Biomarkers For Cancer Screening Research Articles

Association of Hypoxia-Inducible Factor 1α Gene Polymorphisms With Breast Cancer Susceptibility: A Meta-Analysis.

PURPOSEOverexpression of the hypoxia-inducible factor 1α (HIF1A) gene is significantly associated with different types of cancers, including breast cancer. In this study, the effects of single-nucleotide polymorphisms rs11549465, rs11549467, and rs2057482 of the HIF1A gene and their association with breast cancer were systematically investigated through meta-analysis.MATERIALS AND METHODSAfter a systematic review, nine case-control studies of the HIF1A rs11549465 C/T polymorphism, six case-control studies of the HIF1A rs11549467 G/A polymorphism, and one case-control study of the HIF1A rs2057482 C/T polymorphism were included in this meta-analysis. The summary pooled odds ratios with 95% CIs were evaluated to detect the relationship between HIF1A polymorphisms and breast cancer susceptibility.RESULTSSubgroup-stratified analyses showed that the T and TT genotypes of the HIF1A rs11549465 C/T polymorphism were significantly associated with increased breast cancer risk in the Asian population under three genetic models (allele, homozygous, and recessive). HIF1A rs11549467 G/A analyses indicated that the A and AA genotypes were significantly associated with increased breast cancer risk in the Asian population under allele and dominant models. However, no association with breast cancer was observed in the White population for the HIF1A rs11549465 C/T and rs11549467 G/A polymorphisms. In addition, the HIF1A rs2057482 C/T polymorphism showed no association with breast cancer under any genetic models or by ethnicity-stratified analyses.CONCLUSIONThe results of this meta-analysis suggested that the HIF1A rs11549465 C/T and rs1154946 G/A polymorphisms were significantly associated with increased breast cancer risk in the Asian population, but no associations were found in the White population. Thus, HIF1A could be an important biomarker for population-based breast cancer screening.

Combining plasma extracellular vesicle Let-7b-5p, miR-184 and circulating miR-22-3p levels for NSCLC diagnosis and drug resistance prediction

Low-dose computed tomography (LDCT) Non-Small Cell Lung (NSCLC) screening is associated with high false-positive rates, leading to unnecessary expensive and invasive follow ups. There is a need for minimally invasive approaches to improve the accuracy of NSCLC diagnosis. In addition, NSCLC patients harboring sensitizing mutations in epidermal growth factor receptor EGFR (T790M, L578R) are treated with Osimertinib, a potent tyrosine kinase inhibitor (TKI). However, nearly all patients develop TKI resistance. The underlying mechanisms are not fully understood. Plasma extracellular vesicle (EV) and circulating microRNA (miRNA) have been proposed as biomarkers for cancer screening and to inform treatment decisions. However, the identification of highly sensitive and broadly predictive core miRNA signatures remains a challenge. Also, how these systemic and diverse miRNAs impact cancer drug response is not well understood. Using an integrative approach, we examined plasma EV and circulating miRNA isolated from NSCLC patients versus screening controls with a similar risk profile. We found that combining EV (Hsa-miR-184, Let-7b-5p) and circulating (Hsa-miR-22-3p) miRNAs abundance robustly discriminates between NSCLC patients and high-risk cancer-free controls. Further, we found that Hsa-miR-22-3p, Hsa-miR-184, and Let-7b-5p functionally converge on WNT/βcatenin and mTOR/AKT signaling axes, known cancer therapy resistance signals. Targeting Hsa-miR-22-3p and Hsa-miR-184 desensitized EGFR-mutated (T790M, L578R) NSCLC cells to Osimertinib. These findings suggest that the expression levels of circulating hsa-miR-22-3p combined with EV hsa-miR-184 and Let-7b-5p levels potentially define a core biomarker signature for improving the accuracy of NSCLC diagnosis. Importantly, these biomarkers have the potential to enable prospective identification of patients who are at risk of responding poorly to Osimertinib alone but likely to benefit from Osimertinib/AKT blockade combination treatments.

