Search

Small nucleolar RNA host gene 10 (SNHG10) is a newly recognized long non-coding RNA (lncRNA) with significant implications in cancer biology. Abnormal expression of SNHG10 has been observed in various solid tumors and hematological malignancies. Research conducted in vivo and in vitro has revealed that SNHG10 plays a pivotal role in numerous biological processes, including cell proliferation, apoptosis, invasion and migration, drug resistance, energy metabolism, immune evasion, as well as tumor growth and metastasis. SNHG10 regulates tumor development through several mechanisms, such as competing with microRNA (miRNA) for binding sites, modulating various signaling pathways, influencing transcriptional activity, and affecting epigenetic regulation. The diverse biological functions and intricate mechanisms of SNHG10 highlight its considerable clinical relevance, positioning it as a potential pan-cancer biomarker and therapeutic target. This review aims to summarize the role of SNHG10 in tumorigenesis and cancer progression, clarify the molecular mechanisms at play, and explore its clinical significance in cancer diagnosis and prognosis prediction, along with its therapeutic potential. • SNHG10 is abnormally expressed in various solid tumors and hematological malignancies. • SNHG10 is involved in a series of crucial biological processes related to tumor development. • SNHG10 regulates tumor progression through multiple mechanisms. • SNHG10 holds promise as a biomarker for cancer diagnosis and prognosis prediction. • SNHG10 presents as a promising target for cancer therapeutics. [ABSTRACT FROM AUTHOR]

Early diagnosis and screening of tumor markers are essential for effective cancer treatment and improve the treatment efficiency and prognosis of tumor recurrence and metastasis. In this study, a split-ring resonator (SRR) circuit based on an interdigital electrode structure was developed and applied to microwave biosensors along with machine learning to detect extremely low concentrations of Carcinoembryonic Antigen (CEA). CEA was detected using a microwave sensor operating at a resonance frequency of 4.33 GHz. When the microwave sensor is exposed to CEA analytes, it generates a new frequency in the range of 1–2 GHz. The position and intensity of the newly generated frequency can be used to characterize and predict the concentration of the CEA solution. The proposed sensor exhibits excellent resonance linearity for various concentrations of CEA (R 2 = 0.999), as well as a very low detection limit (39 pg/mL) and high sensitivity (27.5 MHz/(ng/mL)). A machine learning approach was implemented to predict the CEA concentration in blood samples. The results showed close concurrence with the CEA concentration detected by the sensor. Western Blot (WB) was used to compare the CEA contents of four different cell types, and a biosensor was used for validation; the results of the two experiments showed good agreement. This is the first demonstration of the validation of biosensor reliability at the cellular level. The proposed concept exhibits outstanding detection performance with convenient and rapid tumor marker detection. Hence, it has important implications as an auxiliary diagnosis method for cancer. [ABSTRACT FROM AUTHOR]

Gynecological cancers that affect female reproductive tract, remain at the top of the global cancer burden list with high relapse rate and mortality. Notwithstanding development of several novel therapeutic interventions including poly-ADP-ribose polymerase inhibitors, this family of malignancies remain deadly. The human microbiome project demonstrated that dysbiosis of health resident microflora is associated with several pathologies including malignancies of the female reproductive tract and detailed characterization of species variation and host-microbe interaction could provide clues for identification of early diagnostic biomarker, preventive and therapeutic interventions. Emerging evidence suggests that several microbial signatures are significantly associated with gynecological cancers. An increased population of Proteobacteria and Firmicutes followed by significantly reduced Lactobacilli are associated with lethal epithelial ovarian cancer. Similarly, a constant association of elevated level of Atopobium vaginae, Porphyromonas somerae, Micrococci and Gardnerella vaginalis are observed in endometrial and cervical cancers. Moreover, human papilloma virus infection significantly augments colonization of pathogenic microbes including Sneathia sanguinegens , Anaerococcus tetradius , and Peptostreptococcus anaerobius and drives carcinoma of the cervix. Interestingly, microbial dysbiosis in female reproductive tract modulates expression of several microbial and immune-responsive genes such as TLR-4, TLR-5, TLR-6 and NOD-1. Therefore, stringent investigation into the microbial dysbiosis and its underlying mechanism could provide valuable cues for identification of early diagnostic biomarker, preventive and therapeutic interventions against rogue gynecological malignancies. • Gynecological malignancies top the global cancer burden chart. • Human microbial dysbiosis often drives gynecological malignancies. • Altered microbial signatures might act as early prognostic biomarkers. • Microbial dysbiosis is potential new therapeutic target in gynecological malignancy. [ABSTRACT FROM AUTHOR]

• We describe contemporary genomic testing in advanced non-small cell lung cancer. • We used the Flatiron Health electronic health record-based de-identified database. • Next-generation sequencing may help to avoid potentially missed targeted therapies. • Next-generation sequencing may improve testing for recently approved biomarkers. • Results support guideline-recommended next-generation sequencing in clinical care. According to 2018 United States and international lung cancer and pathology guidelines, testing of EGFR , ALK , ROS1 and BRAF genes is a minimum requirement to identify targeted therapy options in patients with advanced non-small cell lung cancer (aNSCLC). We describe real-world use and clinical features of next-generation sequencing (NGS) and other non-NGS testing technologies in these patients. Patients were from the Flatiron Health electronic health record-derived de-identified database and were newly diagnosed with non-squamous aNSCLC between 1 January 2018 and 30 June 2019. We describe occurrence and patterns of NGS- (including comprehensive genomic profiling [CGP]) and non-NGS-based genomic testing before the start of first-line therapy, unsuccessful genotyping (<4 genes tested) and incidence of potentially missed targeted therapy options (<4 genes tested with no positive results). Among 3050 patients, 2356 received any type of genomic testing (NGS: 1406 [59.7%]). Unsuccessful genotyping occurred in 13.2% and 52.2% of NGS- and non-NGS-tested patients, respectively. Among NGS-tested patients, 10.0% had a potentially missed targeted therapy option (CGP: 2.9%), compared with 40.2% in the non-NGS tested group. While all four guideline-recommended genes were tested in ≥ 92% of patients who had NGS testing, when only non-NGS testing was used, although EGFR and ALK had similarly high testing proportions, BRAF and ROS1 (56.1% and 83.7%, respectively) were examined less often. Our findings suggest that in aNSCLC clinical practice, NGS testing may help to avoid potentially missed targeted therapy options and improve testing uptake for recently approved biomarkers. Results therefore support the use of guideline-recommended broad-panel NGS testing in clinical practice. [ABSTRACT FROM AUTHOR]

