Integrated DNA methylation analysis of peripheral blood from asbestos exposed populations and patients with malignant mesothelioma reveals novel methylation driver genes of diagnostic and prognostic relevance.

Effective biomarkers are paramount importance for the early detection and prognosis prediction of malignant mesothelioma (MM) which mainly caused by asbestos exposure, and DNA methylation has been demonstrated to be a potentially powerful diagnostic tool. To elucidate the relationship between asbestos exposure and alterations in DNA methylation patterns, as well as the potential diagnostic and prognostic value of differentially methylated regions and CpG sites (DMRs/DMCs) in the progression of MM. The current study employed reduced representation bisulfite sequencing (RRBS) to examine the genome-wide DNA methylation profiles in the peripheral blood of individuals exposed to asbestos and those diagnosed with MM, in comparison to the controls, and DMRs/DMCs were subsequently validated by targeted bisulfite sequencing (TBS). Our results suggested that there were 12 DMRs/DMCs exhibiting a consistent change trend of DNA methylation in both RRBS and TBS results. Significant correlations were observed between DNA methylation levels of DMRs/DMCs and the duration of occupational asbestos exposure. The evaluation of the receiver operating characteristic (ROC) curve suggested that the DNA methylation status of FHIT, CCR12P and CDH15 may serve as diagnosis indicator in distinguishing MM patients from healthy controls and those exposed to asbestos. Our findings offer a foundation for the role of DNA methylation in the development of MM induced by asbestos exposure. The potential significance of FHIT, CCR12P and CDH15 DNA methylation alterations in the pathogenesis and advancement of MM disease suggests their potential as diagnostic and prognostic biomarkers.

Liquid biopsy for diagnostic and prognostic evaluation of melanoma.

Melanoma is the most aggressive form of skin cancer, and the majority of cases are associated with chronic or intermittent sun exposure. The incidence of melanoma has grown exponentially over the last 50 years, especially in populations of fairer skin, at lower altitudes and in geriatric populations. The gold standard for diagnosis of melanoma is performing an excisional biopsy with full resection or an incisional tissue biopsy. However, due to their invasiveness, conventional biopsy techniques are not suitable for continuous disease monitoring. Utilization of liquid biopsy techniques represent substantial promise in early detection of melanoma. Through this procedure, tumor-specific components shed into circulation can be analyzed for not only diagnosis but also treatment selection and risk assessment. Additionally, liquid biopsy is significantly less invasive than tissue biopsy and offers a novel way to monitor the treatment response and disease relapse, predicting metastasis.

From sequencing to validation: NGS-based exploration of plasma miRNA in papillary thyroid carcinoma.

Objective: A non-invasive method using plasma microRNAs provides new insights into thyroid cancer diagnosis. The objective of this study was to discover potential circulating biomarkers of papillary thyroid carcinoma (PTC) through the analysis of plasma miRNAs using next-generation sequencing (NGS). Methods: Plasma miRNAs were isolated from peripheral blood samples collected from healthy individuals, patients diagnosed with PTC, and those with benign thyroid nodules. The Illumina NovaSeq 6000 platform was employed to establish the miRNA expression profiles. Candidate miRNAs for diagnostic purposes were identified utilizing the Random Forest (RF) algorithm. The selected miRNAs were subsequently validated in an independent validation set using RT-qPCR. Results: NGS results revealed consistent plasma miRNA expression patterns among healthy individuals and patients with benign thyroid nodules in the discovery set (6 healthy cases, 17 benign cases), while differing significantly from those observed in the PTC group (17 PTC cases). Seven miRNAs exhibiting significant expression differences were identified and utilized to construct an RF classifier. Receiver operating characteristic (ROC) analysis for PTC diagnosis, and the area under the curve (AUC) was 0.978. Subsequent KEGG and GO analyses of the target genes associated with these 7 miRNAs highlighted pathways relevant to tumors and the cell cycle. Independent validation through RT-qPCR in a separate cohort (15 CONTROL, 15 PTC groups) underscored hsa-miR-301a-3p and hsa-miR-195-5p as promising candidates for PTC diagnosis. Conclusion: In conclusion, our study established a seven-miRNA panel in plasma by Random Forest algorithm with significant performance in discriminating PTC from healthy or benign group. hsa-miR-301a-3p, hsa-miR-195-5p in plasma have potential for further study in the diagnosis of PTC in Asian ethnic.