Freezing-assisted nano-sweeping of short oligonucleotides using spherical nucleic acids: A fluorometric platform for quantification of microRNAs

MicroRNAs (miRNAs) have been identified as biomarkers for early cancer screening and diagnosis. As a result, the development of simple methods for quantifying these small RNA species is of great interest. This study describes a new biosensing platform termed nano-sweeping for quantitative detection of miRNA-30a. The sweeping process is driven by a combination of gold nanoparticle-core spherical nucleic acid (AuNP-core SNA) hybridization and gravitational separation. Two modified oligonucleotides, i.e., a capture DNA strand for attachment to the surface of AuNPs and a fluorescent reporter strand for fluorescence signal detection, were designed to be semi-complementary to the miRNA-30a. MiRNA-30a is hybridized with the two semi-complementary oligonucleotides using freezing-assisted hybridization, yielding a three-segment sandwich-type duplex. A centrifugation step causes the nanoparticles to settle, allowing the fluorescent reporter strands involved in sandwich hybridization to coprecipitate with the nanoparticles and be removed from the solution. The decrease in fluorescence intensity of the supernatant is proportional to the miRNA-30a concentration. Calibration curves were constructed using data from both traditional fluorometry and smartphone-based fluorescence imaging. The obtained quantification limit for miRNA-30a was 0.22 and 0.42 ng/µL for fluorometric and smartphone-based calibration models, respectively and a linear response established for the range of 0–3.55 ng/µL. Unlike fluorescence resonance energy transfer (FRET)-based methods, this approach is fluorophore independent, allowing for attachment of any fluorescent dye on the reporter oligonucleotide strand.

Classification of Cervical Cytology Overlapping Cell Images with Transfer Learning Architectures

Cervical cell classification is a clinical biomarker in cervical cancer screening at early stages. An accurate and early diagnosis plays a vital role in preventing the cervical cancer. Recently, transfer learning using deep convolutional neural networks; have been deployed in many biomedical applications. The proposed work aims at applying the cutting edge pre-trained networks: AlexNet, ImageNet and Places365, to cervix images to detect the cancer. These pre-trained networks are fine-tuned and retrained for cervical cancer augmented data with benchmark CERVIX93 dataset available publically. The models were evaluated on performance measures viz; accuracy, precision, sensitivity, specificity, F-Score, MCC and kappa score. The results reflect that the AlexNet model is best for cervical cancer prediction with 99.03% accuracy and 0.98 of kappa coefficient showing a perfect agreement. Finally, the significant success rate makes the AlexNet model a useful assistive tool for radiologist and clinicians to detect the cervical cancer from pap-smear cytology images.

Pre-diagnostic faecal calprotectin levels in patients with colorectal cancer: a retrospective study

BackgroundFaecal calprotectin (FC) is a potential biomarker for colorectal cancer (CRC) screening. There is uncertainty if tumor characteristics are associated with FC levels. We investigated how tumor stage and tumor localization influence the extent of FC levels in patients with CRC in clinical practice.MethodsIn two cohorts of patients with CRC, we retrospectively analyzed FC tests (CALPRO®) performed within three months prior to diagnosis. One hundred twenty-four patients with CRC were included (mean age 68 years, 44% women).ResultsNinety-eight patients with CRC (79%) had a FC ≥ 50 µg/g. FC correlated positively with tumor stage (UICC based on WHO TNM classification) (rs 0.24; p = 0.007) and with CRP levels (rs 0.31, p = 001), and a negatively with B-haemoglobin (rs -0.21; p = 0.019). The patients with right-sided CRC had significantly more often a FC ≥ 50 µg/g than patients with left-sided CRC (92% vs 74% p = 0.027). In a binary logistic regression analysis, tumor stage III/IV (adjusted OR 3.47; CI 1.27–9.42) and right-sided tumor localization (adjusted OR 3.80; CI 1.01–14.3) were associated with FC ≥ 50 µg/g. Tumor stage III/IV (adjusted OR 2.30; CI 1.04–5.10) and acetylsalicylic use (adjusted OR 3.54; CI 1.03–12.2) were associated with FC ≥ 100 µg/g. In a cox regression analysis, a FC ≥ 100 µg/g was not associated with survival (Hazard OR 0.61; CI 0.24–1.52).ConclusionsElevated pre-diagnostic FC levels were common in patients with CRC in close proximity to diagnosis. Right-sided localization and tumor stage were significantly associated with a rise in FC levels.

