Biomarkers For Detection Of Cancer Research Articles

Emerging Biohybrids of Aptamer-Based Nano-Biosensing Technologies for Effective Early Cancer Detection.

Cancer is a leading global cause of mortality, which underscores the imperative of early detection for improved patient outcomes. Biorecognition molecules, especially aptamers, have emerged as highly effective tools for early and accurate cancer cell identification. Aptamers, with superior versatility in synthesis and modification, offer enhanced binding specificity and stability compared with conventional antibodies. Hence, this article reviews diagnostic strategies employing aptamer-based biohybrid nano-biosensing technologies, focusing on their utility in detecting cancer biomarkers and abnormal cells. Recent developments include the synthesis of nano-aptamers using diverse nanomaterials, such as metallic nanoparticles, metal oxide nanoparticles, carbon-derived substances, and biohybrid nanostructures. The integration of these nanomaterials with aptamers significantly enhances sensitivity and specificity, promising innovative and efficient approaches for cancer diagnosis. This convergence of nanotechnology with aptamer research holds the potential to revolutionize cancer treatment through rapid, accurate, and non-invasive diagnostic methods.

MicroRNAs: circulating biomarkers for the early detection of imperceptible cancers via biosensor and machine-learning advances.

This review explores the topic of microRNAs (miRNAs) for improved early detection of imperceptible cancers, with potential to advance precision medicine and improve patient outcomes. Historical research exploring miRNA's role in cancer detection collectively revealed initial hurdles in identifying specific miRNA signatures for early-stage and difficult-to-detect cancers. Early studies faced challenges in establishing robust biomarker panels and overcoming the heterogeneity of cancer types. Despite this, recent developments have supported the potential of miRNAs as sensitive and specific biomarkers for early cancer detection as well as having demonstrated remarkable potential as diagnostic tools for imperceptible cancers, such as those with elusive symptoms or challenging diagnostic criteria. This review discusses the advent of high-throughput technologies that have enabled comprehensive detection and profiling of unique miRNA signatures associated with early-stage cancers. Furthermore, advancements in bioinformatics and machine-learning techniques are considered, exploring the integration of multi-omics data which have potential to enhance both the accuracy and reliability of miRNA-based cancer detection assays. Finally, perspectives on the continuing development on technologies as well as discussion around challenges that remain, such as the need for standardised protocols and addressing the complex interplay of miRNAs in cancer biology are conferred.

Differences in baseline ctDNA value between Hispanic and non-Hispanic White patients with soft tissue sarcoma (STS): A single-center retrospective analysis.

e23533 Background: Circulating tumor DNA (ctDNA) has shown promise as a biomarker for cancer detection and tracking in multiple malignancies like melanoma, colon and lung. Due to the heterogeneity of sarcoma, there has been limited research on ctDNA as a tool for measuring minimal residual disease (MRD). Differences in baseline in ctDNA for STS in racial minorities have been poorly studied. To identify potential racial differences in the efficacy of this tool, this study compares the quantitative values of baseline ctDNA between non-Hispanic white (NHW) and Hispanic (H) patients with soft tissue sarcoma (STS). Methods: The medical records of 33 STS patients who had ctDNA analysis from Natera™ were examined retrospectively at Dignity Health Cancer Institute.There were 19 H patients and 14 NHW patients in the group. All Black (B), Asian (A), and Other (O) racial groups were excluded due to lower numbers. GraphPad Prism software was used to examine the baseline ctDNA levels. Using continuous measures for statistical analysis, we conducted descriptive statistics and determined the mean, standard deviation, and median ctDNA levels for each group. The ctDNA levels were compared between groups using a two-tailed t-test with a significance level of p < 0.05. Results: The average ctDNA levels were 416.675 (standard deviation = 1349.394) in NHW and 300.305 (standard deviation = 1000.543) in H. The median levels were 0 for both groups. The statistical analysis showed that there was no significant differences in the baseline ctDNA levels between the two groups (p = 0.73). Furthermore, the gender distribution among NHW and Hs in the cohort was comparable, with a p-value of 1.00. Conclusions: This study establishes that there is no substantial differences in baseline levels of ctDNA between H and NHW patients with STS. These findings indicate that ctDNA levels in these populations can be equally utilized for diagnostic and monitoring reasons in clinical settings. Nevertheless, to gain a comprehensive understanding of the racial disparities in ctDNA utility and its implications in customized treatment for STS, it is necessary to conduct more extensive research with larger sample sizes and incorporate additional variables.

