Biomarkers For Diagnosis Of Cancer Research Articles

Imaging of cancer lipid metabolism in response to therapy.

Lipids represent a diverse array of molecules essential to the cell's structure, defense, energy, and communication. Lipid metabolism can often become dysregulated during tumor development. During cancer therapy, targeted inhibition of cell proliferation can likewise cause widespread and drastic changes in lipid composition. Molecular imaging techniques have been developed to monitor altered lipid profiles as a biomarker for cancer diagnosis and treatment response. For decades, MRS has been the dominant non-invasive technique for studying lipid metabolite levels. Recent insights into the oncogenic transformations driving changes in lipid metabolism have revealed new mechanisms and signaling molecules that can be exploited using optical imaging, mass spectrometry imaging, and positron emission tomography. These novel imaging modalities have provided researchers with a diverse toolbox to examine changes in lipids in response to a wide array of anticancer strategies including chemotherapy, radiation therapy, signal transduction inhibitors, gene therapy, immunotherapy, or a combination of these strategies. The understanding of lipid metabolism in response to cancer therapy continues to evolve as each therapeutic method emerges, and this review seeks to summarize the current field and areas of unmet needs.

Applying machine learning strategy for microsatellite status detection in plasma sample type.

e14219 Background: Microsatellite(MS) status is an important biomarker in cancer diagnosis . Most of available detection algorithms were based on figuring out number of validated allele types from control and cases, then determine the MS status by identify the difference. That would be suitable for tissue like samples due to their clear and sufficient tumor nucleic acid content. But for liquid biopsy such as plasma, lower ctDNA concentration and higher background ratio induced from laboratory and sequencing procedure make it necessary to develop novo method for plasma MS status detection. Methods: We developed an machine learning based approach to detect the MS status by using NGS sequencing data from plasma sample. 98 blood cell , 12 tumor tissue samples with PCR confirmed MSS status and 87 plasma samples from 134 patients were used to build normal baseline, and check the sequencing stability and population polymorphism of 207 candidate SSR locus in our panel. 97 locus then passed and were chosen as original biomarkers for model construction. For each coming sample, the allele probability distribution were obtained for each locus. Followed by calculating the Kullback–Leibler Divergence (KLD) value between target and baseline samples for each locus, the KLD value was used as input for feature selection and machine learning model fitting. Finally a leave one out strategy was used for model performance evaluation. Results: We obtained 17 most relevant SSR locus with suitable for MS status analysis of plasma sample. By using a SVM model fitted with 49 real patients sample data (21 MSI and 28 MSS) , The MS status prediction of plasma sample was of high sensitivity and specificity which were 90.47% and 96.42% respectively. Conclusions: Our results suggest that our MSI calculation model by using KLD value and SVM method is appropriate for the plasma sample. Further large-scale prospective studies are needed to validate our model.

Paralogous HOX13 Genes in Human Cancers.

Hox genes (HOX in humans), an evolutionary preserved gene family, are key determinants of embryonic development and cell memory gene program. Hox genes are organized in four clusters on four chromosomal loci aligned in 13 paralogous groups based on sequence homology (Hox gene network). During development Hox genes are transcribed, according to the rule of “spatio-temporal collinearity”, with early regulators of anterior body regions located at the 3’ end of each Hox cluster and the later regulators of posterior body regions placed at the distal 5’ end. The onset of 3’ Hox gene activation is determined by Wingless-type MMTV integration site family (Wnt) signaling, whereas 5’ Hox activation is due to paralogous group 13 genes, which act as posterior-inhibitors of more anterior Hox proteins (posterior prevalence). Deregulation of HOX genes is associated with developmental abnormalities and different human diseases. Paralogous HOX13 genes (HOX A13, HOX B13, HOX C13 and HOX D13) also play a relevant role in tumor development and progression. In this review, we will discuss the role of paralogous HOX13 genes regarding their regulatory mechanisms during carcinogenesis and tumor progression and their use as biomarkers for cancer diagnosis and treatment.