Impedimetric sensing platform for human papillomavirus and p53 tumor suppressor gene in cervical samples

The oncogenic human papillomavirus (HPV) is an excellent biomarker for cervical cancer screening. The present research reports the construction of an integrated sensor platform (biosensor MY11 and biosensor p53 ) for the impedimetric detection of the HPV L1 sequence and p53 tumor suppressor gene. The nanostructured biosensor is composed of electrosynthesized polypyrrole (PPy) and gold nanoparticles (AuNPs). Methodological strategies based on cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), and atomic force microscopy (AFM) were used. The exposure of the genetic biosensors to molecular targets triggered changes in the analytical signals. Calibration plots for the biosensor MY11 showed a linear range between 0.001 to 100 pg μL −1 for all analyzed genotypes (HPV6, 11, 16, 18, 45, 53, 54, and 58). The detection limits were measured between 0.11 to 0.61 pg μL −1 and limits of quantification between 0.33 to 1.86 pg μL −1 . The sensors exhibited reproducibility with a relative standard deviation of 4.21% and high repeatability (less than 2.5%). Two electrochemical profiles were obtained for high and low-risk HPV groups, suggesting the differential diagnosis using a degenerate oligonucleotide probe. Our results allow correlating the p53 gene expression in clinical samples infected with papillomavirus. The proposed biosensor represents an innovative device for the integrated monitoring of biomarkers related to cervical cancer with ultra-sensitive analytical performance. • A nanointegrated system was designed for the differential diagnosis of papillomavirus. • Polypyrrole conjugated to gold particles acted as an ultrasensitive signal transducer. • High and low-risk HPV groups were identified using a degenerate oligonucleotide probe. • Molecular screening for oncogenic HPV and p53 gene was performed in clinical samples. • The biosensor showed high specificity with a linear range from 0.001 to 100 pg μL −1 .

An Electrochemical and Raman Scattering Dual Detection Biosensor for Rapid Screening and Biomolecular Profiling of Cancer Biomarkers

Detecting circulating biomarkers sensitively and quantitatively is paramount for cancer screening, diagnosis, and treatment selection. Particularly, screening of a panel of circulating protein biomarkers followed by mapping of individual biomarkers could assist better diagnosis and understanding of the cancer progression mechanisms. Herein, we present a miniaturized biosensing platform with dual readout schemes (electrochemical and Surface enhanced Raman scattering (SERS)) for rapid cancer screening and specific biomarker expressional profiling to support cancer management. Our approach utilizes a controlled nanomixing phenomena under alternative current electrohydrodynamic condition to improve the isolation of cancer-associated circulating proteins (i.e., Epidermal growth factor receptor (EGFR), BRAF, Programmed death-ligand 1 (PD-L1)) with antibody functionalized sensor surface for rapid and efficient isolation of the targets and subsequent labelling with SERS nanotags. The method employs Differential Pulse Voltammetry (DPV) for rapidly screening for the presence of the circulating proteins on biosensor surface irrespective of their type. Upon positive DPV detection, SERS is applied for sensitive read-out of individual biomarkers biomarker levels. In a proof-of-concept study, we demonstrate the dual detection biosensor for analysing circulating BRAF, EGFR and PDL-1 proteins and successfully screened both ensemble and individual biomarker expressional levels as low as 10 pg (1 ng/mL). Our findings clearly indicate the potential of the proposed method for cancer biomarker analysis which may drive the translation of this dual sensing concept in clinical settings.

