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Fucosylation is involved in cancer and inflammation, and several fucosylated proteins, such as AFP-L3 for hepatocellular carcinoma, are used as cancer biomarkers. We previously reported an increase in serum fucosylated haptoglobin (Fuc-Hp) as a biomarker for several cancers, including pancreatic and colon cancer and hepatocellular carcinoma. The regulation of fucosylated protein production is a complex cellular process involving various fucosylation regulatory genes. In this report, we investigated the molecular mechanisms regulating Fuc-Hp production in cytokine-treated hepatoma cells using a partial least squares (PLS) regression model. We found that SLC35C1, which encodes GDP-fucose transporter 1 (GFT1), is the most responsible factor for Fuc-Hp production among various fucosylation regulatory genes. Furthermore, the transcription factor SP1 was essential in regulating SLC35C1 expression. We also found that an SP1 inhibitor was able to suppress Fuc-Hp production without affecting total Hp levels. Taken together, Fuc-Hp production was regulated by SP1 via induction of GFT1 in the hepatoma cell line HepG2.

Abstract Background Telomerase is a ribonucleoprotein complex consisting of a catalytic component telomerase reverse transcriptase (TERT), internal RNA template and other co‐factors, and its essential function is to synthesize telomeric DNA, repetitive TTAGGG sequences at the termini of linear chromosomes. Telomerase is silent in normal human follicular thyroid cells, primarily due to the TERT gene being tightly repressed. During the development and progression of thyroid carcinomas (TCs), TERT induction and telomerase activation is in general required to maintain telomere length, thereby conferring TC cells with immortal and aggressive phenotypes. Methods The genomic alterations of the TERT loci including TERT promoter's gain‐of‐function mutations, copy number gain, fusion and rearrangements, have recently been identified in TCs as mechanisms to induce TERT expression and to activate telomerase. Importantly, numerous studies have consistently shown that TERT promoter mutations and TERT expression occur in all TC subtypes, and are robustly associated with TC malignancy, aggressiveness, treatment failure and poor outcomes. Therefore, the assessment of TERT promoter mutations and TERT expression is highly valuable in TC diagnostics, prognosis, treatment decision, and follow‐up design. In addition, the TERT promoter is frequently hypermethylated in TC cells and tumors, which is required to activate TERT transcription and telomerase. Dysregulation of other components in the telomerase complex similarly upregulate telomerase. Moreover, shortened telomeres lead to altered gene expression and metabolism, thereby actively promoting TC aggressiveness. Here we summarize recent findings in TCs to provide the landscape of TC‐featured telomere/telomerase biology and discuss underlying implications in TC precision medicine. Conclusion Mechanistic insights into telomerase activation and TERT induction in TCs are important both biologically and clinically. The TERT gene aberration and expression‐based molecular classification of TCs is proposed, and for such a purpose, the standardization of the assay and evaluation system is required. Moreover, the TERT‐based system and 2022 WHO TC classification may be combined to improve TC care.

Apolipoproteins (APOs), the primary protein moiety of lipoproteins, are known for their crucial role in lipid traffic and metabolism. Despite extensive exploration of APOs in cardiovascular diseases, their roles in cancers did not attract enough attention. Recently, research focusing on the roles of APOs in cancers has flourished. Multiple studies demonstrate the interaction of APOs with classical pathways of tumorigenesis. Besides, the dysregulation of APOs may indicate cancer occurrence and progression, thus serving as potential biomarkers for cancer patients. Herein, we summarize the mechanisms of APOs involved in the development of various cancers, their applications as cancer biomarkers and their genetic polymorphism associated with cancer risk. Additionally, we also discuss the potential anti-cancer therapies by virtue of APOs. The comprehensive review of APOs in cancers may advance the understanding of the roles of APOs in cancers and their potential mechanisms. We hope that it will provide novel clues and new therapeutic strategies for cancers.

Long non-coding RNAs (lncRNAs) have been found to play essential roles in the cell proliferation, fission and differentiation, involving various processes in humans. Recently, there is more and more interest in exploring the relationship between lncRNAs and tumors. Many latest evidences revealed that LINC00467, an oncogenic lncRNA, is highly expressed in lung cancer, gastric cancer, colorectal cancer, hepatocellular carcinoma, breast cancer, glioblastoma, head and neck squamous cell carcinoma, osteosarcoma, and other malignant tumors. Besides, LINC00467 expression was linked with proliferation, migration, invasion and apoptosis via the regulation of target genes and multiple potential pathways. We reviewed the existing data on the expression, downstream targets, molecular mechanisms, functions, relevant signaling pathways, and clinical implications of LINC00467 in various cancers. LINC00467 may serve as a novel biomarker or therapeutic target for the diagnosis and prognosis of various human tumors. [ABSTRACT FROM AUTHOR]

Clinical diagnostics rely heavily on the detection and quantification of cancer biomarkers. The rapid detection of cancer-specific biomarkers is of great importance in the early diagnosis of cancers and plays a crucial role in the subsequent treatments. There are several different detection techniques available today for detecting cancer biomarkers. Because of target-related conformational alterations, high stability, and target variety, aptamers have received considerable interest as a biosensing system component. To date, several sensitivity-enhancement strategies have been used with a broad spectrum of nanomaterials and nanoparticles (NPs) to improve the limit and sensitivity of analyte detection in the construction of innovative aptasensors. The present article aims to outline the research developments on the potential of DNAzymes-based aptasensors for cancer biomarker detection. [ABSTRACT FROM AUTHOR]

Simple Summary: Uveal melanoma is an aggressive cancer that begins in the eye, but often spreads to distant organs when tumor cells enter the blood. Disease spreads in nearly half of uveal melanoma patients, and is fatal. We discovered a new tumor cell population in the blood stream of cancer patients that has combined tumor cell and white blood cell features. These cells, called circulating hybrid cells, can develop into metastatic tumors. Recently, we detected circulating hybrid cells in the blood of patients with uveal melanoma. In this study we determine that the number of circulating hybrid cells in the blood at time of initial treatment of uveal melanomas predicts future development of disease spread. Circulating hybrid cells have promise as a non-invasive and repeatable "liquid biopsy" for uveal melanoma patients. Therefore, study of this newly discovered cancer cell will improve understanding of the biology of disease progression in uveal melanoma. Background: Uveal melanoma is an aggressive cancer with high metastatic risk. Recently, we identified a circulating cancer cell population that co-expresses neoplastic and leukocyte antigens, termed circulating hybrid cells (CHCs). In other cancers, CHCs are more numerous and better predict oncologic outcomes compared to circulating tumor cells (CTCs). We sought to investigate the potential of CHCs as a prognostic biomarker in uveal melanoma. Methods: We isolated peripheral blood monocular cells from uveal melanoma patients at the time of primary treatment and used antibodies against leukocyte and melanoma markers to identify and enumerate CHCs and CTCs by immunocytochemistry. Results: Using a multi-marker approach to capture the heterogeneous disseminated tumor cell population, detection of CHCs was highly sensitive in uveal melanoma patients regardless of disease stage. CHCs were detected in 100% of stage I-III uveal melanoma patients (entire cohort, n = 68), whereas CTCs were detected in 58.8% of patients. CHCs were detected at levels statically higher than CTCs across all stages (p = 0.05). Moreover, CHC levels, but not CTCs, predicted 3 year progression-free survival (p < 0.03) and overall survival (p < 0.04). Conclusion: CHCs are a novel and promising prognostic biomarker in uveal melanoma. [ABSTRACT FROM AUTHOR]