Immunoprofiling of Breast Cancer Antigens Using Antibodies Derived from Local Lymph Nodes.

Tumor antigens are responsible for initiating an immune response in cancer patients, and their identification may provide new biomarkers for cancer diagnosis and targets for immunotherapy. The general use of serum antibodies to identify tumor antigens has several drawbacks, including dilution, complex formation, and background reactivity. In this study, antibodies were generated from antibody-secreting cells (ASC) present in tumor-draining lymph nodes of 20 breast cancer patients (ASC-probes) and were used to screen breast cancer cell lines and protein microarrays. Half of the ASC-probes reacted strongly against extracts of the MCF-7 breast cancer cell line, but each with a distinct antigen recognition profile. Three of the positive ASC-probes reacted differentially with recombinant antigens on a microarray containing cancer-related proteins. The results of this study show that lymph node-derived ASC-probes provide a highly specific source of tumor-specific antibodies. Each breast cancer patient reacts with a different antibody profile which indicates that targeted immunotherapies may need to be personalized for individual patients. Focused microarrays in combination with ASC-probes may be useful in providing immune profiles and identifying tumor antigens of individual cancer patients.

Circulating miRNA-21 and miRNA-23a Expression Signature as Potential Biomarkers for Early Detection of Non-Small-Cell Lung Cancer.

Lung Cancer (LC) is a major cancer killer worldwide, and 5-yr survival is extremely poor (≤15%), accentuating the need for more effective diagnostic and therapeutic strategies. Studies have shown cell-free microRNAs (miRNAs) circulating in the serum and plasma with specific expression in cancer, indicating the potential of using miRNAs as biomarkers for cancer diagnosis and therapy. This study aimed to identify differentially-expressed two miRNAs in the plasma of Non-Small Cell Lung Cancer (NSCLC) patients that might be a clinically useful tool for lung cancer early detection. miRNA-21 is one of the most abundant oncomirs. miRNA-23a functions as an oncogene in several human cancers, however, its clinical value has not been investigated in NSCLC. A case-control study was conducted in Assiut University Hospital, Egypt, from 2017 to 2018. Plasma samples were obtained from 45 NSCLC patients. The expression level of miR-21 and miRNA-23a was detected by qRT-PCR and compared to 40 healthy control subjects. The relation between both miRNAs and clinicopathological parameters was evaluated. The expression level of miR-21 and miRNA-23a was significantly up-regulated (36.9 ± 18.7 vs. 1.12 ± 0.84 and 24.7 ± 19.09 vs. 1.16 ± 0.45) in NSCLC compared to matched controls (P<0.0001each). There was a significant difference in the level of plasma miRNA-21 and miRNA- 23a expression between the different grades of the disease (P = 0.032 and P = 0.001, respectively). The plasma miRNA-21 and miRNA-23a levels in the lung cancer patients with distant metastasis (n = 20) were significantly higher than those in the patients without metastasis (n = 25) (P<0.0001 each), the expression of miR-21 and miRNA-23a was significantly associated with tumor size (P = 0.001, P = 0.0001, respectively), but not significantly related to lymph node metastasis (P = 0.687 and 0.696, respectively). A positive correlation was observed between miRNA-21 and miRNA-23a (r = 0.784, P<0.01), There was no significant difference in the plasma miRNA-21 and miRNA-23a levels in the lung cancer patients with different histopathological types. miR-21 and miR-23a might play an oncogenic role in LC and is a poor prognostic factor. Switching off miRNA-21 and miRNA-23a may improve the treatment of LC. Our results must be verified by large-scale prospective studies with standardized methodology.

Ultrasensitive and Reversible Nanoplatform of Urinary Exosomes for Prostate Cancer Diagnosis.