Exploring non-invasive diagnostics for metabolic dysfunction-associated fatty liver disease.

The population with metabolic dysfunction-associated fatty liver disease (MAFLD) is increasingly common worldwide. Identification of people at risk of progression to advanced stages is necessary to timely offer interventions and appropriate care. Liver biopsy is currently considered the gold standard for the diagnosis and staging of MAFLD, but it has associated risks and limitations. This has spurred the exploration of non-invasive diagnostics for MAFLD, especially for steatohepatitis and fibrosis. These non-invasive approaches mostly include biomarkers and algorithms derived from anthropometric measurements, serum tests, imaging or stool metagenome profiling. However, they still need rigorous and widespread clinical validation for the diagnostic performance.

Circulating microRNAs as biomarkers for stratifying different phases of liver cancer progression and response to therapy.

Hepatocellular carcinoma (HCC) is the most common liver cancer and is among the leading causes of cancer-related death worldwide. There is no reliable biomarker for the early diagnosis of HCC. Circulating microRNAs (miRNAs) have attracted attention as potential biomarkers of disease. By small-RNA next-generation sequencing, the analysis of serum miRNAs led to the identification of molecular signatures able to discriminate advanced HCC from early HCC (n = 246); advanced HCC from CIRRHOSIS (n = 299); advanced HCC from HEALTHY (n = 320); HEALTHY from early HCC (n = 343); and HEALTHY from CIRRHOSIS (n = 414). Cirrhotic patients and early HCC patients exhibited similar serum miRNA profiles, yet a small number of miRNAs (n = 57) were able to distinguish these two classes of patients. A second objective of the study was to identify serum miRNAs capable of predicting the response to therapy in patients with advanced HCC. All patients were treated with sorafenib as first-line therapy: 24 were nonresponsive and 24 responsive. Analysis of circulating miRNAs revealed a 54 miRNAs signature able to separate the two subgroups. This study suggested that circulating miRNAs could be useful biomarkers for monitoring patients with liver diseases ranging from cirrhosis to advanced HCC and possibly predicting susceptibility to first-line treatment based on sorafenib.

The cross-talk between the macro and micro-environment in precursor lesions of pancreatic cancer leads to new and promising circulating biomarkers.

Pancreatic cancer (PC) is a clinically challenging tumor to combat due to its advanced stage at diagnosis as well as its resistance to currently available therapies. The absence of early symptoms and known detectable biomarkers renders this disease incredibly difficult to detect/manage. Recent advances in the understanding of PC biology have highlighted the importance of cancer-immune cell interactions, not only in the tumor micro-environment but also in distant systemic sites, like the bone marrow, spleen and circulating immune cells, the so-called macro-environment. The response of the macro-environment is emerging as a determining factor in tumor development by contributing to the formation of an increasingly immunogenic micro-environment promoting tumor homeostasis and progression. We will summarize the key events associated with the feedback loop between the tumor immune micro-environment (TIME) and the tumor immune macroenvironment (TIMaE) in pancreatic precancerous lesions along with how it regulates disease development and progression. In addition, liquid biopsy biomarkers capable of diagnosing PC at an early stage of onset will also be discussed. A clearer understanding of the early crosstalk between micro-environment and macro-environment could contribute to identifying new molecular therapeutic targets and biomarkers, consequently improving early PC diagnosis and treatment.

An overview of circulating and urinary biomarkers capable of predicting the transition of acute kidney injury to chronic kidney disease.