Analysis of cancer biomarkers has enormous promise for advancing our molecular understanding of illness and facilitating more precise and timely diagnosis and follow-up care. MicroRNA, exosomes, ctDNA, CTCs, and proteins are only some of the circulating biomarkers that can be detected by liquid biopsy instead of the more intrusive and time-consuming process of doing a tissue biopsy. As the cancer diagnosis bio-markers reveal ultra-low levels in the early stages of the disease, highly sensitive approaches are urgently required. Researchers have taken an interest in a optical biosensor for detecting cancer biomarkers as a potential tool for early disease diagnosis. These techniques have the potential to aid in the development of effective treatments, ultimately leading to a higher rate of patient survival. This review briefly discuss the i) understanding of cancer and biomarkers for early diagonosis purpose ii) Molecular methods and ii) biosensor-based diagnostics. The reseach primary focus on advancement in biosensor design using various concepts ie., Electrochemical, Chemiluminescence and Colorimetric, Surface plasmons (SP), Surface plasmon resonance (SPR), localized surface plasmon resonance (LSPR), Fluorescence, Fiber-based sensors, Terahertz based biosensors, and Surface enhanced Raman spectroscopy (SERS). As a result of the local electric field amplification around plasmonic (usually gold and silver) nanostructures, surface-enhanced Raman spectroscopy (SERS) has emerged as a rapid, selective, and sensitive alternative to conventional laboratory analytical methods, making significant strides in a number of biosensing applications but still under developing stage to be used as diagnostic tool in clinical research. [ABSTRACT FROM AUTHOR]

Background: Early identification of patients who will benefit from immune checkpoint inhibitors (ICIs) has recently become a hot issue in cancer immunotherapy. Peripheral cytokines are key regulators in the immune system that can induce the expression of immune checkpoint molecules; however, the association between peripheral cytokines and the efficiency of ICIs remains unclear. Methods: A systematic review was conducted in several public databases from inception through 3 February 2022 to identify studies investigating the association between peripheral cytokines (i.e., IL-1β, IL-2, IL-2RA, IL-2R, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF-α, IFN-γ, and TGF-β) and ICI treatment. Survival data, including overall survival (OS) and/or progression-free survival (PFS), were extracted, and meta-analyses were performed. Results: Twenty-four studies were included in this analysis. The pooled results demonstrated that the pretreatment peripheral levels of IL-6 (univariate analysis: HR = 2.53, 95% CI = 2.21-2.89, p < 0.00001; multivariate analysis: HR = 2.21, 95% CI = 1.67-2.93, p < 0.00001) and IL-8 (univariate analysis: HR = 2.17, 95% CI = 1.98-2.38, p < 0.00001; multivariate analysis: HR = 1.88, 95% CI= 1.70-2.07, p < 0.00001) were significantly associated with worse OS of cancer patients receiving ICI treatment in both univariate and multivariate analysis. However, high heterogeneity was found for IL-6, which might be attributed to region, cancer type, treatment method, sample source, and detection method. Conclusion: The peripheral level of IL-8 may be used as a prognostic marker to identify patients with inferior response to ICIs. More high-quality prospective studies are warranted to assess the predictive value of peripheral cytokines for ICI treatment. [ABSTRACT FROM AUTHOR]

Glycosylation is one of the most important post-translational modifications (PTMs) in a protein, and is the most abundant and diverse biopolymer in nature. Glycans are involved in multiple biological processes of cancer initiation and progression, including cell-cell interactions, cell-extracellular matrix interactions, tumor invasion and metastasis, tumor angiogenesis, and immune regulation. As an important biomarker, tumor-associated glycosylation changes have been extensively studied. This article reviews recent advances in glycosylation-based biomarker research, which is useful for cancer diagnosis and prognostic assessment. Truncated O-glycans, sialylation, fucosylation, and complex branched structures have been found to be the most common structural patterns in malignant tumors. In recent years, immunochemical methods, lectin recognition-based methods, mass spectrometry (MS)-related methods, and fluorescence imaging-based in situ methods have greatly promoted the discovery and application potentials of glycomic and glycoprotein biomarkers in various cancers. In particular, MSbased proteomics has significantly facilitated the comprehensive research of extracellular glycoproteins, increasing our understanding of their critical roles in regulating cellular activities. Predictive, preventive and personalized medicine (PPPM; 3P medicine) is an effective approach of early prediction, prevention and personalized treatment for different patients, and it is known as the new direction of medical development in the 21st century and represents the ultimate goal and highest stage of medical development. Glycosylation has been revealed to have new diagnostic, prognostic, and even therapeutic potentials. The purpose of glycosylation analysis and utilization of biology is to make a fundamental change in health care and medical practice, so as to lead medical research and practice into a new era of 3P medicine. [ABSTRACT FROM AUTHOR]

Blood group antigen is a class of heritable antigenic substances present on the erythrocyte membrane. However, the role of blood group antigens in cancer prognosis is still largely unclear. In this study, we investigated the expression of 33 blood group antigen genes and their association with the prognosis of 30 types of cancers in 31,870 tumor tissue samples. Our results revealed that blood group antigens are abnormally expressed in a variety of cancers. The high expression of these antigen genes was mainly related to the activation of the epithelial-mesenchymal transition (EMT) pathway. High expression of seven antigen genes, i.e., FUT7, AQP1, P1, C4A, AQP3, KEL and DARC, were significantly associated with good OS (Overall Survival) in six types of cancers, while ten genes, i.e., AQP1, P1, C4A, AQP3, BSG, CD44, CD151, LU, FUT2, and SEMA7A, were associated with poor OS in three types of cancers. Kidney renal clear cell carcinoma (KIRC) is associated with the largest number (14 genes) of prognostic antigen genes, i.e., CD44, CD151, SEMA7A, FUT7, CR1, AQP1, GYPA, FUT3, FUT6, FUT1, SLC14A1, ERMAP, C4A, and B3GALT3. High expression of SEMA7A gene was significantly correlated with a poor prognosis of KIRC in this analysis but has not been reported previously. SEMA7A might be a putative biomarker for poor prognosis in KIRC. In conclusion, our analysis indicates that blood group antigens may play functional important roles in tumorigenesis, progression, and especially prognosis. These results provide data to support prognostic marker development and future clinical management. [ABSTRACT FROM AUTHOR]

The field of single-cell analysis has advanced rapidly in the last decade and is providing new insights into the characterization of intercellular genetic heterogeneity and complexity, especially in human cancer. In this regard, analyzing single circulating tumor cells (CTCs) is becoming particularly attractive due to the easy access to CTCs from simple blood samples called "liquid biopsies". Analysis of multiple single CTCs has the potential to allow the identification and characterization of cancer heterogeneity to guide best therapy and predict therapeutic response. However, single-CTC analysis is restricted by the low amounts of DNA in a single cell genome. Whole genome amplification (WGA) techniques have emerged as a key step, enabling single-cell downstream molecular analysis. Here, we provide an overview of recent advances in WGA and their applications in the genetic analysis of single CTCs, along with prospective views towards clinical applications. First, we focus on the technical challenges of isolating and recovering single CTCs and then explore different WGA methodologies and recent developments which have been utilized to amplify single cell genomes for further downstream analysis. Lastly, we list a portfolio of CTC studies which employ WGA and single-cell analysis for genetic heterogeneity and biomarker detection. [ABSTRACT FROM AUTHOR]