Hepatoblastoma is the most common liver malignancy in children. In order to advance therapy against hepatoblastoma, novel immunologic targets and biomarkers are needed. Our purpose in this investigation is to examine hepatoblastoma transcriptomes for the expression of a class of genomic elements known as Human Endogenous Retrovirus (HERVs). HERVs are abundant in the human genome and are biologically active elements that have been associated with multiple malignancies and proposed as immunologic targets in a subset of tumors. A sub-family of HERVs, HERV-K(HML-2) (HERV-K), have been shown to be tightly regulated in fetal development, making investigation of these elements in pediatric tumors paramount. We first created a HERVK-FASTA file utilizing 91 previously described HML-2 proviruses. We then concatenated the file onto the GRCh38.95 cDNA library from Ensembl. We used this reference database to evaluate existing RNA-seq data from 10 hepatoblastoma tumors and 3 normal liver controls (GEO accession ID: GSE8977575). Quantification and differential proviral expression analysis between hepatoblastoma and normal liver controls was performed using the pseudo-alignment program Salmon and DESeq2, respectively. HERV-K mRNA was expressed in hepatoblastoma from multiple proviral loci. All expressed HERV-K proviral loci were upregulated in hepatoblastoma compared to normal liver controls. Five HERV-K proviruses (1q21.3, 3q27.2, 7q22.2, 12q24.33 and 17p13.1) were significantly differentially expressed (p-adjusted value < 0.05, | log2 fold change | > 1.5) across conditions. The provirus at 17p13.1 had an approximately 300-fold increased expression in hepatoblastoma as compared to normal liver. This was in part due to the near absence of HERV-K mRNA at the 17p13.1 locus in fully differentiated liver samples. Our investigation demonstrates that HERV-K is expressed from multiple loci in hepatoblastoma and that the expression is increased for several proviruses compared to normal liver controls. Our results suggest that HERV-K mRNA expression may be useful as a biomarker in hepatoblastoma, given the large differential expression profiles in hepatoblastoma, with very low mRNA levels in liver control samples. [ABSTRACT FROM AUTHOR]

Carcinoembryonic antigen (CEA) is a well-known cancer biomarker for the detection of several malignancies. The development of ultrasensitive CEA diagnostic tools is crucial for early detection and progression observation of tumors. Herein, a dual signal amplified sandwich-type electrochemical immunoassay was developed based on dual-labeled mesoporous silica nanospheres as a signal amplifier, combined with NiO@Au decorated graphene as a conductive layer for ultrasensitive and rapid determination of CEA. The dual-labeled mesoporous silica (DLMS) nanosphere, which was synthesized by entrapping Au nanorod (Au NR) and horseradish peroxidase (HRP) in the channels of amine-functionalized SBA-15 followed by subordinate antibody (Ab 2) conjugation which was denoted as Au NR@SBA-15/Ab 2 -HRP. The dual signal amplification from Au NR@SBA-15 and HRP enhanced the sensitivity of the proposed immunoassay. Consequently, the developed DLMS based immunosensor displayed ultra-low limits of detection of 5.25 fg/mL and a wide range of linearity (0.1–5 pg/mL), which was extended for CEA determination in real-time samples with improved recoveries of >98%. Therefore, this dual amplification prototype would cater to the clinical requirements for the ultrasensitive detection of CEA biomarkers. Schematic Representation of a NiO@Au Nanoparticle Decorated Graphene and Dual Labeled Mesoporous Silica (DLMS) Nanospheres Based Electrochemical Sensor for the Ultrasensitive Detection of Carcinoembryonic (CEA) Antigen in Real Time Samples. Image 1 • Ultrasensitive detection of CEA was achieved by the dual signal amplified electrochemical sensor. • The dual-labeled mesoporous silica nanospheres were used as a signal amplifier. • Rapid charge-carrier transport was realized from the interior to fixed biomolecules. • The limit of detection was 5.25 fg/mL with a wide linear range from 0.1 to 5 pg/mL. • The proposed sensor shows recoveries more than 98% in real-time human samples. [ABSTRACT FROM AUTHOR]

Abstract Background Serum-based tumor biomarkers are used to monitor cancer treatment, while clear guidance on the clinical usage is often lacking. We describe a graphical presentation to support diagnostic accuracy studies and clinical interpretation of longitudinal biomarker data. Methods A biomarker response characteristic (BReC) plot was designed. To allow demonstration of the BReC plot application, software was developed that supported 1) dynamic generation of BReC plots, and 2) diagnostic accuracy studies of biomarker response-based medical tests. The BReC plot application was demonstrated using serial carcinoembryonic antigen (CEA) and Cyfra 21.1 results from 216 patients with metastasized non-small cell lung cancer, treated with Nivolumab in routine clinical practice. Results The developed software supported the generation of BReC plots and diagnostic validation of biomarker response-based medical tests by generating the sensitivity, specificity and predictive values. Obtained BReC plots showed a clear relationship between clinical outcome and CEA and Cyfra 21.1 responses. Furthermore, using BReC plots, CEA and Cyfra 21.1 based medical tests were designed with a sensitivity for detection of treatment failure of 0.34 and 0.35 and a specificity of 0.96. Conclusions The BReC plot appears to support diagnostic validation studies and the interpretation of longitudinal biomarkers though further validation is warranted. Highlights • Clear guidance on the clinical usage of serum tumor biomarkers is often lacking. • Software was developed that supported BReC-plots and diagnostic accuracy studies. • The BReC plot application was demonstrated using 216 advanced lung cancer patients. • Obtained BReC-plots revealed relations between biomarker and clinical responses. • Medical tests could be designed that met pre-specified performance criteria. [ABSTRACT FROM AUTHOR]