INTRODUCTION: Acute kidney injury (AKI) defined by a substantial decrease in kidney function within hours to days and is often irreversible with higher risk to chronic kidney disease (CKD) transition. AREAS COVERED: The authors discuss the diagnostic and predictive utilities of serum and urinary biomarkers on AKI and on the risk of AKI-to-CKD progression. The authors focus on the relevant literature covering evidence of circulating and urinary biomarkers' capability to predict the transition of AKI to CKD. EXPERT OPINION: Based on the different modalities of serum and urinary biomarkers, multiple biomarker panel seems to be potentially useful to distinguish between various types of AKI, to detect the severity and the risk of AKI progression, to predict the clinical outcome and evaluate response to the therapy. Serum/urinary neutrophil gelatinase-associated lipocalin (NGAL), serum/urinary uromodulin, serum extracellular high mobility group box-1 (HMGB-1), serum cystatin C and urinary liver-type fatty acid-binding protein (L-FABP) were the most effective in the prediction of AKI-to-CKD transition regardless of etiology and the presence of critical state in patients. The current clinical evidence on the risk assessments of AKI progression is mainly based on the utility of combination of functional, injury and stress biomarkers, mainly NGAL, L-FABP, HMGB-1 and cystatin C.

Circulating Biomarkers Predictive of Treatment Response in Patients with Hormone-sensitive or Castration-resistant Metastatic Prostate Cancer: A Systematic Review.

BACKGROUND AND OBJECTIVE: Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also directly in biologic fluids (ie, liquid biopsies), mainly blood. Liquid biopsies may represent a safer and less invasive alternative for monitoring patients treated for mPCa. Current research focuses on the description and validation of novel predictive biomarkers to improve precision medicine in mPCa. Our aim was to systematically review the current evidence on liquid biopsy biomarkers for predicting treatment response in mPCa. METHODS: We systematically searched Medline, Web of Science, and evidence-based websites for publications on circulating biomarkers in mPCa between March 2013 and February 2024 for review. Endpoints were: prediction of overall survival, biochemical or radiographic progression-free survival after treatment (chemotherapy, androgen deprivation therapy, androgen receptor pathway inhibitors [ARPIs], immunotherapy, or PARP inhibitors [PARPIs]). For each biomarker, the level of evidence (LOE) for clinical validity was attributed: LOE IA and IB, high level of evidence; LOE IIB and IIC, intermediate level; and LOE IIIC and LOE IV-VD, weak level. KEY FINDINGS AND LIMITATIONS: The predictive value of each biomarker for the response to several therapies was evaluated in both metastatic hormone-sensitive (mHSPC) and castration-resistant prostate cancer (mCRPC). In patients with mCRPC, BRCA1/2 or ATM mutations predicted response to ARPIs (LOE IB) and PARPIs (LOE IIB), while AR-V7 transcripts or AR-V7 protein levels in circulating tumor cells (CTCs) predicted response to ARPIs and taxanes (LOE IB). CTC quantification predicted response to cabazitaxel, abiraterone, and radium-223 (LOE IIB), while TP53 alterations predicted response to 177Lu prostate-specific membrane antigen radioligand treatment (LOE IIB). AR copy number in circulating tumor DNA before the first treatment line and before subsequent lines predicted response to docetaxel, cabazitaxel, and ARPIs (LOE IIB). In mHSPC, DNA damage in lymphocytes was predictive of the response to radium-223 (LOE IIB). CONCLUSIONS AND CLINICAL IMPLICATIONS: BRCA1/2, ATM, and AR alterations detected in liquid biopsies may help clinicians in management of patients with mPCa. The other circulating biomarkers did not reach the LOE required for routine clinical use and should be validated in prospective independent studies. PATIENT SUMMARY: We reviewed studies assessing the value of biomarkers in blood or urine for management of metastatic prostate cancer. The evidence indicates that some biomarkers could help in selecting patients eligible for specific treatments.

Circulating biomarkers as predictors of response to immune checkpoint inhibitors in NSCLC: Are we on the right path?