Rapid and sensitive detection of cancer biomarkers is crucial for cancer screening, early detection, and improving patient survival rate. The present study proposes an electrochemical gene-sensor capable of detecting tumor related TP53 gene mutation hotspots by self-assembly of sulfhydryl ended hairpin DNA probes tagged with methylene blue (MB) onto a gold electrode. By performing a hybridization reaction with the target DNA sequence, the gene-sensor can rearrange the probe's structure, resulting in significant electrochemical signal differences by differential pulse voltammetry. When the DNA biosensor is hybridized with 1 μM target DNA, the peak current response signal can decrease more than 60%, displaying high sensitivity and specificity for the TP53 gene. The biosensor achieved rapid and sensitive detection of the TP53 gene with a detection limit of 10 nmol L−1, and showed good specific recognition ability for single nucleotide polymorphism (SNP) and base sequence mismatches in the TP53 gene affecting residue 248 of the P53 protein. Moreover, the biosensor demonstrated good reproducibility, repeatability, operational stability, and anti-interference ability for target DNA molecule in the complex system of 50% fetal bovine serum. The proposed biosensor provides a powerful tool for the sensitive and specific detection of TP53 gene mutation hotspot sequences and could be used in clinical samples for early diagnosis and detection of cancer. [ABSTRACT FROM AUTHOR]

Early detection of cancer is vital for increasing patient survivability chances. The three major techniques used to diagnose cancers are instrumental examination, tissue biopsy, and tumor biomarker detection. Circulating tumor DNA (ctDNA) has gained much attention in recent years due to advantages over traditional technology, such as high sensitivity, high specificity, and noninvasive nature. Through the mechanism of apoptosis, necrosis, and circulating exosome release in tumor cells, ctDNA can spread throughout the circulatory system and carry modifications such as methylations, mutations, gene rearrangements, and microsatellite instability. Traditional gene-detection technology struggles to achieve real-time, low-cost, and portable ctDNA measurement, whereas electrochemical biosensors offer low cost, high specificity alongside sensitivity, and portability for the detection of ctDNA. Therefore, this review focuses on describing the recent advancements in ctDNA biomarkers for various cancer types and biosensor developments for real-time, noninvasive, and rapid ctDNA detection. Further in the review, ctDNA sensors are also discussed in regards to their selections of probes for receptors based on the electrode surface recognition elements.

Introduction: Gastric cancer remains a formidable challenge in oncology with high mortality rates and few advancements in treatment. Claudin-18.2 (CLDN18.2) is a tight junction protein primarily expressed in the stomach and is frequently overexpressed in certain subsets of gastric cancers. Targeting CLDN18.2 with monoclonal antibodies, such as zolbetuximab (IMAB362), has shown promising efficacy results in combination with chemotherapy., Areas Covered: The molecular cell biology of CLDN18.2 is discussed along with studies demonstrating the utility of CLDN18.2 expression as a biomarker and therapeutic target. Important clinical studies are reviewed, including Phase III trials, SPOTLIGHT and GLOW, which demonstrate the efficacy of zolbetuximab in combination with chemotherapy in patients with CLDN18.2-positive advanced gastric cancer., Expert Opinion: CLDN18.2 is involved in gastric differentiation through maintenance of epithelial barrier function and coordination of signaling pathways, and its expression in gastric cancers reflects a 'gastric differentiation' program. Targeting Claudin-18.2 represents the first gastric cancer specific 'targeted' treatment. Further studies are needed to determine its role within current gastric cancer treatment sequencing, including HER2-targeted therapies and immunotherapies. Management strategies will also be needed to better mitigate zolbetuximab-related treatment side effects, including gastrointestinal (GI) toxicities.

Combining omics data from different layers using integrative methods provides a better understanding of the biology of a complex disease such as cancer. The discovery of biomarkers related to cancer development or prognosis helps to find more effective treatment options. This study integrates multi-omics data of different cancer types with a network-based approach to explore common gene modules among different tumors by running community detection methods on the integrated network. The common modules were evaluated by several biological metrics adapted to cancer. Then, a new prognostic scoring method was developed by weighting mRNA expression, methylation, and mutation status of genes. The survival analysis pointed out statistically significant results for GNG11, CBX2, CDKN3, ARHGEF10, CLN8, SEC61G and PTDSS1 genes. The literature search reveals that the identified biomarkers are associated with the same or different types of cancers. Our method does not only identify known cancer-specific biomarker genes, but also proposes new potential biomarkers. Thus, this study provides a rationale for identifying new gene targets and expanding treatment options across cancer types.

In recent years PIWI-interacting RNAs (piRNAs) have gained the interest of scientists, mainly because of their possible implications in cancer. Many kinds of research showed how their expression can be linked to malignant diseases. However, most of them evaluated the expression of piRNAs in tumor tissues. It was shown how these non-coding RNAs can interfere with many signaling pathways involved in the regulation of proliferation or apoptosis. A comparison of piRNA expression in tumor tissue and adjacent healthy tissues has demonstrated they can be used as biomarkers. However, this way of obtaining samples has a significant drawback, which is the invasiveness of such a procedure. Liquid biopsy is an alternative for acquiring biological material with little to no harm to a patient. Several different piRNAs in various types of cancer were shown to be expressed in bodily fluids such as blood or urine. Furthermore, their expression significantly differed between cancer patients and healthy individuals. Hence, this review aimed to assess the possible use of liquid biopsy for cancer diagnosis with piRNAs as biomarkers.

Systematic analysis of tumor transcriptomes, combined with deep genome sequencing and detailed clinical assessment of hundreds of patients, constitutes a powerful strategy aimed to identify potential biomarkers and therapeutic targets to guide personalized treatments. Oncogenic signaling cascades are integrated by multidomain effector proteins such as P-Rex1, a guanine nucleotide exchange factor for the Rac GTPase (RacGEF), known to promote metastatic dissemination of cancer cells. We hypothesized that patients with high P-Rex1 expression and reduced survival might be characterized by a particular set of signaling proteins co-expressed with this effector of cell migration as a central component of a putative signaling hub indicative of poor prognosis. High P-Rex1 expression correlated with reduced survival of TCGA Lower Grade Glioma (LGG) patients. Thus, guided by PREX1 expression, we searched for signaling partners of this RacGEF by applying a systematic unbiased in silico data mining strategy. We identified 30 putative signaling partners that also correlated with reduced patient survival. These included GPCRs such as CXCR3, GPR82, FZD6, as well as MAP3K1, MAP2K3, NEK8, DYRK3 and RPS6KA3 kinases, and PTPN2 and PTPN22 phosphatases, among other transcripts of signaling proteins and phospho-substrates. This PREX1 signaling hub signature correlated with increased risk of shorter survival of LGG patients from independent datasets and coincided with immune and endothelial transcriptomic signatures, indicating that myeloid infiltration and tumor angiogenesis might contribute to worsen brain tumor pathology. In conclusion, P-Rex1 and its putative signaling partners in LGG are indicative of a signaling landscape of the tumor microenvironment that correlates with poor prognosis and might guide the characterization of signaling targets leading the eventual development of immunotherapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is a heterogeneous disease with variable mutational profile and tumour microenvironment composition that influence tumour progression and response to treatment. While chemoresistant and poorly immunogenic CRC remains a challenge, the development of new strategies guided by biomarkers could help stratify and treat patients. Allogeneic NK cell transfer emerges as an alternative against chemoresistant and poorly immunogenic CRC. Methods: NK cell-related immunological markers were analysed by transcriptomics and immunohistochemistry in human CRC samples and correlated with tumour progression and overall survival. The anti-tumour ability of expanded allogeneic NK cells using a protocol combining cytokines and feeder cells was analysed in vitro and in vivo and correlated with CRC mutational status and the expression of ligands for immune checkpoint (IC) receptors regulating NK cell activity. Results: HLA-I downmodulation and NK cell infiltration correlated with better overall survival in patients with a low-stage (II) microsatellite instability-high (MSI-H) CRC, suggesting a role of HLA-I as a prognosis biomarker and a potential benefit of NK cell immunotherapy. Activated allogeneic NK cells were able to eliminate CRC cultures without PD-1 and TIM-3 restriction but were affected by HLA-I expression. In vivo experiments confirmed the efficacy of the therapy against both HLA+ and HLA− CRC cell lines. Concomitant administration of pembrolizumab failed to improve tumour control. Conclusions: Our results reveal an immunological profile of CRC tumours in which immunogenicity (MSI-H) and immune evasion mechanisms (HLA downmodulation) favour NK cell immunosurveillance at early disease stages. Accordingly, we have shown that allogeneic NK cell therapy can target tumours expressing mutations conferring poor prognosis regardless of the expression of T cell-related inhibitory IC ligands. Overall, this study provides a rationale for a new potential basis for CRC stratification and NK cell-based therapy. [ABSTRACT FROM AUTHOR]