Telomerase is a basic nuclear protein reverse transcriptase and responsible for the elongation of telomeres in cells. It has attracted a lot of attentions and acted as an important sally port for cancer diagnosis and clinical therapy. Hence, accurate and efficient determination of telomerase activity is significant. In recent years, numerous sensitive and accurate techniques have been developed for in vitro or in situ detection of telomerase activity. These methods were mainly dependent on three unique properties of elongated telomerase primer (TS primer): 1) Plenty of negative charges play important role to change interactions between biomolecules and signal probes; 2) G-rich sequences have excellent peroxidase-like catalytic activity; 3) They can be used for DNA hybridization or strand displacement reaction, which are beneficial to construct biosensors. In this review, we conclude and enumerate these advanced methods for telomerase activity detection in recent years. Development trends of telomerase detection are also prospected. [ABSTRACT FROM AUTHOR]

DNA has emerged as a promising biomaterial for assembling a variety of nanostructures based on its programmable base pairing. It also has other remarkable properties including stability, prominent biocompatibility, and can easily be modified with functional groups for further applications. In the past few decades, researchers have established various design rules and assembly technologies to improve the stability and complexity of DNA nanostructures. The detection of cancer-associated biomarkers has significant importance in identifying patients with different clinical stages and also in developing adaptive therapeutic strategies. Due to their unique advantages, DNA nanostructures can be designed to serve as universal units to form biosensors for the detection of tumor biomarkers. In this review, we first present a brief introduction of the development of structural DNA nanotechnology. Then we summarize recent strategies for DNA nanostructure-based optical, electrochemical and mass sensitive biosensors in cancer detection. Finally, we discuss the challenges and opportunities these technologies provide. [ABSTRACT FROM AUTHOR]

MicroRNA-21 (miRNA-21) is widely expressed in various organs and tissues of mammals, including the heart, lungs, brain, pancreas, small intestine, colon, breast, and kidneys, showing high sensitivity and specificity in the diagnosis of multiple types of tumors. It can serve as a new clinical early diagnosis and prognostic biomarker for tumors. This study proposes a self-powered bioplatform, which employs a biological cathode double signal amplification design to construct a high-performance enzyme biofuel cell for the ultra-sensitive detection of tumor biomarker miRNA-21. The biocathodic double signal mechanism involves the catalyzed hairpin self-assembly introduction signal I bilirubin oxidase and a tetrahedral DNA nanostructure that produces a double-helical DNA chain to adsorb signal II electron acceptor [Ru(NH 3) 6 ]3+. This approach not only improves the stability of the sensing system, but also synergistically enhances the open circuit voltage. The developed assay exhibits a wide linear range from 0.1 fM to 1000 pM, with a low detection limit of 0.04 fM (S/N = 3). This study provides a strategy for designing biosensors with improved sensitivity and potential application in medical diagnosis field. • A self-powered biosensor for detection of tumor biomarker is developed using biocathodic double signal amplification design. • CHA and tetrahedral DNA nanostructure can produce a long double-helical DNA chain to introduce signal- electron acceptor. • The developed assay not only improves the stability, but also greatly enhances the sensitivity and selectivity. [ABSTRACT FROM AUTHOR]

DNA point mutation in a BRAF proto-oncogene, V600E, is considered an important prognostic and predictive biomarker in various types of cancer, such as melanoma or colorectal cancer. We report here a novel electrochemical (EC) bioplatform for the analysis of BRAF V600E mutation coupled with rolling circle amplification (RCA) and locked nucleic acid (LNA) capture probes. A dual detection system was implemented, whereby two padlock probes complementary to either wild-type (wt) BRAF gene or DNA with V600E mutation (mut) led to amplification of wt or mut variant, respectively. Hybridization with specific LNA capture probes then increased the assay specificity, while EC detection provided rapid measurement times. The bioplatform was applied to analyze BRAF V600E mutation of cancer cells and tumor tissues from patients with melanoma or colorectal cancer. This is the first RCA-based EC bioplatform for BRAF analysis in a dual format without using PCR or sophisticated instrumentation. [Display omitted] • Dual electrochemical bioplatform for analysis of BRAF V600E mutation status. • Rolling circle amplification with LNA capture probes provided excellent selectivity. • Rapid measurement on screen-printed eight-electrode chips. • Successful application to cancer cells and tumor tissues from cancer patients. [ABSTRACT FROM AUTHOR]

[Display omitted] • The accurate sensing of tumor biomarkers based on biosensors is becoming one of the most promising strategies for cancer diagnostics. • Four types of biosensors including electrochemical, optical, piezoelectric, and mass spectrometric biosensors with the enhancement mechanisms via material are summarized. • The recent advances and limitations in material-enhanced biosensors for cancer biomarkers detection are reviewed. Cancer is a leading cause of death worldwide, the early diagnosis of which decides the patient's prognosis. The accurate sensing of tumor biomarkers is becoming one of the most promising strategies for cancer management. Advanced materials possess unique structures and tunable physicochemical properties, making them attractive for developing various sensing systems, including electrochemical, optical, piezoelectric, and mass spectrometry sensors. Herein, the enhancing mechanisms in various sensing techniques are summarized, regarding the advanced materials chosen. The real-case applications of the material-enhanced biosensors are reviewed, with special emphasis on cancer biomarkers detection. We anticipate that the advanced materials will bring far-reaching implications to clinical biosensing for academic and industrial use. [ABSTRACT FROM AUTHOR]

The diagnostic, monitoring and therapeutic options for cancers currently remain limited. These limitations represent a large threat to human health. Adaptive immunity, which is dependent on diverse repertoires of B cell receptors (BCRs) and T cell receptors (TCRs), plays a critical role in the anti-tumor immune response. Modulation and surveillance of adaptive immunity has become a powerful weapon to combat cancers. Recently, the high-throughput sequencing of immune repertoire (HTS-IR) technology, which provides a robust tool for deep sequencing repertoires of BCRs or TCRs, has been applied in the development of tumor biomarkers and immunotherapeutics for cancers. This review will first provide an overview of the advancement of HTS-IR technology at the population-cell and single-cell levels. It will then provide a current summary of the applications of HTS-IR technology in the diagnosis and monitoring of minimal residual disease (MRD), focusing on immune reconstitution after the treatment of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in B/T-cell malignancies, and the precise detection of tumor-infiltrating lymphocytes (TILs) in non-B/T-cell malignancies. Finally, current advances of HTS-IR technology in cancer immunotherapeutic applications, such as therapeutic antibodies, CAR-T cell based-adoptive immunotherapies, and neoantigen-specific TCR-T cell-based adoptive immunotherapies, will be introduced. [ABSTRACT FROM AUTHOR]

