ABSTRACT
Cell cycle is one of the main cellular mechanisms involved in tumor progression. Almost all of the active molecular pathways in tumor cells directly or indirectly target the cell cycle progression. Therefore, it is necessary to assess the molecular mechanisms involved in cell cycle regulation in tumor cells. Since, early diagnosis has pivotal role in better cancer management and treatment, it is required to introduce the non-invasive diagnostic markers. Long non-coding RNAs (LncRNAs) have higher stability in body fluids in comparison with mRNAs. Therefore, they can be used as efficient non-invasive markers for the early detection of breast cancer (BCa). In the present review we have summarized all of the reported lncRNAs involved in cell cycle regulation in BCa. It has been reported that lncRNAs mainly affect the cell cycle in G1/S transition through the CCND1/CDK4-6 complex. Present review paves the way of introducing the cell cycle related lncRNAs as efficient markers for the early detection of BCa.
Subject(s)
Humans , Female , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Breast Neoplasms/pathology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Cell Cycle/genetics , Cell Division , Cell Cycle CheckpointsABSTRACT
@#Lung cancer is a malignant tumor with the highest mortality worldwide, and its early diagnosis and evaluation have a crucial impact on the comprehensive treatment of patients. Early preoperative diagnosis of lung cancer depends on a variety of imaging and tumor marker indicators, but it cannot be accurately assessed due to its high false positive rate. Liquid biopsy biomarkers can detect circulating tumor cells and DNA in peripheral blood by non-invasive methods and are gradually becoming a powerful diagnostic tool in the field of precision medicine for tumors. This article reviews the research progress of liquid biopsy biomarkers and their combination with clinical imaging features in the early diagnosis of lung cancer.
ABSTRACT
Liver cancer is the second largest cancer in China, with the majority being hepatocellular carcinoma(HCC), which has a significant adverse impact on the lives and health of the Chinese people. Liquid biopsy is a new type of examination method with peripheral blood as the main examination subject. Compared with conventional tumor tissue pathology, liquid biopsy has less trauma, and the detection items can more accurately represent a certain tumor tissue group, more directly reflect the biological behavior of tumor tissue in the patient′s body. It is widely used in tumor screening, staging and grading, tumor individualized treatment monitoring, and prognosis evaluation. The following is mainly about the diagnosis, therapeutic effect evaluation and prognosis prediction of liquid biopsy in HCC from three aspects: circulating tumor DNA (ctDNA), exosome and circulating tumor cells (CTC), and the challenges faced by liquid biopsy technology at present are briefly described and its future development is prospected.
ABSTRACT
Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Subject(s)
Humans , Female , Blood Platelets/pathology , Biomarkers, Tumor/genetics , Ovarian Neoplasms/pathology , ChinaABSTRACT
Precise classification of central nervous system (CNS) malignancies is vital for the treatment and prognostication. Identification of noninvasive markers can be of importance to guide treatment decisions and in monitoring treatment response. CNS tumors are classified based on morphology with an essential complement of molecular changes, including mutations, amplifications, and methylation. Neuroimaging is the mainstay for initial diagnosis and monitoring tumor response with obvious limitations of imprecise tumor typing and no information on diagnostic, predictive and prognostic markers. Liquid biopsy has evolved as a diagnostic tool in body fluids and is being investigated as a surrogate for tissue biopsy in managing primary and metastatic brain tumors. Liquid biopsy refers to analyzing biological fluids such as peripheral blood, urine, pleural effusion, ascites, and cerebrospinal fluid (CSF); however, peripheral blood remains the primary source of fluid biopsy. The analytes include cell-free DNA (cfDNA) circulating tumor cells (CTCs), circulating micro RNAs (miRNAs), circulating proteins and extracellular vesicles (EVs). Analysis of these components is actively used for early cancer detection, auxiliary staging, prognosis assessment, detection of minimal residual disease (MRD), and monitoring drug resistance in various solid tumors. In recent years, liquid biopsy has been studied in CNS tumors, and analysis of CTCs and cfDNA have become relevant research topics. In the current review, we have explained the clinical potential of liquid biopsy in CNS tumors to assist in diagnosing and predicting prognosis and response to treatment.