In this work, Green Phosphorene (GP) monolayers are studied as an electronic sensing element for detecting prostate cancer biomarkers from human urine. The adsorption of furan, C8H10 (p-xylene), and H2O on pristine GP and S- and Si-doped GP are investigated using the density functional theory (DFT) calculation. Furan and C8H10 molecules have been considered as important biomarkers of prostate cancer patients. First-principles DFT calculations are applied, and the results divulged that pristine GP could be a promising candidate for furan and C8H10 detection. It is manifested that furan and C8H10 are physisorbed on the S-, and Si-doped GP with small adsorption energy and negligible charge transfer. However, the calculations disclose that furan and C8H10 are chemically adsorbed on the pristine GP with adsorption energy of −0.73, and −1.46 eV, respectively. Moreover, we observe that a large charge is transferred from furan to the pristine GP with amount of −0.106 e. Additionally, pristine GP shows short recovery time of 1.81 s at room temperature under the visible light, which make it a reusable sensor device. Overall, our findings propose that the pristine GP sensor is a remarkable candidate for sensing of furan and other biomarkers of prostate cancer in the urine of patients. [ABSTRACT FROM AUTHOR]

Abstract Background Meningiomas are one of the most common tumors of the brain and central nervous system. The key role of endocan in predicting tumor growth and prognosis has been shown for several types of cancers; however, this role in meningiomas has not been evaluated. In the current study, we investigated the relationship between endocan serum levels with low- and high-grade meningiomas. Results The serum level of endocan in the group with meningiomas was 283.34 (242.09-358.70) pg/ml and in the control group was 250.29 (207.56-329.71) pg/ml respectively (P = 0.172). Afterwards, patients were divided into three different groups (grades I, II, and III) and compared to the control. The level of endocan in the group with grade I of meningioma showed no significant difference compared to control individuals (P = 0.86). When patients with grade II and grade III compared with the control group, endocan serum levels were statistically significant (P = 0.002, P < 0.001 respectively). Moreover, our findings showed that the different grades of meningiomas were statistically significant compared to each other (P < 0.001) regarding endocan serum levels, meaning that the higher the grade, the higher the endocan serum levels. Conclusion Our findings revealed that higher grades of meningioma had higher endocan serum levels, however, the role of endocan in pathogenesis or progression of this type of tumor requiring further exclusively assessment.

KIN (Kin17) protein is overexpressed in a number of cancerous cell lines, and is therefore considered a possible cancer biomarker. It is a well-conserved protein across eukaryotes and is ubiquitously expressed in all cell types studied, suggesting an important role in the maintenance of basic cellular function which is yet to be well determined. Early studies on KIN suggested that this nuclear protein plays a role in cellular mechanisms such as DNA replication and/or repair; however, its association with chromatin depends on its methylation state. In order to provide a better understanding of the cellular role of this protein, we investigated its interactome by proximity-dependent biotin identification coupled to mass spectrometry (BioID-MS), used for identification of protein–protein interactions. Our analyses detected interaction with a novel set of proteins and reinforced previous observations linking KIN to factors involved in RNA processing, notably pre-mRNA splicing and ribosome biogenesis. However, little evidence supports that this protein is directly coupled to DNA replication and/or repair processes, as previously suggested. Furthermore, a novel interaction was observed with PRMT7 (protein arginine methyltransferase 7) and we demonstrated that KIN is modified by this enzyme. This interactome analysis indicates that KIN is associated with several cell metabolism functions, and shows for the first time an association with ribosome biogenesis, suggesting that KIN is likely a moonlight protein.

Alcohol dehydrogenase iron containing 1 (ADHFE1) encodes a hydroxyacid-oxoacid transhydrogenase participating in multiple biological processes. The role of ADHFE1 in cancer has not been fully uncovered. Herein, we performed data analysis to investigate the expression of ADHFE1 and the underlying regulatory mechanisms, its relationship with cancer patients’ survival, and the relevant pathways in cancer. A range of recognized, web-available databases and bioinformatics tools were used in this in silico study. We found that ADHFE1 was frequently downregulated and hypermethylated in various cancer cell lines and tissue samples. High expression of ADHFE1 was positively associated with favorable patient prognosis in breast, colon, and gastric cancers. Pathway analysis revealed its potential role in cancer-related biological processes, including energy metabolism, DNA replication, and cell cycle regulation. AHDFE1 mRNA expression and DNA methylation can potentially be used as diagnostic markers in cancer and might be of great value in predicting the survival of patients with cancer.

[Display omitted] • Highly fluorescent GQDs were synthesized using tryptophan as both carbon and nitrogen source. • Ultrasensitive detection of potential cancer biomarker, H 2 O 2 by GQDs in serum medium. • LOD value (61.43 pM) in MCF-7 cell lysate medium. • Inability to sense H 2 O 2 in HaCaT cell lysate medium. Herein, we report a single step synthesis of highly fluorescent Graphene Quantum Dots (GQDs) using tryptophan and glycerol as precursors via pyrolysis. The morphological and functional characterization of the prepared GQDs was performed using PXRD, FTIR, TEM, XPS and zeta potential measurements. The prepared GQDs found their practical application in ultrasensitive detection of an emerging potential cancer biomarker, H 2 O 2 , by exploiting the fluorescence quenching behaviour of H 2 O 2. To evaluate the detection sensitivity, a series of various concentrations of H 2 O 2 was spiked to biomatrices like, serum and MCF-7 (human breast cancer cell line) cell lysate medium. A remarkably low limit of detection (LOD) was found in serum medium (139.5 pM) which further improved in MCF-7 cell lysate medium (LOD 61.43 pM). Moreover, the sensing capacity of the GQDs was further validated in presence of various physiological variables such as glucose, cholesterol, insulin and nitrite. Sensing assay was also carried out in HaCaT (human keratinocyte cell line) cell lysate medium to compare the performance of our prepared sensor but the non-linearity of the F 0 /F versus H 2 O 2 concentration plot pointed towards the conduciveness of the MCF-7 cell lysate medium for sensitive detection of H 2 O 2.The mechanism behind the sensing was also explored using spectroscopic methods. [ABSTRACT FROM AUTHOR]