Can Tumour Antigens Act as Biomarkers for the Early Detection of Non-Small Cell Lung Cancer?

Lung cancer (LC) is one of the leading causes of cancer-related deaths. Pulmonary nodules are one of the risk factors, and their discovery rate has been increasing due to enhanced performance of chest CT scans, but more than 90% are non-malignant, causing unnecessary stress to patients and costs to healthcare providers. Early diagnosis of LC is associated with a 5-year survival rate of up to 75% following surgical resection, but LC is often diagnosed late due to a lack of symptoms and poor 5-year survival rates as low as 10%. The cost of LC diagnosis is high, with 40% of it associated with benign lesions, which are difficult to differentiate from malignant lesions. Tumour-associated antigens (TAAs) may provide one way in which LC could be diagnosed early using minimally-invasive techniques, under their association with immune responses and specificity for disease. Here we discuss the potential of cancer-testis antigens (CTAs) to act as non-invasive biomarkers for the early detection of non-small cell lung cancer.

Triple-Negative Breast Cancer EVs Modulate Growth and Migration of Normal Epithelial Lung Cells.

Breast cancer is the most common cancer amongst women worldwide. Recently, owing to screening programs and new technologies, the survival rate has increased significantly. Breast cancer can potentially develop metastases, and, despite them, lung metastases generally occur within five years of breast cancer diagnosis. In this study, the objective was to analyze the effect of breast cancer-derived EVs on a lung epithelial cell line. BEAS-2B cells were treated with extracellular vesicles (EVs) derived from triple-negative breast cancer cells (TNBCs), e.g., MDA-MB-231 and HS578T, separated using differential ultracentrifugation. We observed an increased growth, migration, and invasiveness of normal epithelial lung cells over time in the presence of TNBC EVs compared to the control. Therefore, these data suggest that EVs released by tumor cells contain biological molecules capable of influencing the pro-tumorigenic activity of normal cells. Exploring the role of EVs in oncology research and their potential cargo may be novel biomarkers for early cancer detection and further diagnosis.

Development of Ti3C2Tx‐based novel immunosensor for cancer biomarker detection

In this study, an ultrasensitive label‐free electrochemical immunosensor based on Ti3C2Tx (Mxene) with a 2D‐layered morphology has been proposed for the detection of EpCAM antigen. A hydrothermal method is employed for the synthesis of Ti3C2Tx by using a less toxic exfoliating reagent, NaBF4. The bioelectrode, BSA/anti‐EpCAM/Ti3C2Tx@ITO, has been fabricated by electrophoretic deposition of Ti3C2Tx onto the ITO electrode, followed by an immobilization of EpCAM antibody. Electrochemical response studies reveal that the immunosensor shows a high sensitivity of 29.22 μA fg−1 ml cm−2 and a wide linear range from 0.1 fg/ml to 100 ng/ml, for EpCAM antigen detection. Further, the good stability of this fabricated immunosensor is an additional advantage for EpCAM antigen detection in serum samples.

CCDC12 gene methylation in peripheral blood as a potential biomarker for breast cancer detection

Background Aberrant DNA methylation has been identified as biomarkers for breast cancer detection. Coiled-coil domain containing 12 gene (CCDC12) implicated in tumorigenesis. This study aims to investigate the potential of blood-based CCDC12 methylation for breast cancer detection. Methods DNA methylation level of CpG sites (Cytosine-phosphate Guanine dinucleotides) in CCDC12 gene was measured by mass spectrometry in 255 breast cancer patients, 155 patients with benign breast nodules and 302 healthy controls. The association between CCDC12 methylation and breast cancer risk was evaluated by logistic regression and receiver operating characteristic curve analysis. Results A total of eleven CpG sites were analyzed. The CCDC12 methylation levels were higher in breast cancer patients. Compared to the lowest tertile of methylation level in CpG_6,7, CpG_10 and CpG_11, the highest quartile was associated with 82, 91 and 95% increased breast cancer risk, respectively. The CCDC12 methylation levels were associated with estrogen receptor (ER) and human epidermal growth factor 2 (HER2) status. In ER-negative and HER2-positive (ER-/HER2+) breast cancer subtype, the combination of four sites CpG_2, CpG_5, CpG_6,7 and CpG_11 methylation levels could distinguish ER−/HER2+ breast cancer from the controls (AUC = 0.727). Conclusion The hypermethylation levels of CCDC12 in peripheral blood could be used for breast cancer detection.