Prostate cancer cell-derived exosomes in urine have been extensively studied recently and regarded as novel biomarkers for cancer diagnosis and prognosis, which presents wide prospects in clinical applications. Sensitive detection and specific capture methods are essential for exosomes analysis. Herein, a dual functional platform composed of superparamagnetic conjunctions and molecular beacons (SMC-MB) is reported. The SMC-MB platform is designed based on aptamer immunoaffinity with ultrasensitive detection efficiency and reversible isolation capacity, which, respectively, profit from nonenzymatic amplification methods and magnetic separation along with restriction cleavage. It is noteworthy that exosomes quantification was exactly amplified and transformed into single strand DNA detection. Correlated measurements evidence that the limit of detection of SMC-MB is as low as ∼100 particles/μL in urine, and a linear relationship meets between the logarithmic concentration of exosomes and fluorescence intensity of the molecular beacon. Furthermore, employing prostate specific membrane antigen (PSMA) aptamer, the platform adapted to detect and capture PMSA-positive exosomes from urine samples provides excellent diagnostic efficiency for prostate cancer (PCa). The expression of typical biomarkers of PCa, i.e., PSA and PCA3 mRNA, is significantly higher in PSMA-positive exosomes. Altogether, the platform and strategy described in this paper are promising in urinary exosomes analysis and prostate cancer detection.

Thymidine kinase 1 concentration in pleural effusion is a diagnostic marker and survival predictor for malignant pleural effusion.

ObjectiveThymidine kinase 1 (TK1) is a key enzyme in the pyrimidine salvage pathway. Increased TK1 concentration correlates with cell division. TK1 is an emerging biomarker in cancer diagnosis; however, its effectiveness in diagnosis and management for malignant pleural effusion (MPE) is unclear. We evaluated the diagnostic efficiency and prognostic value of pleural effusion TK1 (pTK1) concentration for MPE.MethodsFrom 2013 to 2017, 210 pleural effusion samples were collected from 160 patients diagnosed with MPE and 50 patients diagnosed with benign pleural effusion (BPE). TK1 concentrations in pleural effusion were measured by chemiluminescence dot blot assays. The median follow‐up was 12 months. We constructed a receiver‐operating characteristic (ROC) curve to find the optimal cutoff value for MPE diagnosis. The hazard ratios were estimated using a multivariable Cox proportional hazard model. A nomogram was drawn to illustrate the prognostic characteristics of MPE.ResultsThe TK1 concentration in pleural effusion was significantly higher in MPE than BPE (P < 0.001), and patients with MPE could be distinguished by an optimal cutoff value of 3.10 pmol/L with a sensitivity of 0.894 and a specificity of 0.800. The multivariate analysis suggested that pTK1 concentration was an independent predictor of survival in patients with MPE.ConclusionsThe diagnostic and prognostic prediction of MPE may be improved by measuring pTK1 concentration and utilizing a multivariate nomogram.

LnCAR: A Comprehensive Resource for lncRNAs from Cancer Arrays.

Long noncoding RNAs (lncRNA) have emerged as promising biomarkers in cancer diagnosis, treatment, and prognosis. Recent studies suggest that a large number of coding gene expression microarray probes could be reannotated as lncRNAs. Microarray, once the most cutting-edge high-throughput gene expression technology, has been used for thousands of cancer studies and has brought invaluable resources for studying the functions of lncRNA in cancer development. However, a comprehensive lncRNA resource based on microarray data is still lacking. Here, we present lnCAR (lncRNAs from cancer arrays), a comprehensive open resource for providing expression profiles and prognostic landscape of lncRNAs derived from reannotation of public microarray data. Currently, lnCAR contains 52,300 samples for differential expression analysis and 12,883 samples for survival analysis from 10 cancer types. lnCAR allows users to interactively explore any annotated or novel lncRNAs. We believe lnCAR will serve as a valuable resource for the community focused on lncRNA research in cancer. SIGNIFICANCE: lnCAR, a new interactive tool of reannotated public cancer-related microarray data, provides expression profiles and prognostic landscapes of lncRNAs across thousands of samples and multiple cancer types.

Noncoding Rnas Emerging as Novel Biomarkers in Pancreatic Cancer.