We report on the detection of an angiogenic molecule Vascular Endothelial Growth Factor (VEGF) in different biological matrices by means of a new integrated biosensing platform exploiting the properties of Bloch surface waves. The new platform takes advantage of a tandem configuration, in which both label-free and enhanced fluorescence detection are implemented. Specifically designed one dimensional photonic crystals were deposited directly on disposable and low cost plastic biochips. A direct sandwich immunoassay was used to detect VEGF in buffer, cell culture supernatant and human plasma at low concentration (ng/mL). The platform enabled the detection of VEGF in all three matrices with high resolution, fast turnaround time (30 min) and in close agreement with the results of enzyme linked immunosorbent assays. [ABSTRACT FROM AUTHOR]

Rapid and effective differentiation between normal and cancer cells is an important objective for the diagnosis, prognosis and theranosis of tumors. This short review highlights some of the most recent developments on the application of molecular bioimprinting in detection of cancer cells using antibody-based cancer cell recognition method. The particular emphasis of this review is on sample-to-answer devices and approaches that enable down-stream investigation of the properties of the cells. Given the speed, portability, sensitivity and selectivity achieved using molecular bioimprinting technology on cancer cell monitoring, these methods hold the promise of transformative change in clinical practice. [ABSTRACT FROM AUTHOR]

In this work, a new conductive hydrogel was prepared by a simple cross-linking coordination method using 1,3,5-benzenetricarboxylic acid as the ligand and Fe 3 + as the metal ion. The hydrogel film was formed on a glassy carbon electrode (GCE) by a drop coating method, which can dramatically facilitate the transport of electrons. A sensitive label-free electrochemical immunosensor was fabricated following electrodeposition of gold nanoparticles (AuNPs) on a hydrogel film and immobilization of an antibody. Neuron-specific enolase (NSE), a lung cancer biomarker, was used as the model analyte to be detected. The proposed immunosensor exhibited a wide linear detection range of 1 pg mL − 1 to 200 ng mL − 1 and a limit of detection of 0.26 pg mL − 1 (the ratio of signal to noise (S/N) = 3). Moreover, the detection of NSE in human serum samples showed satisfactory accuracy compared with the data determined by enzyme-linked immunosorbent assay (ELISA), indicating good analytical performance of the immunoassay. [ABSTRACT FROM AUTHOR]

In this work, a kind of novel redox-active species, metal-organic nanocomposites with uniform morphology and good conductivity, was synthesized by one-pot method using HAuCl 4 as oxidant and methylene blue as monomer. With excellent biocompatibility of Au, the immunosensing probe was fabricated by means of immobilization of antibody on the nanocomposites for the purpose of signal amplification. Meanwhile, graphene-Au modified electrode was used as the substrate. A new electrochemical immunosensing platform was designed and simply fabricated. With the use of α-fetoprotein (AFP) as a model analyte, good performance was obtained with a wide linear range from 1 pg mL −1 to 100 ng mL −1 , and low detection limit of 19.6 fg mL −1 . The assay results of clinical serum with this immunoassay were well consistent with those obtained from ELISA method. The present work suggested an electrochemical immunosensing platform for tumor biomarker. [ABSTRACT FROM AUTHOR]

In this study, we developed a multiplex immunoassay system that combines the suspension and planar microarray formats within a single layer of polydimethylsiloxane (PDMS) using soft lithography technology. The suspension format was based on the target proteins forming a sandwich structure between the magnetic beads and the quantum dot (QD) probes through specific antibody–antigen interactions. The planar microarray format was produced by fabricating an array of micro-wells in PDMS. Each micro-well was designed to trap a single microbead and eventually generated a microbead array within the PDMS chamber. The resultant bead-based on-chip assay could be used for simultaneously detecting three lung cancer biomarkers—carcinoembryonic antigen (CEA), fragments of cytokeratin 19 (CYFRA21-1) and neuron-specific enolase (NSE)—in 10 μl of human serum, with a wide linear dynamic range (1.03–111 ng/mL for CEA and CYFRA21-1; 9.26–1000 ng/ml for NSE) and a low detection limit (CEA: 0.19 ng/ml; CYFRA21-1: 0.97 ng/ml; NSE: 0.37 ng/ml; S / N =3). Our micro-well chip does not require complex e-beam lithography or the reactive ion etching process as with existing micro-well systems, which rely on expensive focused ion beam (FIB) milling or optical fiber bundles. Furthermore, the current approach is easy to operate without extra driving equipment such as pumps, and can make parallel detection for multiplexing with rapid binding kinetics, small reagent consumption and low cost. This work has demonstrated the importance of the successful application of on-chip multiplexing sandwich assays for the detection of biomarker proteins. [ABSTRACT FROM AUTHOR]

Background The B7 family member B7-H3 (CD276) is involved in tumor immunity including Non-small-cell lung cancer (NSCLC). We have previously demonstrated an elevated circulating level of the soluble form of B7-H3 (sB7-H3) in NSCLC patients. However, the expression of sB7-H3 in NSCLC-derived malignant pleural effusions (MPEs) and its clinical significance remain elusive. Methods We measured and compared sB7-H3 levels in NSCLC-derived MPEs (n = 52) and nonneoplastic pleural effusions (NPEs) (n = 47), and then evaluated the diagnostic performance for sB7-H3 in NSCLC-derived MPEs. The correlation between MPE-derived sB7-H3 and clinical characteristics including TNM staging system was also analyzed. Results The median value of sB7-H3 in 52 MPEs and 47 NPEs were 41.60 ng/ml (interquartile range: 36.76–51.30 ng/ml) and 31.55 ng/ml (interquartile range: 26.97–36.63 ng/ml) ( P < 0.0001 ), respectively. At the proposed cut-off value at 38.41 ng/ml, sB7-H3 was capable of discriminating NSCLC-derived MPEs from NPEs with a sensitivity of 67.3% and a specificity of 91.5% respectively. Furthermore, MPEs-derived sB7-H3 was correlated with smoking status ( P = 0.005 ), primary tumor size (T factor, P = 0.03 ), regional lymph node dissemination (N factor, P = 0.019 ) and distant metastasis (M factor, P = 0.009 ) of NSCLC patients. Conclusions Upregulated sB7-H3 expression in MPEs is correlated with TNM stage of NSCLC and may serve as a potential biomarker for NSCLC-derived MPEs. [ABSTRACT FROM AUTHOR]