ABSTRACT
Lung cancer is one of the deadliest cancers globally and accounts for most of the cancer?related deaths in India. Comprehensive data on lung cancer in India are lacking. This review aimed to discuss the epidemiological trends of lung cancers and driver mutations as well as the recent advancements in molecular diagnostics and therapeutic options primarily in non杝mall cell lung cancer (NSCLC) in India. Electronic databases, such as PubMed and Google Scholar, were searched to retrieve the relevant literature published in the past 5 years. As per the GLOBOCAN 2018 report, lung cancer was ranked the fourth leading cause of cancer (5.9% cases) in India, in all ages and sexes. Furthermore, 63,475 of all cancer?related deaths (8.1%) were attributed to lung cancer (cumulative risk 0.60), making it the third leading cause of cancer?related mortality. The common targets for treatment in lung cancer patients mainly include EGFR mutation, ALK and ROS1 rearrangements and PDL1 expression. In India, EGFR mutations and ALK re?arrangement are commonly reported, but there is limited data of PD?L1 expression. Molecular testing has gained importance as several biomarkers are being targeted to treat lung cancer patients. Surgery, radiotherapy, systemic chemotherapy, and personalized molecular?targeted therapy prolong the overall survival (OS) in patients with NSCLC. Although chemotherapy and molecular?targeted therapies have greatly improved the clinical outcomes, prolonged disease control could not be attained in NSCLC patients without a driver mutation. In this situation, immunotherapy seems to be potentially beneficial to obtain long?lasting disease control with minimal adverse events.
ABSTRACT
@#With the improvement of computer computing capability and the accumulation of a large amount of medical data, artificial intelligence is gradually being applied in the diagnosis of oral and maxillofacial tumors. Artificial intelligence technology can assist doctors in clinical diagnosis and improve the efficiency of clinical work and the accuracy of diagnosis. In recent years, researchers have focused primarily on the recognition of medical images. The commonly used method is to annotate a large number of images by experts for learning image features by machines. The available literature has been able to utilize artificial intelligence technology to diagnose tumors by analyzing medical images, pathological sections, and tumor photos. The main issues in the current research are uneven labeling data quality, small data size, limited research problems, and single data modalities. These problems need to be solved through the continuous improvement of algorithms and the accumulation of high-quality data. The future direction of artificial intelligence applications should be to integrate medical data from multiple sources, assist doctors in diagnosis, and explore a variety of noninvasive and easy-to-use new methods for the early diagnosis of tumors. This may completely change the existing diagnosis and treatment model of oral and maxillofacial tumors.
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Neuroblastoma (NB) is the most common extracranial solid tumor in children and has the features of high recurrence rate and low survival rate, and therefore, early diagnosis, treatment response evaluation, and recurrence monitoring are of great significance for NB patients. Liquid biopsy refers to the detection of cells and nucleic acids in fluid specimens, mainly blood. It is noninvasive and can overcome tumor heterogeneity, thus making it possible to achieve the early diagnosis and dynamic detection of NB. This review introduces the latest advances in clinical research on the application of liquid biopsy in NB.
Subject(s)
Child , Humans , Liquid Biopsy , Neuroblastoma/diagnosisABSTRACT
Early diagnosis of hepatocellular carcinoma (HCC) is of great significance in the management of patients. Liquid biopsy is a promising tool to use for early diagnosis of liver cancer by detecting tumor expressions through analyzing circulating tumor components such as circulating tumor DNA, circulating tumor cells and extracellular vesicles. The advantages of using liquid biopsy include easy collection of specimen samples and its good sensitivity and specificity for HCC detection. In this review, recent research progress on liquid biopsy on HCC is discussed with the aim to provide updated information on early diagnosis of HCC.
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Gastric cancer is a common cancer in digestive system in China. It′s in the forefront of cancer in terms of morbidity and case fatality, posing a great threat to people′s health. With the advent of the era of precision medicine, the treatment of each patient with gastric cancer must follow the principle of individualization. However, individualized treatment is based on the development of biomarkers. Liquid biopsy has been reported to be a biomarker capable of detecting information about tumorigenesis and progression, and has been suggested as a useful tool for personalized treatment. Compared with traditional "tissue biopsy" , liquid biopsy has significant advantages because it is noninvasive and painless, reduces cost and time for diagnosis, and could be used for diagnosis, prognosis, prediction of disease progression, or as a surrogate marker of response to treatment.For this purpose, the author will review the related detection techniques of liquid biopsy and its role in early screening, efficacy evaluation and recurrence monitoring of gastric cancer.
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Lung cancer is one of the most malignant tumors in the world. In China, the mortality rate of lung cancer has been in the first place for many years. Early screening and early diagnosis of lung cancer is the premise of prolonging the survival time of patients with lung cancer. In recent years, liquid biopsy technology, which is considered to have a bright future, has attracted more and more attention, and its value in the early diagnosis of lung cancer is worth discussing. This paper reviews the application of biomarkers in early screening and early diagnosis of lung cancer, looks for specific biomarkers from multi-omics, and discusses their significance in early diagnosis of lung cancer.