Evaluation of fecal SYPL1 as a diagnostic biomarker in colorectal cancer

BackgroundAt present, there is still no ideal non-invasive biomarker for colorectal cancer (CRC) screening. Previously, we foundserum synaptophysin like 1 (SYPL1) served as a potential biomarker for CRC diagnosis. However, whether fecal SYPL1 (fSYPL1) are more sensitive and specific for CRC remains unclear. MethodsWe analyzed fSYPL1 in controls (n = 70), adenoma patients (n = 80), CRC patients (n = 150) and postoperative CRC patients (n = 25) by ELISA. ResultsSYPL1 was stable in feces. The fSYPL1 levels were significantly higher in CRC patients than in either controls or adenoma patients (P < 0.0001). ROC curves showed that fSYPL1 performed superbly in distinguishing CRC patients from controls (AUC = 0.947; 95% CI: 0.920–0.974, P < 0.0001, sensitivity: 80.67%, specificity: 100.00%), which showed much stronger performance than the traditional biomarkers (FOBT, CEA and CA19-9). Meanwhile, the fSYPL1 level positively correlated with tumor size, tumor invasion, lymph node invasion and clinical stage (P < 0.05). In addition, the detection rate of fSYPL1 was high in early CRC (75.00% in stage I and II). The fSYPL1 levels in CRC patients declined substantially after surgery (P = 0.0002). By means of a lower cut off level, 73.58% of high-risk adenomas were detected. The combination of fSYPL1 and FOBT performed better than the combination of plasma SYPL1, CEA and CA199 in distinguishing CRC patients from controls. ConclusionThe fSYPL1 might be a potential biomarker for CRC screening, early diagnosis, prognosis prediction and therapeutic effect monitoring.

Prediction of occult tumor progression via platelet RNAs in a mouse melanoma model: a potential new platform for early detection of cancer

BackgroundCancer screening provides the opportunity to detect cancer early, ideally before symptom onset and metastasis, and offers an increased opportunity for a better prognosis. The ideal biomarkers for cancer screening should discriminate individuals who have not developed invasive cancer yet but are destined to do so from healthy subjects. However, most cancers lack effective screening recommendations. Therefore, further studies on novel screening strategies are urgently required.MethodsWe used a simple suboptimal inoculation melanoma mouse model to obtain ‘pre-diagnostic samples’ of mice with macroscopic melanomas. High-throughput sequencing and bioinformatic analysis were employed to identify differentially expressed RNAs in platelet signatures of mice injected with a suboptimal number of melanoma cells (eDEGs) compared with mice with macroscopic melanomas and negative controls. Moreover, 36 genes selected from the eDEGs via bioinformatics analysis were verified in a mouse validation cohort via quantitative real-time PCR. LASSO regression was utilized to generate the prediction models with gene expression signatures as the best predictors for occult tumor progression in mice.ResultsThese RNAs identified from eDEGs of mice injected with a suboptimal number of cancer cells were strongly enriched in pathways related to immune response and regulation. The prediction models generated by 36 gene qPCR verification data showed great diagnostic efficacy and predictive value in our murine validation cohort, and could discriminate mice with occult tumors from control group (area under curve (AUC) of 0.935 (training data) and 0.912 (testing data)) (gene signature including Cd19, Cdkn1a, S100a9, Tap1, and Tnfrsf1b) and also from macroscopic tumor group (AUC of 0.920 (training data) and 0.936 (testing data)) (gene signature including Ccr7, Cd4, Kmt2d, and Ly6e).ConclusionsOur proof-of-concept study provides evidence for potential clinical relevance of blood platelets as a platform for liquid biopsy-based early detection of cancer.

Molecular Profiling of Liquid Biopsies for Precision Oncology.

