probe design for improved diagnostic accuracy.
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  • 文章类型: Journal Article
    介孔二氧化硅纳米颗粒(MSN)表现出高度有益的特性,可为不同的分析物设计有效的生物传感器。他们独特的属性,例如与识别基团稳定共价结合的能力(例如,抗体或适体)和传感表面,为生物传感器建设提供了大量机会。此外,它们的结构孔隙度提供了捕获信号分子(染料或电活性物质)的能力,其可以响应于用于有效的光学或电化学检测的所需分析物有效地释放。这项工作概述了最近的研究(过去五年),这些研究在其用于检测癌症生物标志物的光学和电化学传感平台中包含MSN,按癌症类型分类。此外,这项研究提供了癌症生物标志物的概述,以及一般的电化学和光学检测方法。
    Mesoporous silica nanoparticles (MSNs) exhibit highly beneficial characteristics for devising efficient biosensors for different analytes. Their unique properties, such as capabilities for stable covalent binding to recognition groups (e.g., antibodies or aptamers) and sensing surfaces, open a plethora of opportunities for biosensor construction. In addition, their structured porosity offers capabilities for entrapping signaling molecules (dyes or electroactive species), which could be released efficiently in response to a desired analyte for effective optical or electrochemical detection. This work offers an overview of recent research studies (in the last five years) that contain MSNs in their optical and electrochemical sensing platforms for the detection of cancer biomarkers, classified by cancer type. In addition, this study provides an overview of cancer biomarkers, as well as electrochemical and optical detection methods in general.
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  • 文章类型: Journal Article
    我们开发了一种用于检测和定量痕量核酸的技术,该技术使用包围方案,旨在在所有浓度中产生具有约±20%准确性的拷贝数。microRNAs(miRNAs)let-7b,miR-15b,在健康受试者和乳腺癌患者的血清和尿液样品中测量miR-21,miR-375和miR-141,前列腺癌或胰腺癌。检测和定量是无扩增的,并使用锇标记的探针和MinION,纳米孔阵列检测装置。来自健康男性的联合血清(Sigma-Aldrich,圣路易斯,MO,美国#H6914)用作参考。使用商业试剂盒从生物样本分离的总RNA用作miRNA来源。前所未有的±20%的准确性导致的结论是,miRNA拷贝数必须标准化为相同的RNA含量,这反过来说明(I)独立于年龄,性别和种族,以及(ii)血清和尿液之间的等效性。miR-21、miR-375和miR-141拷贝在癌症中有1.8倍的过表达。与健康样本显示零重叠,p值为1.6×10-22,初步验证了每种miRNA作为多癌生物标志物.miR-15b被证实与癌症无关,而let-7b似乎是前列腺癌和乳腺癌的癌症生物标志物,但不是胰腺癌。
    We developed a technology for detecting and quantifying trace nucleic acids using a bracketing protocol designed to yield a copy number with approximately ± 20% accuracy across all concentrations. The microRNAs (miRNAs) let-7b, miR-15b, miR-21, miR-375 and miR-141 were measured in serum and urine samples from healthy subjects and patients with breast, prostate or pancreatic cancer. Detection and quantification were amplification-free and enabled using osmium-tagged probes and MinION, a nanopore array detection device. Combined serum from healthy men (Sigma-Aldrich, St. Louis, MO, USA #H6914) was used as a reference. Total RNA isolated from biospecimens using commercial kits was used as the miRNA source. The unprecedented ± 20% accuracy led to the conclusion that miRNA copy numbers must be normalized to the same RNA content, which in turn illustrates (i) independence from age, sex and ethnicity, as well as (ii) equivalence between serum and urine. miR-21, miR-375 and miR-141 copies in cancers were 1.8-fold overexpressed, exhibited zero overlap with healthy samples and had a p-value of 1.6 × 10-22, tentatively validating each miRNA as a multi-cancer biomarker. miR-15b was confirmed to be cancer-independent, whereas let-7b appeared to be a cancer biomarker for prostate and breast cancer, but not for pancreatic cancer.