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Pancreatic cancer (PC) is a highly malignant tumor of the digestive system. Due to the lack of sensitive and effective detection markers, the tumor is usually at a relatively advanced stage in initial diagnosis. Therefore, early detection of PC is crucial for timely treatment and better prognosis. Exosomes are extracellular vesicles secreted by cells. They have a lipid bimolecular membrane structure to ensure the stable existence of a large number of biologically active substances contained therein. So they can accurately reflect the characteristics of parental cells. Exosomes are widely present in various body fluids and can non-invasively, conveniently and real-timely extracted, with the potential to become a marker for early tumor diagnosis. Previous studies have shown that compared with traditional diagnostic methods, exosomes showed higher sensitivity and specificity in the early diagnosis of various cancers. This article reviews the research progress of exosomes in the early diagnosis of pancreatic cancer.
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In recent years, with the in-depth study of PD-1 and PD-L1 and the development of immunotherapy, the first problem is how to screen the beneficiaries. Recent clinical studies have shown that the expression level of PD-L1 in circulating tumor cells (CTC) can be used as a potential biomarker to play a guiding role in immunotherapy of malignant tumors. This article reviews the latest clinical research progress on the expression of PD-L1 in circulating tumor cells in various solid tumors.
ABSTRACT
Urine cell-free DNA (ucfDNA) contains DNA fragments released from the lysis of cells in the urinary system, and circulating cell-free DNA (ccfDNA) can also enter the urine after glomerular filtration, and the mutation information carried by tumor DNA contained in ucfDNA and ccfDNA is consistent. Therefore, as a biomarker for molecular diagnosis of urological and non-urinary tumors, ucfDNA, has become a research hotspot in the field of liquid biopsy in recent years. UcfDNA has potential application value in individualized treatment, early diagnosis, dynamic monitoring of therapeutic efficacy, and prognosis assessment, etc. However, in order to realize the clinical application of urine ucfDNA, the extraction and accurate detection of ucfDNA still need to be solved.
ABSTRACT
O carcinoma de células renais (CCR) é o sétimo tipo de câncer mais comum no ocidente e vêm apresentando um aumento em sua prevalência. A classificação histológica dos CCRs é a abordagem mais utilizada para determinar o subtipo da doença, bem como prognosticar o paciente. Cerca de 70-80% dos CCRs é do subtipo células claras (ccRCC), o qual representa o subtipo mais prevalente e agressivo da doença. A escolha do tratamento difere para cada paciente, sendo a ressecção cirúrgica a terapia mais efetiva nos casos de doença localizada. Apesar de ser um tratamento já estabelecido, estudos mostram uma certa heterogeneidade entre massas renais detectadas, onde cerca de 20% apresentam um perfil benigno, 60% são considerados tumores indolentes, sugerindo desta forma que, entender de forma mais detalhada este tumor pode auxiliar na escolha de um tratamento mais direcionado para o paciente. Sendo assim, o presente trabalho buscou selecionar genes potencialmente alterados em CCR com o intuito de customizar um painel multigênico capaz de identificar variantes somáticas, específicas do tumor, e avaliar as variantes específicas do tumor de forma personalizada em amostras de ctDNA (DNA tumoral circulante) extraídas de plasma e dos dois componentes da urina (sedimento e sobrenadante) coletados no momento da cirurgia (baseline). Neste contexto, dentro de nossa proposta, construímos um painel com 28 genes associados com CCR e sequenciamos 89 casos de tumores renais, juntamente com as amostras de leucócitos. Identificamos que dentre os tumores analisados, 59 apresentavam pelo menos uma variante somática, ou seja, o painel customizado apresentou uma sensibilidade para identificar variantes somáticas em 66% dos casos. Com relação aos 45 tumores classificados como ccRCC em 38 casos identificamos pelo menos uma marca tumoral, ou seja, nosso painel foi capaz de detectar variantes somáticas específicas do tumor em 84,4% desses casos. Um total de 105 variantes somáticas foram identificadas, e os genes mais frequentemente mutados nessa coorte de pacientes foram os genes VHL, PBRM1, BAP1, SETD2. Dos 59 casos em que identificamos variante somática, 44 casos foram avaliados as amostras baseline de plasma e 29 casos de urina (sobrenadante e sedimento), e encontramos pelo menos uma marca tumoral em um dos fluidos corpóreos em 11 pacientes, 6 em amostras de plasma e 6 amostras de urina. Através do desenvolvimento deste estudo, confirmamos que o subtipo ccRCC é o CCR mais bem caracterizado genomicamente e que é importante continuar a investigação genômica principalmente nos subtipos não ccRCC. Além disso o estudo demonstra a viabilidade de utilizar biópsia líquida ctDNA tanto no plasma quanto na urina para fins de diagnóstico e prognóstico.