Hypersensitive detection of CYFRA21-1 by SERS dual antibody sandwich method

PurposeAs an important reference index for the early diagnosis of non-small cell lung cancer (NSCLC), CYFRA21-1 still lacks the detection of low equipment cost, wide linear range and high sensitivity. Surface-enhanced Raman scattering (SERS) is a vibration spectrum technology based on the surface plasma of precious metal nanoparticles, which has been effectively applied to the detection of tumor markers. The combination of SERS technology and sensors has great potential in the ultrasensitive detection of tumor markers. The purpose of this study was to develop a sensitive method using SERS to quantitatively detect CYFRA21-1 for early diagnosis of NSCLC. MethodsA double-antibody sandwich immunoassay based on SERS was designed and tested to implement the ultrasensitive detection of CYFRA21-1 in the serum of NSCLC patients. ResultsGold @Ag nanorods (Au @Ag NRs) with higher Raman signals were prepared and used as probes, while magnetic graphene oxide was used as a magnetic substrate. The immunized probe, immune substrate and CYFRA21-1 standard substance in the buffer system formed a double-antibody sandwich structure. The standard curve displayed a liner range from 1pg mL−1 to 10 ng mL−1, and the detection limit (LOD) is 0.8943pg mL−1. The Raman intensity exhibited a wide linear relationship with the logarithm of CYFRA21-1 concentration. ConclusionOur study successfully established a double-antibody sandwich immunoassay based on SERS. This method demonstrated high specificity and sensitivity for detecting CYFRA21-1 protein content in serum. It has the potential to be applied for early detection of lung cancer biomarkers.

Electrochemical Sensor for the Detection and Accurate Early Diagnosis of Ovarian Cancer.

Ovarian cancer (OC) has the highest mortality rate among malignant tumors, primarily because it is difficult to diagnose early. Exosomes, a type of extracellular vesicle rich in parental information, have garnered significant attention in the field of cancer diagnosis and treatment. They play an important regulatory role in the occurrence, development, and metastasis of OC. Consequently, exosomes have emerged as noninvasive biomarkers for early cancer detection. Therefore, identifying cancer-derived exosomes may offer a novel biomarker for the early detection of OC. In this study, we developed a metal-organic frameworks assembled "double hook"-type aptamer electrochemical sensor, which enables accurate early diagnosis of OC. Under optimal experimental conditions, electrochemical impedance spectroscopy technology demonstrated a good linear relationship within the concentration range of 31-3.1 × 106 particles per microliter, with a detection limit as low as 12 particles per microliter. The universal exosome detection platform is constructed, and this platform can not only differentiate between high-grade serous ovarian cancer (HGSOC) patients and healthy individuals but also distinguish between HGSOC patients and nonhigh-grade serous OC (non-HGSOC). Consequently, it provides a novel strategy for the early diagnosis of OC and holds great significance in clinical differential diagnosis.

Abstract A005: Exploring liquid biopsy for the detection of bladder cancer: Unraveling RNA fusions

Abstract Introduction: This study delves into the promising realm of liquid biopsy for the non-invasive detection of bladder cancer. Leveraging urine as a valuable source, our investigation focuses on identifying RNA fusions associated with bladder cancer, with specific attention to ETV6-NTRK3 and PRCC-TFE3. The utilization of liquid biopsy offers a less invasive and more accessible approach to diagnosing bladder cancer, potentially revolutionizing the field of cancer diagnostics. These specific RNA fusions in urine samples may serve as reliable biomarkers for early detection and monitoring of bladder cancer. This research contributes to the ongoing efforts to enhance diagnostic methodologies to improve patient outcomes and streamline cancer management. Materials and Methods: Urine was collected from healthy male donors using UAS, a urine preservative from Novosanis, for improved urine preservation and stability. The urine samples with UAS were centrifuged at 16,000 xg for 10 min to obtain cf-urine. Three 20 mL aliquots of the precleared supernatant urine samples were spiked with an RNA fusion reference standard from Anchor Molecular containing ETV6-NTRK3 and PRCC-TFE3RNA at a concentration of 20ng/mL. All samples were extracted using the nRichDX Revolution Max20 cfTNA Isolation Kit. The eluants from the extracted samples were DNAse treated. The extracted cfTNAs profile was assessed on 4150 TapeStation System, Agilent, using RNA ScreenTape. Extracted nucleic acids from urine were evaluated using a RT-qPCR assay to quantify the number of copies of the fusion RNAs. Results: The Renal RNA fusions ETV6-NTRK3 and PRCC-TFE3RNA were successfully extracted using the nRichDX Revolution cfTNA Isolation Kit. TapeStation analysis demonstrated prominent 18S and 28S peaks, confirming the successful extraction of RNA from 20 mL urine samples. The mean percent recovery of the recovered RNA Fusion mutation was about 70% via RT-qPCR. Conclusion: Our findings indicate a recovery rate of approximately 70% for spiked RNA fusions in the urine samples. This research holds the promise of revolutionizing cancer diagnostics by introducing a method that is not only reliable but also convenient for early detection and monitoring. Identifying specific RNA fusions in urine samples as biomarkers is a significant step in enhancing diagnostic methodologies. As we contribute to these ongoing efforts, we aim to improve patient outcomes and streamline the management of bladder cancer through innovative and effective diagnostic approaches. Citation Format: Mayer Saidian, Jason Saenz, Carlos Hernandez, Lauren Lee, Andrew Dunnigan, Yabin Lu, Nafiseh Jafari. Exploring liquid biopsy for the detection of bladder cancer: Unraveling RNA fusions [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A005.