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  • 文章类型: Journal Article
    透明细胞肾细胞癌(ccRCC),一种以侵袭性和异质性为特征的普遍肾癌形式,在晚期预后和治疗结果方面提出了挑战。程序性细胞死亡机制,对消除癌细胞至关重要,提供对恶性肿瘤诊断的实质性见解,治疗和预后。本研究旨在提供一种基于15种类型的程序性细胞死亡相关基因(PCDRGs)的模型,用于评估ccRCC患者的免疫微环境和预后。来自TCGA和arrayexpress队列的ccRCC患者基于PCDRGs进行分组。构建了使用Lasso和SuperPC的组合模型来识别预后基因特征。arrayexpress队列验证了该模型,确认其稳健性。免疫微环境分析,在PCDRG的推动下,采用了各种方法,包括CIBERSORT。药物敏感性分析指导临床治疗决策。单细胞数据启用程序性细胞死亡相关评分,随后的伪时间和小区通信分析。使用TCGA-KIRC数据建立PCDRGs签名。arrayexpress队列中的外部验证强调了该模型优于传统临床特征。此外,我们的单细胞分析揭示了基于PCDRG的单细胞亚群在ccRCC中的作用,在伪时间进展和细胞间通讯方面。最后,我们进行了CCK-8测定和其他实验来研究csf2。总之,这些发现表明csf2抑制了生长,肾透明细胞癌相关细胞的浸润和运动。这项研究引入了PCDRGs预后模型,使ccRCC患者受益,同时阐明了程序性细胞死亡基因在塑造ccRCC患者免疫微环境中的关键作用。
    Clear cell renal cell carcinoma (ccRCC), a prevalent kidney cancer form characterised by its invasiveness and heterogeneity, presents challenges in late-stage prognosis and treatment outcomes. Programmed cell death mechanisms, crucial in eliminating cancer cells, offer substantial insights into malignant tumour diagnosis, treatment and prognosis. This study aims to provide a model based on 15 types of Programmed Cell Death-Related Genes (PCDRGs) for evaluating immune microenvironment and prognosis in ccRCC patients. ccRCC patients from the TCGA and arrayexpress cohorts were grouped based on PCDRGs. A combination model using Lasso and SuperPC was constructed to identify prognostic gene features. The arrayexpress cohort validated the model, confirming its robustness. Immune microenvironment analysis, facilitated by PCDRGs, employed various methods, including CIBERSORT. Drug sensitivity analysis guided clinical treatment decisions. Single-cell data enabled Programmed Cell Death-Related scoring, subsequent pseudo-temporal and cell-cell communication analyses. A PCDRGs signature was established using TCGA-KIRC data. External validation in the arrayexpress cohort underscored the model\'s superiority over traditional clinical features. Furthermore, our single-cell analysis unveiled the roles of PCDRG-based single-cell subgroups in ccRCC, both in pseudo-temporal progression and intercellular communication. Finally, we performed CCK-8 assay and other experiments to investigate csf2. In conclusion, these findings reveal that csf2 inhibit the growth, infiltration and movement of cells associated with renal clear cell carcinoma. This study introduces a PCDRGs prognostic model benefiting ccRCC patients while shedding light on the pivotal role of programmed cell death genes in shaping the immune microenvironment of ccRCC patients.
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  • 文章类型: Journal Article
    富马酸水合酶(FH)缺乏的肾细胞癌是罕见的肿瘤,其特征是FH基因具有广泛的形态学异质性和致病性突变。它们经常表现出攻击行为,快速扩散到远处的器官,所以新的治疗方案已经被探索,包括EGFR抑制剂和PD-L1表达用于靶向免疫治疗。在这里,我们调查了11例原发性FH缺乏的肾细胞癌和7例远处转移瘤,以评估肿瘤异质性,甚至在转移部位,并估计向不同器官的特定扩散率.此外,对肿瘤进行了免疫组织化学PD-L1表达和EGFR突变检测.大多数转移病例涉及腹部淋巴结(4/7,57%),其次是腹膜(3/7,42%),肝脏(2/7,29%),和肺(1/7,14%)。在组织学上记录了六个转移灶,揭示形态异质性结构通常与相应的原发性肾肿瘤不同。腹膜受累在形态上类似于良性反应性间皮瘤或原发性腹膜间皮瘤,因此主张进行准确的免疫组织化学小组,包括PAX8和FH,达到正确的诊断。还记录了纯的低级别SDH型原发性FH缺乏的肾细胞癌。至于治疗,在60%的原发性肾脏肿瘤中发现了显着的PD-L1标记,而他们都没有携带致病性EGFR突变。我们的数据表明,FH缺乏的肾细胞癌在转移中也可能在形态上异质,涉及淋巴结,肝脏,和腹膜比其他肾肿瘤更常见。由于后者的频率很高(42%),病理学家应该总是关心排除间皮组织衍生的模数,以及罕见的初级低品位类型的出现。最后,与EGFR突变相反,PD-L1表达可能是治疗这些肿瘤的可能的预测生物标志物。
    Fumarate hydratase (FH)-deficient renal cell carcinomas are rare neoplasms characterized by wide morphologic heterogeneity and pathogenetic mutations in the FH gene. They often show aggressive behavior with rapid diffusion to distant organs, so novel therapeutic scenarios have been explored, including EGFR inhibitors and PD-L1 expression for targeted immunotherapy. Herein, we investigated a series of 11 primary FH-deficient renal cell carcinomas and 7 distant metastases to evaluate tumor heterogeneity even in metastatic sites and estimate the specific spread rates to various organs. Furthermore, the tumors were tested for immunohistochemical PD-L1 expression and EGFR mutations. Most metastatic cases involved the abdominal lymph nodes (4/7; 57%), followed by the peritoneum (3/7; 42%), the liver (2/7; 29%), and the lungs (1/7; 14%). Six metastatic localizations were histologically documented, revealing a morphologic heterogeneous architecture often differing from that of the corresponding primary renal tumor. Peritoneal involvement morphologically resembled a benign reactive mesothelial process or primary peritoneal mesothelioma, thus advocating to perform an accurate immunohistochemical panel, including PAX8 and FH, to reach a proper diagnosis. A pure low-grade succinate dehydrogenase-looking primary FH-deficient renal cell carcinoma was also recorded. As for therapy, significant PD-L1 labeling was found in 60% of primary renal tumors, whereas none of them carried pathogenetic EGFR mutations. Our data show that FH-deficient renal cell carcinoma may be morphologically heterogeneous in metastases as well, which involve the lymph nodes, the liver, and the peritoneum more frequently than other renal tumors. Due to the high frequency of this latter (42%), pathologists should always be concerned about ruling out mesothelial-derived mimickers, and the occurrence of rarer, primary, low-grade-looking types. Finally, contrary to EGFR mutations, PD-L1 expression could be a possible predictive biomarker for the therapy of these tumors.
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