[Display omitted] • Triangular silver nanoparticles (TA-AgNPs) was synthesized using novel hydrothermal protocol. • TA-AgNPs was used for the identification of cancer biomarkers in human biofluids using smartphone assisted digital image analysis. • A novel photochemical one-drop microarray was proposed for the low-cost sensing of PSA, CEA, CA 15.3 proteins. This system utilizes an innovative platform consisting of a poly (methyl methacrylate) (PMMA) plate adorned with triangular silver nanoparticles, enabling the sensitive and specific detection of prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), and cancer antigen 15–3 (CA 15.3). To achieve this, the PMMA polymer microarrays were precisely cut using a laser cutting machine to create an optimized number of micro-arrays. These designed wells were embellished with triangular silver nanoparticles (TA-AgNPs) featuring prism morphology. The antigens could be easily detected based on antigen–antibody-induced aggregation of TA-AgNPs and resulting in a visible color change due to the alteration of surface plasmon resonance properties. Consequently, utilizing the immunocomplex of antigen–antibody in the presence of the optical probe (TA-AgNPrs) and a portable photochemical sensor, candidate cancer biomarkers (PSA, CEA, and CA 15.3) were successfully identified with linear ranges of 1–60, 1–75, and 1–125 µg/mL, respectively. By employing digital image analysis using a smartphone, we achieved a highly favorable low limit of quantification of 1 µg/mL for PSA, CEA, and CA 15.3 as biomarkers for prostate, colon, and breast cancer, respectively. This groundbreaking research introduces a pioneering digital image-based colorimetry immunoassay, the first of its kind in the field, providing a transformative approach to the early-stage diagnosis of various cancer biomarkers through a single opto-device. To the best of our knowledge, no smartphone ambient light sensor has yet been specifically designed to identify PSA, CEA, and CA 15.3 proteins as cancer biomarkers. Therefore, a sensory micro-array was developed to open new possibilities for the rapid and simple colorimetric identification of PSA, CEA, and CA 15.3 antigens in real samples, offering a sensitive and specific monitoring strategy for these biomarkers through colorimetry. [ABSTRACT FROM AUTHOR]

In this paper, we describe a biosensing instrument based on our previously developed photonic resonator absorption microscope (PRAM) that incorporates autofocus, digital representation of the gold nanoparticle (AuNP) accumulation, and the ability to gather time-series image sequences of AuNP attachment and detachment from the photonic crystal (PC) surface. The combined capabilities are used to fully automate PRAM image collection during biomolecular assays to enable tiling of PRAM images to provide millimeter-scale field of view. The instrument can also gather PRAM "movies" that enables digital showcasing and dynamic counting AuNPs as they arrive and depart from the PC surface. We utilize the capabilities in the context of two biomolecular assays for detection of protein biomarkers in a conventional AuNP-tagged sandwich format. Utilizing dynamic counting of AuNP attachment and detachment events during the assay we present a detection for microRNA-375 (miRNA-375) down to 1 aM with a 10-min, room temperature, enzyme-free approach, while revealing characteristics of the binding-rate and unbinding-rate of the biomolecular interactions. Our instrument can potentially find broad applications in multiplexed point-of-care diagnostic testing, and as a general-purpose tool for quantitative characterization of biomolecular binding kinetics with single-molecule resolution. • Autofocus and millimeter-scale tiled field of view for imaging-based biosensing. • Visualize the accumulation of gold nanoparticles with precise counting algorithm. • Showcases the dynamic and low limit of detection of HIV/HCV antibody and microRNA. • Visualize the thermodynamic process of sandwich and TRAP assay. [ABSTRACT FROM AUTHOR]

Heat shock protein 90 alpha (Hsp90α) is an abundantly expressed and evolutionarily conserved molecular chaperone. Hsp90α is the inducible Hsp90 isoform, and its expression and secretion extracellularly (eHsp90α) can be triggered in response to a variety of cellular stresses to protect/activate client proteins and to facilitate cellular adjustment to the stress. As a result, cancers often have high expression levels of intracellular and extracellular (plasma) Hsp90α, allowing them to support their oncogenesis and progression. In fact, (e)Hsp90α has been implicated in regulating processes such as cell signaling transduction, DNA repair, promotion of the Epithelial-to-Mesenchymal Transition (EMT), promotion of angiogenesis, immune response, and cell migration. Hsp90α levels have been correlated with cancer progression and severity in several cancers, indicating that it may be a useful biomarker or drug-target for cancer. To date, the development of intracellular Hsp90α-targeted therapies include standard N-terminal ATP-competitive inhibitors and allosteric regulators that bind to Hsp90α′s middle or C-terminal domain. On-target toxicities and dosing complications as a result of Hsp90α inhibition has driven the development of eHsp90α-targeted therapies. Examples include anti-Hsp90α monoclonal antibodies and cell-impermeable Hsp90α small molecule inhibitors. This review aims to discuss the many roles Hsp90α plays in cancer progression with a focus on the current development of Hsp90α-targeted therapies. A high-resolution pdf of the graphical abstract has been submitted separately for re-scaling. [Display omitted] • Extracellular heat shock protein 90 alpha implicated as a pan-cancer biomarker. • Therapeutics targeting Hsp90α have been developed with various mechanisms of action. • Extracellular Hsp90α as a target for the treatment of cancer. • Extracellular Hsp90α promotes cancer progression and metastasis. [ABSTRACT FROM AUTHOR]

In the rapidly evolving field of medical diagnostics, biomarkers play a pivotal role, particularly in the early detection of cancer. Cluster of differentiation 5 (CD5), a cell surface glycoprotein found on T cells and B-1a lymphocytes, is instrumental in immune regulation and is associated with both autoimmune diseases and malignancies. Despite its significant diagnostic and therapeutic potential, CD5 detection has been limited by modern methods in the pg/ml range. This study presents a novel multimodal electrochemical immunosensor that employs laser-processed Ti/Au electrodes for the ultra-sensitive detection of CD5 in human blood serum. The "multimodal" approach combines different analytical techniques - differential pulse volctammetry (DPV) and electrochemical impedance spectroscopy (EIS) - to ensure comprehensive analysis, enhancing both the accuracy and reliability of the sensor. This novel sensor significantly outperforms existing commercial ELISA kits, achieving a limit of detection (LOD) of 1.1 ± 0.2 fg/mL with DPV and 3.9 ± 0.5 fg/mL with EIS in phosphate-buffered saline (PBS) and 6.6 ± 3.1 fg/mL and 15.6 ± 3.1 fg/mL in human serum (HS), respectively. These results highlight the immunosensor's potential for improving early-stage cancer diagnosis and broader medical applications. [Display omitted] • Highly sensitive electrochemical multimodal biosensor for CD5 detection. • Outperformed commercial ELISA kits with remarkable LOD. • Demonstrated exceptional selectivity, stability, and performance. • Paved the way for improved disease diagnostics and CD5 research. • Laser-processed Ti/Au electrodes enhance sensor sensitivity. [ABSTRACT FROM AUTHOR]