The accurate determination of tumor biomarkers in blood is of vital significance in the diagnosis and therapy of tumor disease. In this research, an innovative sandwich-type electrochemical immunosensor is designed for the ultrasensitive determination of tumor biomarker AFP using spherical nucleic acids-templated silver nanoclusters (AgNCs) sensing platform. For this purpose, on one hand, DNA functionalized gold nanoparticles (AuNPs@DNA) is selected not only as the cross-linker to immobilize the primary antibody (anti-AFP antibody 1, Ab1) to obtain AuNPs@DNA-Ab1, but also as the template for synthesizing AgNCs on AuNPs to form AuNPs@DNA-AgNCs. On the other hand, p-sulfonated calix[4]arene (pSC 4) modified Au is chosen to immobilize the secondary antibody (anti-AFP antibody 2, Ab2) through host-guest recognition between Ab2 and pSC 4. When AFP is encountered, the immunoreaction signal can be significantly amplified by the electrochemical reduction of AgNCs. Under optimal circumstances, the sandwich-type electrochemical immunosensor exhibits broad limit of linearity from 0.001 to 100 ng mL−1 (R2 = 0.997) and low detection limit of 7.74 fg mL−1 (S/N = 3). The immunosensor possesses excellent repeatability and selectivity, offering a novel method for sensitive clinical diagnosis of tumor markers in human hepatocellular carcinoma. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a widely expressed multi-functional adhesion molecule reported to serve as a serum biomarker in several types of cancer. However, the serum CEACAM1 expression in breast cancer is unclear. We investigated the serum concentrations of CEACAM1 in patients with breast cancer and determine the potential of serum CEACAM1 as a breast cancer biomarker. Methods Serum specimens were obtained from 33 patients with breast cancer, 30 patients with benign breast diseases and 34 healthy donors. The serum CEACAM1 concentrations were examined by an enzyme-linked immunosorbent assay (ELISA). Results The serum CEACAM1 concentrations in the malignant group (532 ng/ml) were significantly higher than those of the benign group (423 ng/ml) and healthy control group (386 ng/ml) (both p < 0.001). Based on univariable logistic regression, serum CEACAM1 concentrations significantly predicted breast cancer versus normal controls or benign breast diseases. Area under receiver operating characteristic curve (ROC) for serum CEACAM1 was 0.925(95% CI: 0.866–0.984). The optimal cut-off concentration of CEACAM1 was 475.82 ng/ml for discriminating breast cancer from normal controls. Conclusion Serum concentrations of CEACAM1 may serve as a useful indicator for the presence of breast cancer. [ABSTRACT FROM AUTHOR]

Metastasis is a leading cause of cancer-related deaths. Hence, the discovery of more reliable metastasis-related biomarkers is crucial to improve the survival rate of cancer patients. W3 is an aptamer previously produced by the subtractive cell-SELEX using metastatic colorectal cancer cells as target cells and non-metastatic cells as negative cells. In this study, we aimed to evaluate whether the target molecule of W3 can potentially act as a metastatic biomarker. First, we obtained two cell subpopulations with different expression levels of the target molecule by W3-based cell sorting. Subsequently, we demonstrated that W3high cells have a higher metastatic potential than W3low cells both in vitro and in vivo. Further, immunohistochemical analysis revealed that W3 target expression is positively associated with metastasis and poor prognosis of CRC patients. Using mass spectrometry (MS) combined with pull-down, we identified that Ephrin type-A receptor 2 (EphA2) is the target of W3. EphA2's potential as a metastatic predictor was demonstrated by capturing W3-positive circulating tumor cells from CRC patients using a W3 probe. Based on these results, we put forward a stratagem for cell-SELEX-based biomarker discovery: selecting an aptamer through subtractive cell-SELEX towards the phenotype of interest; evaluating the functional phenotype of the target molecule by aptamer-based target cell sorting and analysis of clinical samples; and identifying the aptamer's target molecule using MS and aptamer-based target enrichment. This stratagem not only shortens the time for the clinical application of aptamers but also enables a more targeted and efficient discovery of biomarkers. [ABSTRACT FROM AUTHOR]

Objectives Mesenchymal–epithelial transition factor (MET) plays a critical role in the development and progression of lung cancer. We aimed to quantify the level of serum MET DNA, analyze its diagnostic value, and provide a novel biomarker for lung cancer. Methods Serum MET DNA was extracted from 95 patients with lung cancer, 10 with benign lung diseases, and 34 healthy volunteers. MET DNA was quantified using real-time fluorescent quantitative polymerase chain reaction (FQ-PCR). Data were analyzed using statistical software SPSS 17.0. Results Serum MET DNA level in the lung cancer group was higher than in the healthy group and benign lung diseases group. Serum MET DNA level was higher in lung cancers patients with smoking, squamous cell carcinoma, advanced TNM stage, and increased tumor size. The difference in serum MET DNA level was not related to sex, age, and lymph node metastasis among the lung cancer patients. The receiver operating characteristic curve showed a sensitivity of 72.6% and specificity of 90.9% for the ability of serum MET DNA to detect lung cancer at the cutoff value of 1.30 × 10 4 copies/μL. The association of serum MET DNA level with existing clinical lung tumor markers was analyzed, including neuron-specific enolase, squamous cell carcinoma antigen, and cytokeratin fragment 21-1. With the combination of serum MET DNA, the sensitivity was raised from 39.1%, 24.9%, 66.1% to 83.3%, 79.4% and 90.7%, respectively. Conclusions Quantification of serum MET DNA by FQ-PCR may serve as a novel accessible diagnostic tool for the clinical screening and detection of lung cancer. [ABSTRACT FROM AUTHOR]