Molecular analysis for ovarian cancer detection in patient-friendly samples

BackgroundHigh ovarian cancer mortality rates motivate the development of effective and patient-friendly diagnostics. Here, we explored the potential of molecular testing in patient-friendly samples for ovarian cancer detection.MethodsHome-collected urine, cervicovaginal self-samples, and clinician-taken cervical scrapes were prospectively collected from 54 patients diagnosed with a highly suspicious ovarian mass (benign n = 25, malignant n = 29). All samples were tested for nine methylation markers, using quantitative methylation-specific PCRs that were verified on ovarian tissue samples, and compared to non-paired patient-friendly samples of 110 age-matched healthy controls. Copy number analysis was performed on a subset of urine samples of ovarian cancer patients by shallow whole-genome sequencing.ResultsThree methylation markers are significantly elevated in full void urine of ovarian cancer patients as compared to healthy controls (C2CD4D, P = 0.008; CDO1, P = 0.022; MAL, P = 0.008), of which two are also discriminatory in cervical scrapes (C2CD4D, P = 0.001; CDO1, P = 0.004). When comparing benign and malignant ovarian masses, GHSR shows significantly elevated methylation levels in the urine sediment of ovarian cancer patients (P = 0.024). Other methylation markers demonstrate comparably high methylation levels in benign and malignant ovarian masses. Cervicovaginal self-samples show no elevated methylation levels in patients with ovarian masses as compared to healthy controls. Copy number changes are identified in 4 out of 23 urine samples of ovarian cancer patients.ConclusionsOur study reveals increased methylation levels of ovarian cancer-associated genes and copy number aberrations in the urine of ovarian cancer patients. Our findings support continued research into urine biomarkers for ovarian cancer detection and highlight the importance of including benign ovarian masses in future studies to develop a clinically useful test.

Deep Neural Network-Assisted Terahertz Metasurface Sensors for the Detection of Lung Cancer Biomarkers

Deep Neural Network-Assisted Terahertz Metasurface Sensors for the Detection of Lung Cancer Biomarkers

Machine learning unveils an immune-related DNA methylation profile in germline DNA from breast cancer patients

BackgroundThere is an unmet need for precise biomarkers for early non-invasive breast cancer detection. Here, we aimed to identify blood-based DNA methylation biomarkers that are associated with breast cancer.MethodsDNA methylation profiling was performed for 524 Asian Chinese individuals, comprising 256 breast cancer patients and 268 age-matched healthy controls, using the Infinium MethylationEPIC array. Feature selection was applied to 649,688 CpG sites in the training set. Predictive models were built by training three machine learning models, with performance evaluated on an independent test set. Enrichment analysis to identify transcription factors binding to regions associated with the selected CpG sites and pathway analysis for genes located nearby were conducted.ResultsA methylation profile comprising 51 CpGs was identified that effectively distinguishes breast cancer patients from healthy controls achieving an AUC of 0.823 on an independent test set. Notably, it outperformed all four previously reported breast cancer-associated methylation profiles. Enrichment analysis revealed enrichment of genomic loci associated with the binding of immune modulating AP-1 transcription factors, while pathway analysis of nearby genes showed an overrepresentation of immune-related pathways.ConclusionThis study has identified a breast cancer-associated methylation profile that is immune-related to potential for early cancer detection.

Electrochemical Detection of a Breast Cancer Biomarker with an Amine-Functionalized Nanocomposite Pt-Fe3O4-MWCNTs-NH2 as a Signal-Amplifying Label.