In recent years, the rapid development of next-generation sequencing (NGS) has led to a significant increase in accuracy toward molecular profiling, allowing noninvasive and real-time detection of novel biomarkers for cancer screening and dynamic monitoring of disease development. Currently, the biggest challenge liquid biopsies face is the selection of the highest signal-bearing tissues (blood/urine or others) and components for diagnosis, being either circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), or extracellular vesicles (EVs). This chapter describes the process of identifying cancer-associated molecular signals from liquid biopsies. First, we address strategies in selecting and processing samples for sequencing, and technical considerations involved in liquid biopsies under three settings: early detection, cancer diagnosis, and metastatic monitoring. Next, we discuss the methods and challenges to identify and validate prognostic signals, such as tumor burden or stage from CTC, targeted and nontargeted mutations from ctDNA, or noncoding RNAs from EVs. Finally, we review the current landscape of novel biomarkers and ongoing clinical trials for liquid biopsies to discuss the potential avenues for future precision medicine and clinical implementation.

Serum pepsinogen level as a biomarker for atrophy, reflux esophagitis, and gastric cancer screening in Indonesia.

Chronic dyspepsia's symptoms are frequently seen in primary to tertiary healthcare in Indonesia. This study aimed to describe the potential usability of pepsinogen (PG) values in determining gastric mucosal conditions, including superficial gastritis and atrophic gastritis. We recruited 646 adult dyspeptic patients and then analyzed PG values (including PGI, PGII, and PGI/II ratio) with endoscopic findings, gastric mucosal damages, and Helicobacter pylori infection. The gastric mucosal damage and H. pylori infection were evaluated using histological examination based on the updated Sydney system. Among 646 enrolled patients, 308 (47.2%), 212 (32.8%), 91 (14.1%), 34 (5.2%), and 1 (0.2%) patient were diagnosed with normal mucosa, gastritis, reflux esophagitis, peptic ulcer disease, and gastric cancer, respectively. Significant differences in PGI, PGII, and PGI/II ratio values were observed among ethnic groups (all P < 0.01). The PGI and PGII levels were significantly higher and PGI/II was significantly lower in H. pylori-infected patients than in uninfected ones (all P < 0.001). The optimal cutoff value for PGII and PGI/II was 12.45 ng/mL with an area under the curve (AUC) value of 0.755 (0.702-0.811), sensitivity 59.3%, and specificity 77.1%; and 4.75 with AUC value of 0.821 (0.763-0.855), sensitivity 81.5%, and specificity 78.7%, respectively, to determine moderate-severe atrophy. Serum PG levels, a useful biomarker, represent the endoscopic findings, especially for reflux esophagitis. In addition, the benefits of PG values detecting atrophic gastritis were limited to moderate-severe atrophic gastritis. This usefulness requires careful attention for several ethnic groups in Indonesia.

Abstract PR-16: Serum prostate-specific antigen levels and prostate cancer risk in a multiethnic population