Systematic analysis of tumor transcriptomes, combined with deep genome sequencing and detailed clinical assessment of hundreds of patients, constitutes a powerful strategy aimed to identify potential biomarkers and therapeutic targets to guide personalized treatments. Oncogenic signaling cascades are integrated by multidomain effector proteins such as P-Rex1, a guanine nucleotide exchange factor for the Rac GTPase (RacGEF), known to promote metastatic dissemination of cancer cells. We hypothesized that patients with high P-Rex1 expression and reduced survival might be characterized by a particular set of signaling proteins co-expressed with this effector of cell migration as a central component of a putative signaling hub indicative of poor prognosis. High P-Rex1 expression correlated with reduced survival of TCGA Lower Grade Glioma (LGG) patients. Thus, guided by PREX1 expression, we searched for signaling partners of this RacGEF by applying a systematic unbiased in silico data mining strategy. We identified 30 putative signaling partners that also correlated with reduced patient survival. These included GPCRs such as CXCR3, GPR82, FZD6, as well as MAP3K1, MAP2K3, NEK8, DYRK3 and RPS6KA3 kinases, and PTPN2 and PTPN22 phosphatases, among other transcripts of signaling proteins and phospho-substrates. This PREX1 signaling hub signature correlated with increased risk of shorter survival of LGG patients from independent datasets and coincided with immune and endothelial transcriptomic signatures, indicating that myeloid infiltration and tumor angiogenesis might contribute to worsen brain tumor pathology. In conclusion, P-Rex1 and its putative signaling partners in LGG are indicative of a signaling landscape of the tumor microenvironment that correlates with poor prognosis and might guide the characterization of signaling targets leading the eventual development of immunotherapeutic strategies.

BackgroundColorectal cancer (CRC) is a heterogeneous disease with variable mutational profile and tumour microenvironment composition that influence tumour progression and response to treatment. While chemoresistant and poorly immunogenic CRC remains a challenge, the development of new strategies guided by biomarkers could help stratify and treat patients. Allogeneic NK cell transfer emerges as an alternative against chemoresistant and poorly immunogenic CRC.MethodsNK cell-related immunological markers were analysed by transcriptomics and immunohistochemistry in human CRC samples and correlated with tumour progression and overall survival. The anti-tumour ability of expanded allogeneic NK cells using a protocol combining cytokines and feeder cells was analysed in vitro and in vivo and correlated with CRC mutational status and the expression of ligands for immune checkpoint (IC) receptors regulating NK cell activity.ResultsHLA-I downmodulation and NK cell infiltration correlated with better overall survival in patients with a low-stage (II) microsatellite instability-high (MSI-H) CRC, suggesting a role of HLA-I as a prognosis biomarker and a potential benefit of NK cell immunotherapy. Activated allogeneic NK cells were able to eliminate CRC cultures without PD-1 and TIM-3 restriction but were affected by HLA-I expression. In vivo experiments confirmed the efficacy of the therapy against both HLA+ and HLA− CRC cell lines. Concomitant administration of pembrolizumab failed to improve tumour control.ConclusionsOur results reveal an immunological profile of CRC tumours in which immunogenicity (MSI-H) and immune evasion mechanisms (HLA downmodulation) favour NK cell immunosurveillance at early disease stages. Accordingly, we have shown that allogeneic NK cell therapy can target tumours expressing mutations conferring poor prognosis regardless of the expression of T cell-related inhibitory IC ligands. Overall, this study provides a rationale for a new potential basis for CRC stratification and NK cell-based therapy.

Abstract Background Various biomarkers are being developed for the early diagnosis of cancer and for predicting its prognosis. The aim of this study is to evaluate the diagnostic significance of serum CD109 in head and neck squamous cell carcinoma (HNSCC). Methods The serum CD109 levels in a total of 112 serum samples collected before and after surgery from 56 HNSCC patients were analyzed with an enzyme‐linked immunosorbent assay (ELISA). The clinical factor that showed a statistically significant association with both the preoperative serum CD109 level, and the CD109 index: which was defined as the ratio of the preoperative serum CD109 level to the postoperative serum CD109 level, were assessed. The correlations between the serum CD109 levels and lymph node density (LND), pathological features such as lymphatic invasion, and serum SCC antigen levels were also assessed. Results The ELISA measurement revealed that preoperative serum CD109 levels were elevated in patients with node metastasis‐positive and stage IV disease, in comparison to those with node metastasis‐negative and Stage I+II+III disease, respectively. A multiple regression analysis indicated that serum CD109 level was significantly associated with the node metastasis status. A Spearman's rank correlation analysis also revealed a positive correlation between the preoperative serum CD109 level and LND. Furthermore, the probabilities of the overall and relapse‐free survival were significantly lower in patients with a preoperative serum CD109 level of ≥38.0 ng/ml and a CD109 index of ≥1.6, respectively, than in others. There was no significant correlation between the serum CD109 and SCC antigen levels. Conclusions The serum CD109 levels were elevated in patients with advanced stage disease, reflecting the node metastasis status. CD109 in sera could be a novel prognostic marker for HNSCC involving lymph node metastasis.

Overexpressed heat shock protein 90 (HSP90) has been proven as a new cancer biomarker, and its detection can be used as an auxiliary diagnosis. In this research, we designed an electrochemical aptasensor to detect this biomarker. Initially, a 3D-printed electrode was designed and produced while the electrode surface (made from a conductive carbon black/ polylactic acid (CB-PLA) filament) was improved by CO 2 laser ablation. Then, the electrode surface was modified with graphene oxide (GO) and an array of frost-like gold nanocrystals (FGNCs); the results showed that the final surface covered with gold contained nano/microstructures with a mean width of ∼ 65 nm and a mean length of ∼ 509 nm. Also, a significant increase in the electrochemically active surface area was observed for modified surfaces with GO and FGNCs. Efficient immobilization of aptamer strands on the gold surface could complete the assembly of this aptasensing platform, which could detect analyte molecules in a linear range from 0.1 to 200 ng mL−1. The estimated limit of detection (LOD) and the limit of quantification (LOQ) were as low as 0.1 ng mL−1 and 0.23 ng mL−1, respectively. The performance of reproducibility (5 times), regeneration (5 times), and stability (7 days) were satisfactory (low relative standard deviation (RSD)). Also, this aptasensor showed adequate performance for selective and accurate analyte capturing in the presence of interfering agents and spiked analyte concentrations in serum samples. • A HSP90 aptasensor has designed based on a nanomaterial-based 3D-printed platform. • The 3D-printed electrode produced using two filaments and improved by laser. • The electrode's surface modified (dual signal amplification) with GO and FGNCs. [ABSTRACT FROM AUTHOR]

Emerging studies demonstrates that mitochondrial G-quadruplex (G4) may be a prospective diagnostic and therapeutic target for cancer. Fluorescent probes targeting mitochondrial G4 are crucial for in-depth research on G4 function and mechanism and developing new diagnostic techniques. Here, we report a benzothiazole derivative named ThT-E, which can be prepared with high yield through only one step of reaction. ThT-E exhibits superior detection sensitivity compared to existing probes, and also demonstrates reliable performance for in situ characterization of mitochondrial G4 in living cells. Interestingly, ThT-E has been used to differentiate tumor cells from normal cells by quantifying the formation of mitochondrial G4s, implicating that ThT-E may have wide applications in tumor diagnosis. • A benzothiazole derivative for monitoring mitochondrial G-quadruplexes. • More pronounced fluorescence enhancement in tumor cells than normal cells. • More G-quadruplex formation in tumor mitochondria. • Mitochondrial G-quadruplex as a potential cancer biomarker. • New probe tool for tumor diagnosis. [ABSTRACT FROM AUTHOR]