Noncoding RNAs play important regulatory roles in diverse biological processes and their misregulation might lead to different diseases, including cancer. Previous studies have reported the evolving role of miRNAs as new potential biomarkers in cancer diagnosis, prognosis, as well as predictive biomarkers of chemotherapy response or therapeutic targets. In this review, we outline the involvement of noncoding RNA in pancreatic cancer, providing an overview of known miRNAs in its diagnosis, prognosis and chemoresistance. In addition, we discuss the influence of non-coding RNAs in the metastatic behavior of pancreatic cancer, as well as the role of diet in epigenetic regulation of non-coding RNAs in cancer, which can, in turn, lead the development of new prevention's techniques or novel targets for cancer therapy.

Blood Circulating miRNAs as Cancer Biomarkers for Diagnosis and Surgical Treatment Response.

miRNAs can function as potential oncogenes or tumor suppressors. Altered expression of these molecules was correlated with the occurrence of many cancer diseases and therefore they are considered a molecular tool for non-invasive cancer diagnosis and prognosis. We searched for analyses concerning expression of blood circulating miRNA in cancer patients. The studies comprised of at least two miRNA expression measurements: before and after the surgical therapy were considered. We summarized latest reports on evaluation of the efficiency of anticancer therapy through observation of changes in expression of miRNA circulating in blood of patients treated with surgery alone. Twenty one research studies were identified. Thirty one different miRNAs were pointed out as potential both diagnostic and treatment response biomarkers since their deregulated expression before therapy returned to normal after receiving the treatment. Published data revealed a potential of circulating miRNA to become a tool giving a clinical follow up information on the efficiency of applied therapy. However, more observational studies on post-operative circulating miRNA expression changes are necessary.

Random and aligned electrospun PLGA nanofibers embedded in microfluidic chips for cancer cell isolation and integration with air foam technology for cell release

BackgroundCirculating tumor cells (CTCs) comprise the high metastatic potential population of cancer cells in the blood circulation of humans; they have become the established biomarkers for cancer diagnosis, individualized cancer therapy, and cancer development. Technologies for the isolation and recovery of CTCs can be powerful cancer diagnostic tools for liquid biopsies, allowing the identification of malignancies and guiding cancer treatments for precision medicine.MethodsWe have used an electrospinning process to prepare poly(lactic-co-glycolic acid) (PLGA) nanofibrous arrays in random or aligned orientations on glass slips. We then fabricated poly(methyl methacrylate) (PMMA)-based microfluidic chips embedding the PLGA nanofiber arrays and modified their surfaces through sequential coating with using biotin–(PEG)7–amine through EDC/NHS activation, streptavidin (SA), and biotinylated epithelial-cell adhesion-molecule antibody (biotin-anti-EpCAM) to achieve highly efficient CTC capture. When combined with an air foam technology that induced a high shear stress and, thereby, nondestructive release of the captured cells from the PLGA surfaces, the proposed device system operated with a high cell recovery rate.ResultsThe morphologies and average diameters of the electrospun PLGA nanofibers were characterized using scanning electron microscopy (SEM) and confocal Raman imaging. The surface chemistry of the PLGA nanofibers conjugated with the biotin–(PEG)7–amine was confirmed through time-of-flight secondary ion mass spectrometry (ToF–SIMS) imaging. The chip system was studied for the effects of the surface modification density of biotin–(PEG)7–amine, the flow rates, and the diameters of the PLGA nanofibers on the capture efficiency of EpCAM-positive HCT116 cells from the spiked liquid samples. To assess their CTC capture efficiencies in whole blood samples, the aligned and random PLGA nanofiber arrays were tested for their abilities to capture HCT116 cells, providing cancer cell capture efficiencies of 66 and 80%, respectively. With the continuous injection of air foam into the microfluidic devices, the cell release efficiency on the aligned PLGA fibers was 74% (recovery rate: 49%), while it was 90% (recovery rate: 73%) on the random PLGA fibers, from tests of 200 spiked cells in 2 mL of whole blood from healthy individuals. Our study suggests that integrated PMMA microfluidic chips embedding random PLGA nanofiber arrays may be suitable devices for the efficient capture and recovery of CTCs from whole blood samples.