Renal cell carcinoma (RCC) is the seventh most common type of cancer in the West and its prevalence is increasing. The histological classification of RCCs is the most used approach to determine the disease subtype as well as the patient's prognosis. About 70% of RCCs are of the clear cell Renal Cell Carcinoma subtype (ccRCC), which represents the most prevalent and aggressive subtype of the disease. The choice of treatment is different for each patient. Resection is one of the most effective therapies in cases of localized disease. Despite being an established treatment, studies show a certain heterogeneous profile studied. In this profile, up to 20% even present a benign treatment, helping the indolent, thus suggesting that understanding this tumor in detail can help to choose a more targeted treatment for the patient. Therefore, the present work aimed to select potentially altered genes in CCR in order to customize a multigene panel capable of identifying somatic, tumor-specific variants, and to evaluate the tumor-specific variants in a personalized way in ctDNA (circulating tumor DNA) samples extracted from plasma and from two components of urine (sediment and supernatant) collected at the time of surgery (baseline). In this context, within our proposal, we built a panel with 28 genes associated with CCR and sequenced 89 cases of renal tumors, together with leukocyte samples. We identified that among the analyzed tumors, 59 had at least one somatic variant, that is, the customized panel showed sensitivity to identify somatic variants in 66% of cases. Of the 45 classified as ccRCC in 38 cases we identified at least one tumor marker, that is, our panel was able to detect tumor-specific somatic variants in 84.4%. A total of 105 somatic variants were identified, and the genes most frequently mutated in this cohort of patients were the VHL, PBRM1, BAP1, SETD2 genes. Among 59 cases in which we identified somatic variant, 44 cases were evaluated in baseline plasma samples and 29 cases in urine (supernatant and sediment), and we found at least one tumor mark in one of the body fluids in 11 patients, 6 in plasma samples and 6 urine samples. Through the development of this study, we confirm that the ccRCC subtype is the best genomically characterized CCR and that it is important to continue genomic investigation, especially in the non-ccRCC subtypes. Furthermore, the study demonstrates the feasibility of using ctDNA liquid biopsy in both plasma and urine for diagnostic and prognostic purposes.
Subject(s)
Humans , Male , Female , Circulating Tumor DNA , Liquid Biopsy , Kidney Neoplasms , Carcinoma, Renal CellABSTRACT
ABSTRACT Objective: To evaluate sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of preoperative joint aspiration (PJA) and periarticular tissue percutaneous biopsy (PTPB), as well as their combination, in the diagnosis of infection after total hip arthroplasty. Methods: This cross-sectional study (Level of Evidence II) was conducted with prospective data on 29 patients submitted to PJA with PTPB at the National Institute of Orthopedics and Traumatology from September 2015 to January 2016. Specimens obtained during the procedures underwent microbiological analyses, and the results were compared with those obtained in subsequent revision arthroplasty surgeries. Results: PJA, PTPB, and their combination reached values of 78%, 73%, 89% for sensitivity, respectively; 72%, 90%, 94% for specificity; and 76%, 80%, 90% for accuracy. Conclusions: PJA combined with PTPB was sensitive, specific, and effective in diagnosing periprosthetic hip infection. Level of Evidence II, Prospective Cross-Sectional Study
RESUMO Objetivo: Avaliar a sensibilidade, especificidade, acurácia, valor preditivo positivo e valor preditivo negativo dos métodos diagnósticos aspirado articular pré-operatório (AAPO), biópsia percutânea de tecidos periarticulares (BPTP) e ambos associados na infecção pós-artroplastia total de quadril (IPATQ). Métodos: Trata-se de um estudo transversal (Nível de Evidência II) com coleta prospectiva de dados obtidos de 29 pacientes submetidos a AAPO com BPTP no Instituto Nacional de Ortopedia e Traumatologia durante o período de setembro de 2015 à janeiro de 2016. Foram comparados os resultados das análises microbiológicas dos espécimes obtidos por meio da BPTP e do AAPO com os obtidos intraoperatoriamente nas cirurgias subsequentes de revisão das artroplastias. Resultados: Encontramos uma sensibilidade da AAPO, BPTP e ambos, respectivamente de 78%, 73%, 89%, uma especificidade de 72%, 90%, 94% e uma acurácia de 76%, 80%, 90%. Conclusões: O procedimento de AAPO com BPTP para diagnóstico de infecção periprotética de quadril é sensível, específico e eficaz. Nível de Evidência II, Estudo Transversal Prospectivo.