In the era of liquid biopsies, the reliable and cost-effective detection and screening of cancer biomarkers has become of fundamental importance, thus paving the way for the advancement of research in the field of point-of-care testing and the development of new methodologies and technologies. Indeed, the latter ones can help designing advanced diagnostic tools that can offer portability, ease of use with affordable production and operating costs. In this respect, impedance-based biosensing platforms might represent an attractive alternative. In this work, we describe a proof-of-concept study aimed at designing portable impedimetric biosensors for the monitoring of human urokinase-type plasminogen activator (h-uPA) cancer biomarker by employing small synthetic receptors. Aberrant levels of h-uPA were correlated with different types of cancers. Herein, we report the use of two bicyclic peptides (P2 and P3) which have been engineered to bind h-uPA with high affinity and exquisite specificity. The synthetic receptors were immobilized via biotin-streptavidin chemistry on the surface of commercial screen-printed electrodes. The impedimetric changes in the electrode/solution interface upon incubation of spiked h-uPA samples in the presence of a redox probe were followed via electrochemical impedance spectroscopy. The P3-based impedimetric assay showed the best outcomes in terms of dynamic range and linearity (0.01–1 μg mL−1) and sensitivity (LOD = 9 ng mL−1). To fully assess the performances of P3 over P2, and to compare the label-free architecture vs. labelled architecture, a voltammetric assay was also developed.

Breast cancer is the second leading cause of cancer deaths in women worldwide; therefore, there is an increased need for the discovery, development, optimization, and quantification of diagnostic biomarkers that can improve the disease diagnosis, prognosis, and therapeutic outcome. Circulating cell-free nucleic acids biomarkers such as microRNAs (miRNAs) and breast cancer susceptibility gene 1 (BRCA1) allow the characterization of the genetic features and screening breast cancer patients. Electrochemical biosensors offer excellent platforms for the detection of breast cancer biomarkers due to their high sensitivity and selectivity, low cost, use of small analyte volumes, and easy miniaturization. In this context, this article provides an exhaustive review concerning the electrochemical methods of characterization and quantification of different miRNAs and BRCA1 breast cancer biomarkers using electrochemical DNA biosensors based on the detection of hybridization events between a DNA or peptide nucleic acid probe and the target nucleic acid sequence. The fabrication approaches, the biosensors architectures, the signal amplification strategies, the detection techniques, and the key performance parameters, such as the linearity range and the limit of detection, were discussed.

Prostate cancer is a disease with a high incidence and mortality rate in men worldwide. Serum prostate-specific antigens (PSA) are the main circulating biomarker for this disease in clinical practices. In this work, we present a portable and reusable microfluidic device for PSA quantification. This device comprises a polymethyl methacrylate microfluidic platform coupled with electrochemical detection. The platinum working microelectrode was positioned in the outflow region of the microchannel and was modified with carbon nanofibers (CNF)-decorated gold nanoporous (GNP) structures by the dynamic hydrogen bubble template method, through the simultaneous electrodeposition of metal precursors in the presence of CNF. CNF/GNP structures exhibit attractive properties, such as a large surface to volume ratio, which increases the antibody’s immobilization capacity and the electroactive area. CNFs/GNP structures were characterized by scanning electron microscopy, energy dispersive spectrometry, and cyclic voltammetry. Anti-PSA antibodies and HRP were employed for the immune-electrochemical reaction. The detection limit for the device was 5 pg mL−1, with a linear range from 0.01 to 50 ng mL−1. The coefficients of variation within and between assays were lower than 4.40%, and 6.15%, respectively. Additionally, its clinical performance was tested in serum from 30 prostate cancer patients. This novel device was a sensitive, selective, portable, and reusable tool for the serological diagnosis and monitoring of prostate cancer.

More than 80% of human cancers originate in epithelial tissues. Loss of epithelial cell characteristics are hallmarks of tumor development. Receptor-mediated endocytosis is a key function of absorptive epithelial cells with importance for cellular and organismal homeostasis. LRP2 (megalin) is the largest known endocytic membrane receptor and is essential for endocytosis of various ligands in specialized epithelia, including the proximal tubules of the kidney, the thyroid gland, and breast glandular epithelium. However, the role and regulation of LRP2 in cancers that arise from these tissues has not been delineated. Here, we examined the expression of LRP2 across 33 cancer types in The Cancer Genome Atlas. As expected, the highest levels of LRP2 were found in cancer types that arise from LRP2-expressing absorptive epithelial cells. However, in a subset of tumors from these cancer types, we observed epigenetic silencing of LRP2. LRP2 expression showed a strong inverse correlation to methylation of a specific CpG site (cg02361027) in the first intron of the LRP2 gene. Interestingly, low expression of LRP2 was associated with poor patient outcome in clear cell renal cell carcinoma, papillary renal cell carcinoma, mesothelioma, papillary thyroid carcinoma, and invasive breast carcinoma. Furthermore, loss of LRP2 expression was associated with dedifferentiated histological and molecular subtypes of these cancers. These observations now motivate further studies on the functional role of LRP2 in tumors of epithelial origin and the potential use of LRP2 as a cancer biomarker.

Cancer is the second leading cause of death worldwide after heart disease. The current treatment options to fight cancer are limited, and there is a critical need for better treatment strategies. During the last several decades, several electric field (EF)-based approaches for anti-cancer therapies have been introduced, such as electroporation and tumor-treating fields; still, they are far from optimal due to their invasive nature, limited efficacy and significant side effects. In this study, we developed a non-contact EF stimulation system to investigate the in vitro effects of a novel EF modality on cancer biomarkers in normal (human astrocytes, human pancreatic ductal epithelial -HDPE-cells) and cancer cell lines (glioblastoma U87-GBM, human pancreatic cancer cfPac-1, and MiaPaCa-2). Our results demonstrate that this EF modality can successfully modulate an important cancer cell biomarker-cell surface phosphatidylserine (PS). Our results further suggest that moderate, but not low, amplitude EF induces p38 mitogen-activated protein kinase (MAPK), actin polymerization, and cell cycle arrest in cancer cell lines. Based on our results, we propose a mechanism for EF-mediated PS exposure in cancer cells, where the magnitude of induced EF on the cell surface can differentially regulate intracellular calcium (Ca2+) levels, thereby modulating surface PS exposure.