The enigmatic role of matrix metalloproteinases in epithelial-to-mesenchymal transition of oral squamous cell carcinoma: Implications and nutraceutical aspects.

The most prevalent malignancy in the oral cavity is represented by oral squamous cell carcinoma, an aggressive disease mostly detected in low-income communities. This neoplasia is mostly diffused in older men particularly exposed to risk factors such as tobacco, alcohol, and a diet rich in fatty foods and poor in vegetables.In oral squamous cell carcinoma, a wide range of matrix-cleaving proteinases are involved in extracellular matrix remodeling of cancer microenvironment. In particular, matrix metalloproteinases (MMPs) represent the major and most investigated protagonists. Owing to their strong involvement in malignant pathologies, MMPs are considered the most promising new biomarkers in cancer diagnosis and prognosis. The interest in studying MMPs in oral cancer biology is also owing to their prominent role in epithelial-to-mesenchymal transition (EMT). EMT is an intricate process involving different complex pathways. EMT-related proteins are attractive diagnostic biomarkers that characterize the activation of biological events that promote cancer's aggressive expansion. Different antioncogenic natural compounds have been investigated to counteract oral carcinogenesis, with the scope of obtaining better clinical results and lower morbidity. In particular, we describe the role of different nutraceuticals used for the regulation of MMP-related invasion and proliferation of oral cancer cells.

Clinical significance of exosomes as potential biomarkers in cancer

BACKGROUNDExosomes are microvesicles, measuring 30-100 nm in diameter. They are widely distributed in body fluids, including blood, bile, urine and saliva. Cancer-derived exosomes carry a wide variety of DNA, RNA, proteins and lipids, and may serve as novel biomarkers in cancer.AIMTo summarize the performance of exosomal biomarkers in cancer diagnosis and prognosis.METHODSRelevant publications in the literature were identified by search of the “PubMed” database up to September 11, 2018. The quality of the included studies was assessed by QUADAS-2 and REMARK. For assessment of diagnostic biomarkers, 47 biomarkers and 2240 patients from 30 studies were included.RESULTSOur results suggested that these exosomal biomarkers had excellent diagnostic ability in various types of cancer, with good sensitivity and specificity. For assessment of prognostic markers, 50 biomarkers and 4797 patients from 42 studies were included. We observed that exosomal biomarkers had prognostic values in overall survival, disease-free survival and recurrence-free survival.CONCLUSIONExosomes can function as potential biomarkers in cancer diagnosis and prognosis.

Clinicopathological significance of RCAN2 production in gastric carcinoma.

Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. Genes expressed only in cancer tissue may be useful biomarkers for cancer diagnosis and therapeutics. The aims of the present study were to analyse regulator of calcineurin 2 (RCAN2) in a large number of GCs, and to investigate how these expression patterns correlate with clinicopathological parameters and various markers. An immunohistochemical analysis of RCAN2 in 207 GC tissue samples showed that 110 (53%) GCs were positive for RCAN2. RCAN2-positive GCs were more advanced in terms of TNM classification and tumour stage than RCAN2-negative GCs. Furthermore, RCAN2 was an independent prognostic classifier for GC patients. The cell growth and invasiveness of RCAN2 small interfering RNA (siRNA)-transfected GC cell lines were less than those of the negative control siRNA-transfected cell lines, whereas those of RCAN2-transfected cells were significantly increased as compared with those of empty vector-transfected cells. RCAN2 siRNA inhibits the phosphorylation of AKT and p44/p42 (ERK1/2). RCAN2 was colocalised with EGFR, nuclear β-catenin, MMP7, laminin-γ2, VEGF-A, and VEGF-C. These results suggest that RCAN2 is involved in tumour progression and is an independent prognostic classifier in patients with GC.