We report an ultrasensitive sandwich-type electrochemical immunosensor to detect the breast cancer biomarker CA 15-3. Amine-functionalized composite of reduced graphene oxide and Fe3O4 nanoparticles (MRGO-NH2) was used as an electrochemical sensing platform material to modify the electrodes. The nanocomposite comprising Pt and Fe3O4 nanoparticles (NPs) anchored on multiwalled carbon nanotubes (Pt-Fe3O4-MWCNTs-NH2) was utilized as a pseudoenzymatic signal-amplifying label. Compared to reduced graphene oxide, the composite MRGO-NH2 platform material demonstrated a higher electrochemical signal. In the Pt-Fe3O4-MWCNTs-NH2 label, multiwalled carbon nanotubes provided the substratum to anchor abundant catalytic Pt and Fe3O4 NPs. The nanocomposites were thoroughly characterized using transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and X-ray photoelectron spectroscopy. An electroanalytical study and prevalidation of the immunosensor was carried out. The immunosensor exhibited exceptional capabilities in detecting CA 15-3, offering a wider linear range of 0.0005-100 U mL-1 and a lower detection limit of 0.00008 U mL-1. Moreover, the designed immunosensor showed good specificity, reproducibility, and acceptable stability. The sensor was successfully applied to analyze samples from breast cancer patients, yielding reliable results.

Cycling back to folate metabolism in cancer.

Metabolic changes contribute to cancer initiation and progression through effects on cancer cells, the tumor microenvironment and whole-body metabolism. Alterations in serine metabolism and the control of one-carbon cycles have emerged as critical for the development of many tumor types. In this Review, we focus on the mitochondrial folate cycle. We discuss recent evidence that, in addition to supporting nucleotide synthesis, mitochondrial folate metabolism also contributes to metastasis through support of antioxidant defense, mitochondrial protein synthesis and the overflow of excess formate. These observations offer potential therapeutic opportunities, including the modulation of formate metabolism through dietary interventions and the use of circulating folate cycle metabolites as biomarkers for cancer detection.

Abstract PO5-07-08: A Serum Biomarker for the Early Detection of Breast cancer

Abstract Background: After decades of use, clinicians and medical societies are still debating on the clinical utility of mammography, the standard of care for breast cancer (BC) screening, because of its limitations such as subjective visual interpretation, high rate of false-positive and false-negative (in dense breast) and concerns over radiation exposure. There are 55 million women, and about 45% of them considered dense breast, in need of an accurate, easy to use test for the screening of BC regardless of breast tissue complexities to differentiate between BC and benign findings such as calcification and fibrosis. To this date there is no blood protein biomarker (BM) in clinical use for the early detection of BC. We have developed a novel BC specific protein biomarker -based blood test to detect patients with early-stage BC and established herein the diagnostic performance of our BM in discriminating BC patients from healthy individuals and benign breast cases. Methods: A total of 433 serum samples (318 primary BC, 32 benign breast and 83 normal breast) were obtained from the Cooperative Human Tissue Network and from the IRCCS San Raffaele Pisana Research Center (blind samples). 247 BC samples were provided as blind samples and were used to validate the screening utility. Serum samples were tested with our BC specific BM by sandwich ELISA. Receiver operating characteristic (ROC) curves were calculated to evaluate the diagnostic performance, by determining sensitivity (SE), specificity (SP), area under the curve (AUC), and confidence interval (CI). Statistical analysis, ROC curves and scatter plots were performed with GraphPad Prism 7.0. Results: BM elevation in early cancer cases (stage I-II, Ductal Carcinoma) was found to be statistically significant (p< 0.0001) as compared to healthy and benign cases. Our test discriminated early BC patients from non-cancer cases with 87.3% SE at 85.2% SP and was further validated in a blind set including 247 BC (Ductal & Lobular Carcinoma, stage I-III), 30 benign and 83 normal breast cases (88%SE, 86%SP). The sensitivity for early-stage (I-II) and late stage (III) BC was 86.8% and 94.3%, respectively. While lobular carcinoma is particularly not well detected by mammography with a sensitivity as low as 57% and much lower for women with dense breast, it was detected with high sensitivity (90%) in our test. 80% of fibrocystic changes (FCC), the most common form of benign breast disease in women over 50 years of age were negative with our test. Although it is a benign condition, FCC may be misdiagnosed as a malignant lesion by physical examination and imaging. Conclusion: Our results support the utility of our blood-based test for the early detection of breast cancer which presents improved features over mammography such as higher lobular cancer sensitivity, lower detection rate of common form of benign condition often misdiagnosed by imaging, absence of radiation and expected high compliance. Further testing is needed to confirm accuracy of our test in the dense breast population. Citation Format: Christine Chavany, Jeffrey Dea, Monica Guevara, Rafael Hernandez-Gonzalez, Patrizia Ferroni, Fiorella Guadagni, Rosaura Valle, Moncef Jendoubi. A Serum Biomarker for the Early Detection of Breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-07-08.