Abstract Purpose: While prostate-specific antigen (PSA) is the most commonly used biomarker for prostate cancer (PCa) screening, multiple studies in the U.S. and Europe have shown that PSA levels in midlife, many years before a PCa diagnosis, are associated with increased risk of PCa later in life. However, limited information is available on the relationship between PSA levels measured years before diagnosis and risk of PCa in non-White populations. Methods: We examined whether a PSA level in older adult men measured up to 10+ years before a PCa diagnosis is associated with risk of overall PCa and aggressive PCa (Gleason score&amp;gt;7, non-localized disease, or death from PCa) in a nested case-control study of African American (AA), Latino (LA), Japanese (JP), Native Hawaiian (NH), and Non-Hispanic White (WH) men in the Multiethnic Cohort (MEC). Pre-diagnostic blood levels of total PSA were measured among 2,245 incident PCa cases and 2,203 age and ancestry matched controls. We also assessed the discriminative ability of PSA, years before diagnosis, relative to a polygenic risk score (PRS) for PCa. Results: The mean age at blood draw when PSA was measured for cases and controls was 68 (range: 47-86) and 69 (47-87), respectively. Among cases, the average duration between blood draw and a PCa diagnosis was 4.9 years (range: &amp;lt;1 year to 18 years). Compared to men with PSA below the median, men with PSA above the median had odds ratios (ORs) (95% CIs) for total PCa of 26.15 (16.73-40.87), 7.56 (5.60-10.22) and 3.67 (2.40-5.61), when measured &amp;lt;5, 5-10, and 10+ years before a PCa diagnosis, respectively. The magnitude of the associations were similar for aggressive disease. In men with PSA measured &amp;lt;5, 5-10 and 10+ years before a diagnosis, 95%, 89% and 75% of total PCa cases, respectively, were found to occur among men with a PSA level above the median, while 58%, 28% and 19% of cases, respectively, occurred among men with a PSA level in the top 10th percentile. By race/ethnicity group, the percentages of cases occurred among men with a PSA level above the median measured &amp;lt;5, 5-10 and 10+ years before a diagnosis were: 98%, 89%, 76% in AA; 93%, 90%, 80% in LA; 95%, 91%, 80% in JP; 96%, 95%, 69% in NH, and; 95%, 82%, 65% in WH, respectively. In analysis of the PRS, 25% of cases occurred among those in the top 10th percentile of the PRS distribution. At 10+ years, the independent effect of PSA on total PCa (OR per SD increase: 1.88, CI: 1.45-2.46) was comparable to the independent effect of the PRS (OR per SD increase: 2.12, CI: 1.55-2.93) in a model that mutually adjusted the effects of both PSA and PRS. Conclusions: Our findings in this study among older men suggest that PSA is informative as a marker of risk within 10 years of diagnosis, whereas the PRS can be used to define a man's risk earlier in life. Citation Format: Alisha Chou, Burcu F. Darst, Lynne R. Wilkens, Loïc Le Marchand, Hans G. Lilja, David V. Conti, Christopher A. Haiman. Serum prostate-specific antigen levels and prostate cancer risk in a multiethnic population [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PR-16.

Nanopore Detection of Cancer Biomarkers: A Challenge to Science.

Cancer is the most complex and leading cause of fatality worldwide. Despite meritorious research in the field of cancer, it is still a substantial threat to human life. In this article, we address a question on the present strategies and manifest the importance of critical biomarkers for cancer screening and early diagnosis before the symptoms appear. However, this goal can only be achieved if scientists will focus on ultra-sensitive detection techniques such as “Nanopore.” Nanopore sensing is a simple and rapid single-molecule detection technique that can detect multiple cancer biomarkers in femto-Molar concentrations in real time. Last but not least, we propose a systematic policy to win the war against cancer that is a big challenge to science.

Bladder cancer biomarker screening based on non-targeted urine metabolomics.

Bladder cancer is one of the most common malignancies of the urinary system, and its screening relies heavily on invasive cystoscopy, which increases the risk of urethral injury and infection. This study aims to use non-targeted metabolomics methods to screen for metabolites that are significantly different between the urine of bladder cancer patients and cancer-free controls. In this study, liquid chromatography-mass spectrometry was used to analyze the urine of bladder cancer patients (n = 57) and the cancer-free controls (n = 38) by non-targeted metabolomic analysis and metabolite identification. The results showed that there were significant differences in the expression of 27 metabolites between bladder cancer patients and the cancer-free controls. In the multivariate statistical analysis of this study, the urinary metabolic profile data of bladder cancer patients were analyzed, and the receiver operating characteristic curve analysis showed that it is possible to perform non-invasive clinical diagnoses of bladder cancer through these candidate biomarkers.

A Compact Surface Plasmon Resonance Biosensor for Sensitive Detection of Exosomal Proteins for Cancer Diagnosis.