Abstract: We examined the expression of carbonic anhydrase IX (CA IX) by immunohistochemical staining using monoclonal antibody M75 (Institute of Virology, Slovak Academy of Sciences, Bratislava) in a group of 38 fibroadenomas and 55 carcinomas of the breast. In each case, the intensity of staining, percentage of labeled cells and subcellular localization of CA IX were assessed. CA IX was detected in 11/38 fibroadenomas (28.9%). Weak cytoplasmic positivity was dominant in these positive cases. Immunohistochemical analysis of 55 carcinomas showed CA IX expression in 34 cases (61.8%). Membrane staining alone was observed in 27/55 carcinomas (49.1%), while cytoplasmic positivity was found in 4/55 cases (7.3%). Combined membrane and cytoplasmic immunostaining of CA IX was detected in 3/55 carcinomas (5.4%). The intensity of immunoreactivity varied from weak to strong. Under 50% of reactive cells were found in 9/38 fibroadenomas (23.6%) and in 29/55 carcinomas (52.7%). More than 50% of reactive cells were found in 2/38 fibroadenomas (5.3%) and in 5/55 carcinomas (9.1%). Statistical analysis confirmed significant differences in the subcellular localization, intensity of immunoreactivity and percentage of labeled cells in fibroadenomas and carcinomas (p <0.05). Our results confirmed the hypothesis that expression of CA IX may represent a valuable tumor biomarker as well as a promising diagnostic and prognostic parameter in breast cancer. [Copyright &y& Elsevier]

Summary: Background: Tumor biomarkers are commonly used for cancer screening and as indicators of treatment effects. We recently reported that urine porphyrin levels from tumor-bearing mice were elevated compared with those from normal mice after administration of 5-aminolevulinic acid (ALA). In the present study, we evaluated the use of urine samples from bladder cancer patients as tumor biomarkers. Methods: ALA, 1.0g, was orally administered to 66 bladder cancer patients and 20 healthy adults. The urine concentrations of uroporphyrin I (UPI), uroporphyrin III (UPIII), coproporphyrin I (CPI), coproporphyrin III (CPIII), and total porphyrins were measured using High Performance Liquid Chromatography (HPLC) system. Results: Almost all of the urinary porphyrin concentrations from the patients with bladder cancer were higher than those from healthy adults. Moreover, 8h after ALA administration, urinary UPI and CPI showed high sensitivity (100 for UPI and CPI) and specificity (96.4 for UPI and 91.4 for CPI). Conclusion: These results indicate that the presence of urinary porphyrins after administration of ALA may function as tumor biomarkers. This method represents a possible new tumor screening method called photodynamic screening (PDS) using ALA-induced porphyrins. [Copyright &y& Elsevier]

Abstract: We previously reported that α(1,6)fucosyltransferase (Enzyme class 2.4.1.68) activity and expression are increased in colorectal cancer, suggesting a role for this enzyme in tumor development and progression. However, the possible impact of α(1,6)fucosyltransferase activity or expression on clinical outcomes in colorectal cancer patients has never been studied. Thus, the present study was conducted to determine the value of α(1,6)fucosyltransferase as a prognostic factor for colorectal cancer. α(1,6)Fucosyltransferase expression was analyzed using immunohistochemistry in 141 colorectal tumors, and α(1,6)fucosyltransferase activity was determined in 39 tumors. A complete standardized follow-up of patients was documented until the end of the observation period of 5 years or patient death. Univariate analysis demonstrated the absence of a correlation between enzyme activity and disease evolution. However, in patients with moderate or strong α(1,6)fucosyltransferase expression, a significant decrease in the overall (P = .04) and disease-free (P = .03) survival rates was observed. In addition, when local and distant disease recurrence were considered separately, enzyme expression was found to correlate with local tumor recurrences (P = .01). Furthermore, multivariate analysis showed that α(1,6)fucosyltransferase expression has independent value for predicting tumor recurrences and, specifically, local recurrences. These findings suggest that α(1,6)fucosyltransferase expression may be a good indicator of poor prognosis in colorectal cancer and, therefore, a helpful tool to choose the most effective treatment. [Copyright &y& Elsevier]

Purpose: The ability to predict which men will experience biochemical recurrence (BCR) after salvage radiation therapy (SRT) for recurrent prostate cancer (PCa) remains less than optimal. Related to this, novel targets for adjuvant therapies are also lacking. Here, we evaluate the association of B7-H3 expression in primary PCa tumors and BCR after SRT. Methods and Materials: We identified 148 patients who received SRT between July 1987 and July 2003. Expression of B7-H3 in primary PCa tumors was detected using a monoclonal antibody. The staining levels were quantified via visual assessment and categorized as weak, moderate, or marked. Relative risks (RRs) and 95% confidence intervals (CIs) from Cox proportional hazards models were used to examine the association between B7-H3 staining and BCR. Results: With a median follow-up of 6.2 years (minimum, 0.6; maximum, 14.7), 78 patients (53%) experienced BCR. In single-variable analysis, there was evidence of an increased risk of BCR for patients with moderate (RR, 2.25; 95% CI, 1.24–4.09, p = 0.008) and marked (RR, 4.40, 95% CI, 2.29–8.43, p < 0.001) B7-H3 staining compared with weak staining. This evidence remained, albeit weaker, after adjustment for additional clinicopathologic covariates (RR, 1.82, p = 0.068 [moderate vs. weak]; RR, 2.87, p = 0.003 [marked vs. weak]). Conclusion: This is the first report that higher tumor B7-H3 staining in primary PCa tumors is associated with increased risk of BCR after SRT. Future studies involving larger numbers of patients are required to validate these results and also to explore possible means of targeting B7-H3 in an adjuvant setting. [ABSTRACT FROM AUTHOR]