Investigating alterations in amino acid levels and immune cell population as potential biomarkers for non-invasive early detection of breast cancer: Insights from a study in north India

Investigating alterations in amino acid levels and immune cell population as potential biomarkers for non-invasive early detection of breast cancer: Insights from a study in north India

Circulating MiR-1185¸ MiR-3183, and MiR-584 Levels in Plasma as Diagnostic Non-invasive Biomarkers for Early Detection of Breast Cancer

Introduction: MicroRNAs (miRNAs) are non-coding RNA molecules with short sequences that function as main post-transcriptional gene regulators of different biological pathways via negative regulation of gene expression, thereby leading to either mRNA degradation or translational blockade. Dysregulated expression of these miRNAs has been related etiologically to many human diseases, including breast cancer. Various cellular processes of breast cancer progression, including cell proliferation, apoptosis, metastasis, recurrence and chemodrug resistance, are modulated by oncogenic miRNA (oncomiR). Objective: The objective of this investigation was to study the expression level and potential diagnostic/ prognostic roles of circulating microRNAs (miR-3183, miR-1185, and miR-584) as novel breast cancer biomarkers. Method: The current study was conducted on 99 breast cancer (BC) female patients, aged between 20-63 years old, as the case group and 50 age-matched healthy females as control (HC). After microRNA extraction from the serum samples, real-time PCR was carried out for relative expression quantification of miR-1185, miR-3183a, and miR-584. The ROC curve analysis was performed to investigate the diagnostic value of miRNAs. Result: It was demonstrated that miRNA-1185, miRNA-584, and miRNA-3183 were significantly up-regulated (p-values <0.0001) in female BC cases compared to the control group. Besides, based on the ROC analysis for BC versus HC, it was revealed that the AUC for miRNA-584 was 0.844 (95% confidence interval (CI) and could be proposed as a diagnostic biomarker for breast cancer screening and follow-up. Conclusion: MiRNAs expression profiling using blood-based samples demonstrated their upregulation in the serum and plasma and revealed the concept that circulating miRNAs have high potential as novel noninvasive biomarkers for cancer diagnosis and screening.

Role of MicroRNA in Hypoxic Tumours and their Potential as Biomarkers for Early Detection of Cancer.

Hypoxia is a pathophysiological condition characterized by oxygen deficiency in tissues, which negatively affects normal biological functions. It is a typical microenvironment character of almost all solid tumours. Noncoding RNA are small functional RNA molecules that regulate gene expression at chromatin and posttranscriptional levels. Micro-RNAs (miRNAs) are a type of noncoding RNA and are ~12-22 nucleotides long that are crucial in regulating gene expression by partnering with the mRNAs of protein-coding genes. It is widely reported that miRs play an important role in various key processes and pathways during tumour formation, as well as advancement in hypoxic tumors by influencing the HIF pathway. The role of miRNAs in hypoxic tumours, namely in pancreatic, kidney, breast, lung and colorectal, are described. These miRNAs have immense potential as diagnostic and prognostic biomarkers for early cancer detection.

Recent Trends and Innovations in Bead-Based Biosensors for Cancer Detection.

Demand is strong for sensitive, reliable, and cost-effective diagnostic tools for cancer detection. Accordingly, bead-based biosensors have emerged in recent years as promising diagnostic platforms based on wide-ranging cancer biomarkers owing to the versatility, high sensitivity, and flexibility to perform the multiplexing of beads. This comprehensive review highlights recent trends and innovations in the development of bead-based biosensors for cancer-biomarker detection. We introduce various types of bead-based biosensors such as optical, electrochemical, and magnetic biosensors, along with their respective advantages and limitations. Moreover, the review summarizes the latest advancements, including fabrication techniques, signal-amplification strategies, and integration with microfluidics and nanotechnology. Additionally, the challenges and future perspectives in the field of bead-based biosensors for cancer-biomarker detection are discussed. Understanding these innovations in bead-based biosensors can greatly contribute to improvements in cancer diagnostics, thereby facilitating early detection and personalized treatments.