Exosomes are nanosized (50-150nm) extracellular vesicles released by all types of cells in the body. They transport various biological molecules, such as DNAs, RNAs, proteins, and lipids from parent cells to recipient cells for intercellular communication. Exosomes, especially those from tumor cells, are actively involved in caner development, metastasis, and drug resistance. Recently, many studies have shown that exosomal proteins are promising biomarkers for cancer screening, early detection and prognosis. Among many detection techniques, surface plasmon resonance (SPR) is a highly sensitive, label-free, and real-time optical detection method. Commercial prism-based wavelength/angular-modulated SPR sensors afford high sensitivity and resolution, but their large footprint and high cost limit their adaptability for clinical settings. We have developed an intensity-modulated, compact SPR biosensor (25cm×10cm×25cm) for the detection of exosomal proteins. We have demonstrated the potential application of the compact SPR biosensor in lung cancer diagnosis using exosomal epidermal growth factor receptor (EGFR) and programmed death-ligand 1 (PD-L1) as biomarkers. The compact SPR biosensor offers sensitive, simple, fast, user-friendly, and cost-effective detection of exosomal proteins, which may serve as an in vitro diagnostic test for cancer.

Development of an Efficient Immunosensing Platform by Exploring Single-Walled Carbon Nanohorns (SWCNHs) and Nitrogen Doped Graphene Quantum Dot (N-GQD) Nanocomposite for Early Detection of Cancer Biomarker.

In this work, a novel electrochemical immunosensor based on nitrogen doped graphene quantum dot (N-GQD) and single-walled carbon nanohorns (SWCNHs) was developed for the detection of α-fetoprotein (AFP), a cancer biomarker. Thus, to fabricate the platform of the immunosensor, nanocomposite architecture was developed by decorating N-GQD on the surface of the SWCNHs. The resulting hybrid architecture (N-GQD@SWCNHs) functioned as an exceptional base for the immobilization of antibody (Anti-AFP) through carbodiimide reaction with good stability and bioactivity. The immunosensor was prepared by evenly distributing the bioconjugates (N-GQD@SWCNHs/Anti-AFP) dispersion on the surface of the glassy carbon electrode, and subsequently blocking the remaining active sites by bovine serum albumin to prevent the nonspecific adsorption. Cyclic voltammetry and electrochemical impedance spectroscopy technique was employed to investigate the assembly process of the immunosensor. Under optimal conditions, the immunosensor exhibited a broad dynamic range in between 0.001 ng/mL to 200 ng/mL and a low detection limit of 0.25 pg/mL. Furthermore, the sensor showed high selectivity, desirable stability, and reproducibility. Measurements of AFP in human serum gave outstanding recovery within 99.2% and 102.1%. Thus, this investigation and the amplification strategy exhibited a potential role of the developed nanocomposite based sensor for early clinical screening of cancer biomarkers.

A dual-modal aptasensor based on a multifunctional acridone derivate for exosomes detection

Exosomes are promising biomarkers for cancer screening, but the development of a robust approach that can sensitively and accurately detect exosomes remains challenging. In the present study, an aptasensor based on the multifunctional signal probe 10-benzyl-2-amino-acridone (BAA) was developed for the colorimetric and photoelectrochemical detection and quantitation of exosomes. Exosomes are captured by cholesterol DNA anchor-modified magnetic beads (MBs) through hydrophobic interactions. This capture process can be monitored under a confocal fluorescence microscope using BAA as the fluorescent signal probe. The aptamer modified copper oxide nanoparticles (CuO NPs) then bind to mucin 1 (MUC1) on the surface of the exosomes to form a sandwich structure (MBs-Exo-CuO NPs). Finally, the MBs-Exo-CuO NPs are dissolved in nitric acid to generate Cu2+, which inhibits the visible-light-induced oxidase mimic activity and photoelectrochemical activity of BAA simultaneously. The changes in absorbance and photocurrent intensities are directly proportional to the concentration of exosomes. In this dual-modal aptasensor, the colorimetric assay can achieve rapid screening and identification, which is especially useful for point-of-care testing. The UV–vis absorbance and photocurrent assays then provide quantitative information, with a limit of detection of 1.09 × 103 particles μL−1 and 1.38 × 103 particles μL−1, respectively. The proposed aptasensor thus performs dual-modal detection and quantitation of exosomes. This aptasensor provides a much-needed toolset for exploring the biological roles of exosomes in specific diseases, particularly in the clinical setting.