Abstract: Objectives : The change in DNA methylation patterns can be used to distinguish between normal and cancer cells. The aim of the present study was to examine the 5′ CpG island methylation patterns of the cancer-testis antigen (CT antigen) gene family, MAGE-As, in hepatocellular carcinoma (HCC), and to develop the DNA demethylation pattern as a novel tumor biomarker. Methods : We used bisulfite-sequencing PCR (BSP) to map the methylation status of the CpG site among the promoter of the MAGE-A gene family in several HCC cell lines including Hep G2, BEL7402, BEL7404, and BEL7407, and normal peripheral blood white blood cells (WBCs). According to differences of the methylation pattern between HCC cell lines and the control, methylation-special PCRs (MSP) have been developed. The developed MSPs were used to detect the paraffin-embedded slices that were pathologically diagnosed as HCC, hepatocirrhosis, hepatitis, and healthy. Results : We found that several CpG sites among the MAGE-A1 and MAGE-A3 promoters have different methylation patterns in the HCC cell lines as compared to those in normal WBCs. Two sets of MSP primers were designed to distinguish the HCC genomic DNA and normal control cell genomic DNA as novel tumor biomarkers, and the biomarkers were validated on the archived paraffin sections of liver primary tissue. In the detection of 34 HCCs and 17 tumor-free liver tissues, the clinical sensitivity and specificity were 91.2% and 100%, respectively. Conclusion : Detection of aberrant methylation patterns of MAGEs CpG islands using MSP may be useful for diagnosis of HCC. [Copyright &y& Elsevier]

Tumors are the leading killers of human health, however, diagnosis on tumors are neither timely nor accurate due to the high detection cost and high technical requirements. For cancer diagnosis and treatment, self-powered biosensors based on enzymatic biofuel cells have the advantages of simple structure, easy miniaturization, instantaneous response to analytes, and high economic applicability. It is of great significance for the development of portable and personalized biosensors. Over the past twenty years, a number of prominent self-powered biosensors have been created to diagnose tumor via analyzing the corresponding biomarkers with low cost. What's more, some intelligent self-powered biosensors with integrated diagnostic and therapeutic functions have also been reported. In this review, the focus of this work is on the development of self-powered biosensors in tumor diagnosis and intelligent regulation from the aspects of design and working principles. Furthermore, the challenge for the future work is also analyzed. • Tumors severely threaten human health, yet the potential threats are unreported due to the high detection costs. • SPBs are promising portable and personalized analytical instruments. • The applications of SPBs in tumor diagnosis maintain steady and rapid growth. • The SPBs with intelligent health monitoring and regulation functions are promising economical and portable medical devices. [ABSTRACT FROM AUTHOR]

• This study proposes a predictive system based on serum biomarkers and ensemble learning for early colorectal cancer diagnosis in mass screening based on 17 serum biomarkers; the system consists of a binary predictor, which predicts the presence/absence of colorectal cancer, and a staging predictor, which predicts the related TNM stage. • Plasmatic proteins revealed to be significant in predicting the absence/presence and the related TNM stage of colorectal cancer in patients. • Ceruloplasmin and α -2-Macroglobulin are significant in predicting the early colorectal cancer presence/absence outcome through XGBoost and Random Forest models, while CA 50 and α -2-Antitrypsin can be neglected. • Extended reality allows interpreting the significance of serum biomarkers in performing early colorectal cancer diagnosis through the predictors' bias-variance ratio. • Ensemble learning through majority voting permits to reduce the noise in the prediction of early colorectal cancer presence/absence outcome. Background and objective : Colorectal cancer is one of the most common malignancies among the general population. Artificial Intelligence methodologies based on serum parameters are in continuous development to obtain less expensive tools for highly sensitive diagnoses. This study proposes a predictive system based on serum biomarkers and ensemble learning to predict colorectal cancer presence and the related TNM stage in patients. Methods : We have selected 17 significant plasmatic proteins, i.e., Carcinoembryonic Antigen, CA 19-9, CA 125, CA 50, CA 72-4, Tissue Polypeptide Antigen, C-Reactive Protein, Ceruloplasmin, Haptoglobin, Transferrin, Ferritin, α -1-Antitrypsin, α -2-Macroglobulin, α -1 Acid Glycoprotein, Complement C4, Complement C3, and Retinol Binding Protein, regarding 345 patients (248 affected by the neoplastic disease). The proposed system consists of two predictors, i.e., binary and staging; the former predicts the presence/absence of cancer, while the latter identifies the related TNM stage (I, II, III, or IV). The experiments were conducted by deploying and comparing Random Forest, XGBoost, Support Vector Machine, and Multilayer Perceptron with feature selection based on Gini Importance and with dimensionality reduction via PCA. Results : The results show that the system composed of XGBoost as binary and staging predictor reaches 91.30% accuracy, 90% sensitivity, and 93.33% specificity for the absence/presence outcome, while 66.66% accuracy for the staging response. With the expansion of the training set in favor of positive patients and majority voting, the system composed of the combination of Support Vector Machine, XGBoost, and Multilayer Perceptron as the binary predictor reaches 98.03% accuracy, 100% sensitivity, and 92.30% specificity, while the combination of Random Forest, XGBoost, and Multilayer Perceptron as staging predictor achieves 60% accuracy. The final system reaches, in terms of accuracy, 98.03%, and 66.66% for the binary and staging predictors, respectively. It was also found that the biomarkers which contribute most to the binary decision are Ceruloplasmin and α -2-Macroglobulin, while the least significant dimensions are CA 50 and α -1-Antitrypsin; instead, Carcinoembryonic Antigen and α -1 Acid Glycoprotein are the most significant to the staging decision. Conclusions : The present study proves the effectiveness of deploying serum biomarkers as feature dimensions for early colorectal cancer diagnosis and of using majority voting for noise reduction in the prediction. [ABSTRACT FROM AUTHOR]

Biomarkers play an important role in disease diagnosis and prognosis, which demand reliable, sensitive, rapid, and economic detection platform to conduct simultaneous multiple-biomarkers analysis in serum or body liquid. Here, we developed a universal biosensing platform through integrating the advantages of unique nanostructure and biochemistry properties of graphene oxide quantum dots and high throughput and low cost of microfluidic chip for reliable and simultaneous detection of multiple cancer antigen and antibody biomarkers. The performance of the proposed biosensing platform is validated through the representative cancer biomarkers including carcino-embryonic antigen (CEA), carbohydrate antigen 125 (CA125), α-fetoprotein (AFP), carbohydrate antigen 199 (CA199) and carbohydrate antigen 153 (CA153). It has a large linear quantification detection regime of 5–6 orders of magnitude and an ultralow detection limit of 1 pg/mL or 0.01 U/mL. Moreover, the proposed biosensing chip is capable of conducting 5–20 kinds of biomarkers from at least 60 persons simultaneously in 40 min with only 2 μL serum of each patient, which essentially reduces the detection cost and time to at least 1/60 of current popular methods. Clinical breast cancer and healthy samples detection results indicated its promising perspective in practical applications including cancer early diagnosis, prognosis, and disease pathogenesis study. [Display omitted] • An ultrasensitive, multiple biomarkers simultaneous detection biochip was reported. • Microfluidic integrated with QDs to realize the high-performance biosensing platform. • The biochip has an ultralow LOD (1 pg/mL), a broad dynamic range and high-throughput. • Healthy and cancerous serums were diagnosed by the biochip successfully. [ABSTRACT FROM AUTHOR]