The histone lysine methyltransferase DOT1L (DOT1-like histone lysine methyltransferase) is responsible for the epigenetic regulation of gene expression through specific methylation of lysine79 residue of histone H3 (H3K79) in actively transcribed genes. Its normal activity is crucial for embryonic development and adult tissues functions, whereas its aberrant functioning is known to contribute to leukemogenesis. DOT1L is the only lysine methyltransferase that does not contain a SET domain, which is a feature that allowed the development of selective DOT1L inhibitors that are currently investigated in Phase I clinical trials for cancer treatment. Recently, abnormal expression of this enzyme has been associated with poor survival and increased aggressiveness of several solid tumors. In this review evidences of aberrant DOT1L expression and activity in breast, ovarian, prostate, colon, and other solid tumors, and its relationships with biological and clinical behavior of the disease and response to therapies, are summarized. Current knowledge of the structural basis of DOT1L ability to regulate cell proliferation, invasion, plasticity and stemness, cell cycle progression, cell-to-cell signaling, epithelial-to-mesenchymal transition, and chemoresistance, through cooperation with several molecular partners including noncoding RNAs, is also reviewed. Finally, available options for the treatment of therapeutically challenging solid tumors by targeting DOT1L are discussed. [ABSTRACT FROM AUTHOR]

We introduce a digital microfluidics (DMF) platform specifically designed to perform a loop-mediated isothermal amplification (LAMP) of DNA and applied it to a real-time amplification to monitor a cancer biomarker, c-Myc (associated to 40% of all human tumors), using fluorescence microscopy. We demonstrate the full manipulation of the sample and reagents on the DMF platform, resulting in the successful amplification of 90 pg of the target DNA (0.5 ng/µL) in less than one hour. Furthermore, we test the efficiency of an innovative mixing strategy in DMF by employing two mixing methodologies onto the DMF droplets—low frequency AC (alternating current) actuation as well as back-and-forth droplet motion—which allows for improved fluorescence readouts. Fluorophore bleaching effects are minimized through on-chip sample partitioning by DMF processes and sequential droplet irradiation. Finally, LAMP reactions require only 2 µL volume droplets, which represents a 10-fold volume reduction in comparison to benchtop LAMP. [ABSTRACT FROM AUTHOR]

Cancer is a highly fatal disease without effective early-stage diagnosis and proper treatment. Along with the oncoproteins and oncometabolites, several organelles from cancerous cells are also emerging as potential biomarkers. Mitochondria isolated from cancer cells are one such biomarker candidates. Cancerous mitochondria exhibit different profiles compared with normal ones in morphology, genomic, transcriptomic, proteomic and metabolic landscape. Here, the possibilities of exploring such characteristics as potential biomarkers through single-cell omics and Artificial Intelligence (AI) are discussed. Furthermore, the prospects of exploiting the biomarker-based diagnosis and its futuristic utilization through circulatory tumor cell technology are analyzed. A successful alliance of circulatory tumor cell isolation protocols and a single-cell omics platform can emerge as a next-generation diagnosis and personalized treatment procedure. [ABSTRACT FROM AUTHOR]

Nearly 50% of patients recur within two years after curatively intended resection of colorectal cancer liver metastasis (CRLM). The optimal surveillance strategy is unknown due to the lack of evidence. Here, we explored the potential for improving postoperative CRLM surveillance by performing serial circulating tumour DNA (ctDNA) assessments parallel to standard-of-care surveillance. 499 prospectively collected serial plasma samples from 96 patients undergoing CRLM resection were analysed using the tumour-agnostic methylation multiplex droplet-digital PCR test 'TriMeth'. Patients with ctDNA postoperatively or post adjuvant chemotherapy experienced a significant lower recurrence-free survival than patients without ctDNA (hazard ratio (HR) 4.5; P < 0.0001 and HR 8.4, P < 0.0001). ctDNA status was a stronger predictor of recurrence than standard clinical risk factors and carcinoembryonic antigen. Serial TriMeth analysis detected ctDNA before radiological recurrence in 55.6% of ctDNA-positive patients, with up to 10.6 months lead-time (median 3.1 months). During surveillance, 24% of patients had inconclusive CT scans, which was associated with a significant delay in recurrence diagnosis (median 3.5 months versus 1.0 month, P < 0.0001). Uniquely, ctDNA status at the time of inconclusive CT scans predicted recurrence with positive and negative predictive values of 100%, and 75% (P = 0.0003). Serial TriMeth analysis allowed ctDNA growth rate assessment and revealed that fast ctDNA growth was associated with poor overall survival (HR: 1.6, P = 0.0052). Serial postoperative ctDNA analysis has a strong prognostic value and is more sensitive for recurrence detection than standard-of-care CRLM surveillance tools. Altogether, TriMeth provides several opportunities for improving postoperative surveillance of CRLM patients. • Recurrence rates after colorectal cancer liver metastases (CRLM) resection are high. • Postoperative circulating tumour DNA(ctDNA) status is a strong recurrence predictor. • ctDNA analysis at the time of inconclusive surveillance scans predicts recurrence. • Serial analysis detects ctDNA up to 10 months ahead of radiologic recurrence. • ctDNA growth rate as proxy of tumour growth is associated with disease outcome. [ABSTRACT FROM AUTHOR]

Polythionine (PTH) is an electroactive compound known for its excellent electron transfer capacity. It has stable and redox centers in its structure, and it can also be generated by electropolymerization of thionine (TH). Due to its properties, it has been used in a large number of applications, including the construction of electrochemical biosensors. In this work, PTH is explored for its ability to generate electrons, which allows it to act as an electrochemical probe in a biosensor that detects CA 19-9 on two different substrates, carbon and gold, using differential pulse voltammetry (DPV) as a reading technique in phosphate buffer (PhB). The analytical features of the resulting electrodes are given, showing linear ranges from 0.010 to 10 U/mL. The Raman spectra of PTH films on gold (substrates or nanostars) and carbon (substrates) are also presented and discussed as a potential use for SERS readings as complementary information to electrochemical data. [ABSTRACT FROM AUTHOR]

Abstract Cancer is a leading cause of death worldwide, particularly because of its high mortality rate in patients who are diagnosed at late stages. Conventional biomarkers originating from blood are widely used for cancer diagnosis, but their low sensitivity and specificity limit their widespread application in cancer screening among the general population. Currently, emerging studies are exploiting novel, highly-accurate biomarkers in human body fluids that are obtainable through minimally invasive techniques, which is defined as liquid biopsy. Circular RNAs (circRNAs) are a newly discovered class of noncoding RNAs generated mainly by pre-mRNA splicing. Following the rapid development of high-throughput transcriptome analysis techniques, numerous circRNAs have been recognized to exist stably and at high levels in body fluids, including plasma, serum, exosomes, and urine. CircRNA expression patterns exhibit distinctly differences between patients with cancer and healthy controls, suggesting that circRNAs in body fluids potentially represent novel biomarkers for monitoring cancer development and progression. In this study, we summarized the expression of circRNAs in body fluids in a pan-cancer dataset and characterized their clinical applications in liquid biopsy for cancer diagnosis and prognosis. In addition, a user-friendly web interface was developed to visualize each circRNA in fluids ( https://mulongdu.shinyapps.io/circrnas_in_fluids/ ).

Introduction: End-stage renal disease (ESRD) patients are known to have a high risk of developing cancer-related inflammation. Elevated serum levels of tumor markers in ESRD/hemodialysis patients makes analysis and interpretation difficult. Aim: To verify the possible relationship between chronic low-grade systemic inflammation serum levels determined by C-reactive protein (CRP) and the tumor biomarkers in patients on hemodialysis. Materials and methods: A prospective study of prevalence was conducted in the Hemodialysis Sector of the University Hospital of the University of Brasília between July 2016 and December 2016 in men aged 18 to 60 years without clinically detectable cancer. We assessed inflammation by serum high-sensitivity CRP test (hs-CRP) and serum tumor in the case groups and controls. The hemodialysis group was split into two subgroups: group 1: patients with inflammation (CRP > 5 mg/L, n=27), and group 2: patients without inflam-mation (CRP ≤5 mg/L, n=33).Results: There was no significant difference in age mean levels between case groups and controls (44.00±08.00 vs. 41.00±07.00, p=0.08). There was no difference or correlation (p>0.05) between tumor markers levels and patients with and without inflammation. Conclusions: The results of this study suggest that chronic low-grade systemic inflammation defined by C-reactive protein serum levels does not promote elevated serum PSA levels in chronic hemodialysis patients.