Regulation of CDK inhibitor p27 by microRNA 222 in breast cancer patients

BackgroundBreast cancer is the most common of all cancers and the second leading cause of cancer-related deaths among women worldwide. MicroRNAs regulate at least 60% of the human genes, including tumor suppressor genes and oncogenes, and can thereby affect cancer risk. In this study, the prognostic values of the CDK inhibitor p27 and miR-222 as biomarkers for breast cancer were evaluated. MethodsThe real-time quantitative polymerase chain reaction method was employed to measure the expression level of miR-222, whereas the serum levels of the CDK inhibitor p27 were measured via enzyme-linked immunosorbent assay. The levels were determined in sera from 110 participants representing three different groups. ResultsPatients with breast cancer exhibited significantly higher expression levels of miR-222 and lower levels of CDK inhibitor p27 than the control group. In addition, a statistically significant inverse correlation between miR-222 and the CDK inhibitor p27 was observed. The receiver operating characteristic curves plotted for serum p27 and miR-222 helped in significantly differentiating between breast cancer patients and controls but could not discriminate between those with stage II and stage III cancer. ConclusionThus, a significant upregulation in the serum miR-222 levels was observed in cancer patients, and a significant inverse correlation was noted between the miR-222 and CDK inhibitor p27 expression levels. These findings indicate that miR-222 may be used as a useful noninvasive screening biomarker for human breast cancer. MicroabstractNovel biomarkers for prognosis, prediction, and therapeutic purposes are essential as the prognosis and therapeutic targets of breast cancer are dependent on traditional markers, such as the tumor stage and hormonal receptor status. This study aimed to evaluate the diagnostic and prognostic values of the CDK inhibitor p27 and miR-222 in breast cancer. Our results indicated that miR-222 and the CDK inhibitor p27 may be used as noninvasive biomarkers to screen for human breast cancer but cannot discriminate between patients with early breast cancer and patients with advanced breast cancer.

Cyclomodulins and Hemolysis in E. coli as Potential Low-Cost Non-Invasive Biomarkers for Colorectal Cancer Screening.

The frequent occurrence of E. coli positive for cyclomodulins such as colibactin (CLB), the cytotoxic necrotizing factor (CNF), and the cytolethal distending factor (CDT) in colorectal cancer (CRC) patients published so far provides the opportunity to use them as CRC screening markers. We examined the practicability and performance of a low-cost detection approach that relied on culture followed by simplified DNA extraction and PCR in E. coli isolates recovered from 130 CRC patients and 111 controls. Our results showed a statistically significant association between CRC and the presence of colibactin genes clbB and clbN, the cnf gene, and newly, the hemolytic phenotype of E. coli isolates. We also observed a significant increase in the mean number of morphologically distinct E. coli isolates per patient in the CRC cohort compared to controls, indicating that the cyclomodulin-producing E. coli strains may represent potentially preventable harmful newcomers in CRC patients. A colibactin gene assay showed the highest detection rate (45.4%), and males would benefit from the screening more than females. However, because of the high number of false positives, practical use of this marker must be explored. In our opinion, it may serve as an auxiliary marker to increase the specificity and/or sensitivity of the well-established fecal immunochemical test (FIT) in CRC screening.

Biomarkers for Gastric Cancer Screening and Early Diagnosis.

Gastric cancer is one of the most common cancers worldwide, with a bad prognosis associated with late-stage diagnosis, significantly decreasing the overall survival. This highlights the importance of early detection to improve the clinical course of these patients. Although screening programs, based on endoscopic or radiologic approaches, have been useful in countries with high incidence, they are not cost-effective in low-incidence populations as a massive screening strategy. Additionally, current biomarkers used in daily routine are not specific and sensitive enough, and most of them are obtained invasively. Thus, it is imperative to discover new noninvasive biomarkers able to diagnose early-stage gastric cancer. In this context, liquid biopsy is a promising strategy. In this review, we briefly discuss some of the potential biomarkers for gastric cancer screening and diagnosis identified in blood, saliva, urine, stool, and gastric juice.