The value of methylated circulating tumor DNA as biomarkers in cancer diagnosis and prognosis

Circulating tumor DNA (ctDNA) in the blood of cancer patients provides an opportunity for non-invasive sampling of tumor DNA. This liquid biopsy allows for detection of copy number variations, tumor-specific mutations, epigenetic changes, and can be used to guide and improve treatment throughout real-time tracking the course of tumor disease. Aberrant methylation of specific gene regions can be a very consistent feature of cancer, in contrast to mutations, which makes ctDNA methylation amenable to the design of widely clinical applications in early diagnosis, monitoring disease status, predicting treatment response and predicting prognosis. Therefore, ctDNA methylation detection is considered as one of the most valuable methods for cancer diagnosis and risk assessment. Key words: Neoplasms; Circulating tumor DNA; DNA methylation; Prognosis

T7 exonuclease-assisted and target-triggered cascade dual recycling signal amplification strategy for the sensitive and specific detection of adenosine

Adenosine is closely related to the development of cancer, and it can be regarded as a biomarker for cancer diagnosis and therapy. Here, a T7 exonuclease (T7 Exo)-assisted and target-triggered cascade dual recycling signal amplification strategy was developed for the sensitive and specific detection of adenosine. In this strategy, a capture strand (Cap)-inhibit strand (Inh) duplex and a DNA hairpin with intact G-quadruplex sequence are designed. In the presence of adenosine, Cap binds with adenosine specifically to form Cap-adenosine complex with recessed 5′-hydroxyl termini, causing the release of Inh. Under the action of T7 Exo, the adenosine is released from Cap-adenosine complex. Then the released adenosine interacts with the next Cap-Inh duplex to promote the release of a new Inh and the recycle I is completed. After that, the released Inh hybridizes with hairpin to form Inh-hairpin duplex with blunt 5′ -hydroxyl termini. Under the same action of T7 Exo, the Inh gets released and a G-quadruplex sequence is obtained. Subsequently, the released Inh continues opening hairpin and the recycle II is accomplished. Finally, plenty of G-quadruplex sequences are generated and then interact with N-methyl-mesoporphyrin IX (NMM) to obtain enhanced fluorescence signal. The limit of detection (LOD) of the proposed strategy is estimated to be 9.8 × 10−7 mol L−1, and the linear range of the strategy is from 5.0 × 10−6 mol L−1 to 7.0 × 10−4 mol L−1. Besides, the proposed strategy is capable of distinguishing adenosine from its analogues. This strategy holds promise in adenosine related biomedical research, clinical diagnosis and disease treatment.

Epigenetic Alternations of MicroRNAs and DNA Methylation Contribute to Liver Metastasis of Colorectal Cancer

Liver metastasis is a major cause of mortality in colorectal cancer (CRC). Epigenetic alternations could serve as biomarkers for cancer diagnosis and prognosis. In this study, we analyzed microarray data in order to identify core genes and pathways which contribute to liver metastasis in CRC under epigenetic regulations. Data of miRNAs (GSE35834, GSE81582), DNA methylation (GSE90709, GSE77955), and mRNA microarrays (GSE68468, GSE81558) were downloaded from GEO database. Differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs), and differentially methylated genes (DMGs) were obtained by GEO2R. The target genes of DEMs were predicted by miRWalk. Functional and enrichment analyses were conducted by DAVID database. Protein-protein interaction (PPI) network was constructed in STRING and visualized using Cytoscape. In liver metastasis, miR-143-3p, miR-10b-5p, miR-21-5p, and miR-518f-5p were down-regulated, while miR-122-5p, miR-885-5p, miR-210-3p, miR-130b-5p, miR-1275, miR-139-5p, miR-139-3p, and miR-1290 were up-regulated compared with primary CRC. DEGs targeted by altered miRNAs were enriched in pathways including complement, PPAR signaling, ECM-receptor interaction, spliceosome, and focal adhesion. In addition, aberrant DNA methylation-regulated genes showed enrichment in pathways of amino acid metabolism, calcium signaling, TGF-beta signaling, cell cycle, spliceosome, and Wnt signaling. Our study identified a series of differentially expressed genes which are associated with epigenetic alternations of miRNAs and DNA methylation in colorectal liver metastasis. Up-regulated genes of SLC10A1, MAPT, SHANK2, PTH1R, and C2, as well as down-regulated genes of CAB39, CFLAR, CTSC, THBS1, and TRAPPC3 were associated with both miRNA and DNA methylation, which might become promising biomarker of colorectal liver metastasis in future.