Late diagnosis of pancreatic ductal adenocarcinoma (PDA) is one of the reasons of its low 5-year survival rate and it is due to its unspecific symptoms during the first stages of the disease and the lack of reliable serological markers. Since PDA shows an altered glycan expression, here we have focused on finding novel potential biomarkers, namely glycoproteins that express the tumor associated carbohydrate structure sialyl-Lewis x (sLex), which is described in PDA. Through a glycoproteomic approach, we have analyzed target proteins containing sLex from PDA tissues by 2DE and immunodetection techniques, and have identified by mass spectrometry the protein MFAP4 as a carrier of sLex in PDA. MFAP4 showed a higher expression in PDA tissues compared with pancreatic control tissues. In addition, the colocalization of sLex over MFAP4 was found only in PDA and not in control pancreatic tissues. The analysis of MFAP4 expression in PDA cell lines and their secretome, in combination with immunohistochemistry of pancreatic tissues, revealed that MFAP4 was not produced by PDA cells, but it was found in the pancreatic extracellular matrix. The specificity of MFAP4 glycoform containing sLex in PDA tissues shows its relevance as a potential PDA biomarker. Despite advances in the field of cancer research, pancreatic ductal adenocarcinoma (PDA) lacks of a specific and sensitive biomarker for its early detection, when curative resection is still possible before metastases arise. Thus, efforts to discover new PDA biomarkers represent the first line in the fight against the increase of its incidence reported in recent years. Glycan alterations on glycoconjugates, such as glycoproteins have emerged as a rich source for the identification of novel cancer markers. In the present work, we aimed to shed light on novel biomarkers based on altered glycosylation in PDA, in particular those glycoproteins of PDA tissues carrying the tumor carbohydrate antigen sialyl-Lewis x (sLex). Through a glycoproteomic approach, we have shown that the glycoprotein MFAP4 carries sLex in PDA tissues and not in control pancreatic tissues. MFAP4 is found in the extracellular matrix in PDA and although its role in cancer progression is unclear, its sLex glycoform could be a potential biomarker in pancreatic ductal adenocarcinoma. Unlabelled Image • MFAP4 is a carrier of sLex in pancreatic adenocarcinoma (PDA). • MFAP4 is not produced by pancreatic cancer cells but it is found in the PDA stroma. • MFAP4-sLex glycoform is only found in PDA and not in pancreatic control samples. • MFAP4-sLex glycoform may have a role interacting with the PDA dense fibrotic stroma and ECM proteins [ABSTRACT FROM AUTHOR]

• RCA was integrated into magnetic immunoassay in ICP-MS, which achieve the tumor biomarker for clinical diagnosis. • Proposed detection methods have fast, simple, sensitive and accurate features. • The detection platform could detect as low as low as 2 pg/mL AFP and 5 pg/mL CEA, respectively within 60 min. • This method could be applied in the real clinical samples which rivalled ELISA. Herein, we constructed magnetic immunoassay-based diagnostic platform for cancer biomarker of patient' s sample by coupling rolling circular amplification with ICP-MS. Tumor biomarker (alpha-fetoprotein, AFP, Carcinoembryonic antigen, CEA) from clinical sample was initially captured by biotinylated antibody functionalized on the surface of magnetic beads, and then recognized by a secondary antibody that linked with a RCA(Rolling Circular Amplification)-primer. Up addition of RCA-template and DNA polymerase, one single target recognition event can be converted into multiple predesigned DNA sequences. This specific sequence can be hybridized with DNA-conjugated AuNPs and form a DNA-AuNP complex for ICP-MS measurement. Under the optimal experimental parameters, this platform can detect AFP and CEA in 20% serum, as low as 2 pg/mL and 5 pg/mL, respectively, which rivalled ELISA. We anticipate this methodology for tumor biomarker detection can be used for clinical diagnosis in future. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PaCa) is considered an aggressive but still asymptomatic malignancy. Due to the lack of effective diagnostic markers, PaCa is often diagnosed during late metastatic stages. Besides surgical resection, no other treatment appears to be effective during earlier stages of the disease. Exosomes are related to a class of nanovesicles coated by a bilayer lipid membrane and enriched in protein, nucleic acid, and lipid contents. They are widely present in human body fluids, including blood, saliva, and pancreatic duct fluid, with functions in signal transduction and material transport. A large number of studies have suggested for a crucial role for exosomes in PaCa, which may be utilized to improve its future diagnosis and treatment, but the underlying molecular mechanisms as well as their potential clinical applications are largely unknown. By collecting and analyzing the most up-to-date literature, here we summarize the current progress of the clinical applications related to exosomes in PaCa. Therefore, we presently provide some rationale for the potential value of exosomes in PaCa, thereby promoting putative applications in targeted PaCa treatment. [ABSTRACT FROM AUTHOR]

Keratins are essential elements of the cytoskeleton of normal and malignant epithelial cells. Because carcinomas commonly maintain their specific keratin expression pattern during malignant transformation, keratins are extensively used as tumor markers in cancer diagnosis including the detection of circulating tumor cells in blood of carcinoma patients. Interestingly, recent biological insights demonstrate that epithelial keratins should not only be considered as mere tumor markers. Emerging evidence suggests an active biological role of keratins in tumor cell dissemination and metastasis. In this review, we illustrate the family of keratin proteins, summarize the latest biological insights into keratin function related to cancer metastasis and discuss the current use of keratins for detection of CTCs and other blood biomarkers used in oncology. [ABSTRACT FROM AUTHOR]