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Lung cancer is the malignancy with the highest mortality rate worldwide. Malignant pleural effusion (MPE) caused by advanced lung cancer severely affects the quality of life and prognosis of patients. Tumor-associated genetic testing is the basis for making precise treatment decisions. There are some risks of tissue biopsy, and it is difficult to sample repeatedly. Due to its non-invasive and can reflect the full profile of tumor gene characteristics, liquid biopsy is increasingly used in the diagnosis and treatment of lung cancer. Because of the extremely low DNA level of circulating tumor, the sensitivity and specificity of liquid biopsy based on blood samples are limited. Tumor cells is enriched in MPE. The detection of cell-free DNA, extracellular vesicles and microRNA in MPE will be helpful to the diagnose, treatment and assess prognosis of patients with lung cancer. This review aims to discuss the research progress of liquid biopsy based on MPE in the diagnosis and treatment of lung cancer patients. .
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Microdialysis is a novel technique for rapid and continuous sampling of body fluid in the extracellular space, especially for some hard-to-obtain samples, e.g. cerebrospinal fluid, interstitial fluid. Microfluidic technology plays a significant role in body fluid analysis because of its miniaturization, high-throughput, and automation, offering a feasible method for rapid and low-cost biochemical analysis. In clinical practice, body fluid analysis is often required to be fast and/or capable of long-termly monitoring certain biomarkers. However, current technologies are insufficient to meet this requirement. The combination of microdialysis and microfluidic technologies could provide a new perspective to solve this problem.
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Objective:To verify the performance of the next-generation sequencing (NGS) platform and evaluate the application of NGS, droplet digital PCR (ddPCR) and super amplification refractory mutation system (super-ARMS) in the detection of circulating free DNA (cfDNA) mutations in patients with non-small-cell lung cancer (NSCLC).Methods:A total of 75 patients with NSCLC in the respiratory department of Zhongshan Hospital Affiliated to Fudan University were enrolled. The standards, cfDNA from 25 patients with newly diagnosed and untreated NSCLC, and self-made mixed samples mixed with hemoglobin (1 000 mg /dl), bilirubin (500 mg/l), fat emulsion (2%), enterococcus gDNA and Escherichia coli gDNA were used to verify the blank limit, analytical sensitivity, precision, accuracy and specificity of NGS platform. The cfDNA mutations of 75 NSCLC patients were detected by ddPCR and NGS, and the mutation positive rates of the two platforms were compared. The linear relationship between the two platforms was compared by Pearson correlation test. 12 patients were selected by simple random sampling for the detection of plasma super-ARMS platform. The performance of three platforms in the detection of plasma cfDNA mutation in patients with NSCLC was compared.Results:The blank limit of NGS platform was set to 0.00%, the analytical sensitivity was 0.2%, the intra-assay precision and inter-assay precision were 100%. The test results were not affected by endogenous hemoglobin, bilirubin or fat emulsion in plasma or exogenous DNA interference, and the analysis specificity was good. The mutation positive rates of plasma cfDNA in 75 NSCLC patients detected by ddPCR and NGS were 61.33% and 60.00%, respectively. The complete coincidence rate was 89.33%, which suggests there was a positive correlation between the mutation abundance of NGS and ddPCR ( r=0.984, P=0.001). Among the plasma of 12 NSCLC patients, the results of NGS, ddPCR and super-ARMS were completely consistent in 7 cases, including 2 wild-types and 5 mutants. Conclusion:The NGS platform was verified to be useful for cfDNA mutation detection in patients with NSCLC. The ddPCR, NGS and super-ARMS have their own advantages in detecting cfDNA mutations in patients with NSCLC.
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With the development of precision medicine and individualized treatment, tissue biopsy in cancer patients diagnosis and therapy has been broadly used. However, because it’s hard to collect enough samples for biliary tract tumors, liquid biopsy was broadly applied for the diagnosis. In liquid biopsy, circulating tumor cells, circulating tumor DNA, and tumor-derived exosomes carrying tumor-specific information are released from tumor tissue into blood, bile, and other body fluids, which makes tumor biopsy samples easily to be obtained in a non-invasive way. At the same time, through a series of morphological and molecular measurements as well as genetic characterization, liquid biopsy can be used to look for the new early diagnostic markers, and therapeutic targets, monitoring progression and prognosis of diseases. This article outlined the current technology used to detect circulating tumor cells, circulating tumor DNA, and tumor-derived exosomes, and summarizes the latest advances in the clinical application of liquid biopsy in biliary tract cancers.