Glycan-based biomarkers for diagnosis of cancers and other diseases: Past, present, and future.

Glycans are essential biomolecules in regulating human physiology and pathology ranging from signal transduction to microbial infections. Developing complex human diseases, such as cancer, diabetes, and cardiovascular diseases, are a combination of genetic and environmental factors. Genetics dominates embryonic development and the passing of genes to the next generation whereas the information in glycans reflects the impact of internal and external environmental factors, such as diseases, lifestyle, and social factors, on a person's health and disease. The reason behind this is that glycans are not directly encoded in a genetic template. Instead, they are assembled dynamically by hundreds of enzymes organized in more than 10 complex biosynthetic pathways. Any environmental changes affecting enzymatic activities or the availability of high-energy monosaccharide donors in a specific location will disturb the final structure of glycans. The glycan structure-dependent biological activities subsequently enable or disable gene expressions, which partially explain that it is difficult to pinpoint specific genetic defects to aging-associated diseases. Glycan-based biomarkers are currently used for diagnosis of diabetes, cancers, and other complex diseases. We will recapitulate the discovery of glucose, glycated proteins, glycan-, and glycoprotein-based biomarkers followed by summarizing clinically used glycan/glycoprotein-based biomarkers. The potential serum/plasma-derived N- and O-linked glycans as biomarkers will also be discussed.

Emerging Roles of p53 Related lncRNAs in Cancer Progression: A Systematic Review.

p53 is the major mediator of the tumor suppressor response. It participates in apoptosis and senescence and can respond to DNA damage. As a crucial sequence-specific transcription factor, p53 regulates the expression of many genes, such as small noncoding RNAs (ncRNAs), microRNAs, and long ncRNAs (lncRNAs). Given the emergence of novel and high-throughput sequencing technologies, many lncRNAs have been discovered. LncRNAs may function as vital gene regulators in a variety of biological processes through extensive mechanisms. Recently, lncRNAs have been demonstrated to be associated with the p53 regulatory pathway. In this review, we discuss the current and fast growing knowledge about the influence of lncRNAs to the p53 signaling pathway, the different mechanisms by which they affect gene expression in cancer. Our findings show that p53-associated lncRNAs may be used as biomarkers for cancer diagnosis or targets for disease therapy.

Ultrasensitive detection of lung cancer-associated miRNAs by multiple primer-mediated rolling circle amplification coupled with a graphene oxide fluorescence-based (MPRCA-GO) sensor.

MicroRNAs (miRNAs) play important roles in gene regulation and have been reported as biomarkers in cancer diagnosis. Herein, we develop an isothermal miRNA detection platform based on the highly efficient, multiple primer-mediated rolling circle amplification method coupled with a graphene oxide-based fluorescence (MPRCA-GO) assay, using lung cancer-associated miRNAs (miR-21 and miR-210) and a reference miRNA (miR-16) as model targets. The combination of the designed ssDNA probe and T4 RNA ligase (T4 Rnl2) used in the MPRCA-GO assay allowed for single-base mismatch discrimination. In addition, the superfluorescence quenching ability of GO allowed for rapid fluorescence detection. The developed platform had a limit of detection as low as 0.87 fM and could detect target miRNAs in cancer cell lines and human serums. Therefore, the MPRCA-GO sensor has the potential for single nucleotide polymorphism (SNP) analysis and applications in clinical diagnostics.