Immune checkpoints inhibitors (ICIs) have markedly improved the therapeutic management of advanced NSCLC and, more recently, they have demonstrated efficacy also in the early-stage disease. Despite better survival outcomes with ICIs compared to standard chemotherapy, a large proportion of patients can derive limited clinical benefit from these agents. So far, few predictive biomarkers, including the programmed death-ligand 1 (PD-L1), have been introduced in clinical practice. Therefore, there is an urgent need to identify novel biomarkers to select patients for immunotherapy, to improve efficacy and avoid unnecessary toxicity. A deeper understanding of the mechanisms involved in antitumor immunity and advances in the field of liquid biopsy have led to the identification of a wide range of circulating biomarkers that could potentially predict response to immunotherapy. Herein, we provide an updated overview of these circulating biomarkers, focusing on emerging data from clinical studies and describing modern technologies used for their detection.

Immunotherapy in melanoma: Can we predict response to treatment with circulating biomarkers?

Melanoma is the most aggressive form of skin cancer, representing approximately 4% of all cutaneous neoplasms and accounting for up to 80% of deaths. Advanced stages of melanoma involve metastatic processes and are associated with high mortality and morbidity, mainly due to the rapid dissemination and heterogeneous responses to current therapies, including immunotherapy. Immune checkpoint inhibitors (ICIs) are currently used in the treatment of metastatic melanoma (MM) and despite being linked to an increase in patient survival, a high percentage of them still do not benefit from it. Accordingly, the number of therapeutic regimens for MM patients using ICIs either alone or in combination with other therapies has increased, together with the need for reliable biomarkers that can both predict and monitor response to ICIs. In this context, circulating biomarkers, such as DNA, RNA, proteins, and cells, have emerged due to their ability to reflect disease status. Moreover, blood tests are minimally invasive and provide an attractive option to detect biomarkers, avoiding stressful medical procedures. This systematic review aims to evaluate the possibility of a non-invasive biomarker signature that can guide therapeutic decisions. The studies reported here offer valuable insight into how circulating biomarkers can have a role in personalized treatments for melanoma patients receiving ICIs therapy, emphasizing the need for rigorous clinical trials to confirm findings and establish standardized procedures.

MicroRNAs as Plasma Biomarkers of Hepatocellular Carcinoma in Patients with Liver Cirrhosis-A Cross-Sectional Study.

Ultrasound screening for hepatocellular carcinoma (HCC) in patients with liver cirrhosis has a poor sensitivity for small tumors. Circulating microRNAs (miRNAs) have been explored as HCC biomarkers, but results are diverging. Here, we evaluate if miRNAs up-regulated in HCC tissue can be detected in plasma and used as screening biomarkers for HCC. In this cross-sectional study, plasma, HCC tissue and surrounding non-tumorous liver tissue were collected from liver resections. Tissue miRNAs were identified and quantitated by RNA-sequencing analysis, and the fold-changes between HCC and surrounding liver tissue were calculated. The miRNAs up-regulated in HCCs were then re-analyzed in plasma from the same patients, and the miRNAs with the highest plasma levels were subsequently measured in plasma from an independent cohort of patients with cirrhosis or HCC. In tissues from 84 resected patients, RNA-sequencing detected 197 differentially expressed miRNAs, 40 of which had a raw count above 200 and were analyzed in plasma from the same cohort. Thirty-one miRNAs were selected for further analysis in 200 patients with HCC or cirrhosis. Of these, eleven miRNAs were significantly increased in HCC as compared to cirrhosis patients. Only miR-93-5p and miR-151a-3p were significantly associated with HCC, with an AUC of 0.662. In comparison, alpha-fetoprotein and des-gamma-carboxy prothrombin yielded an AUC of 0.816, which increased to 0.832 if miR-93-5p and miR-151a-3p were added. When including sex and age, the addition of miR-93-5p and miR-151a-3p did not further improve the AUC (from 0.910 to 0.911). In conclusion, micro-RNAs up-regulated in HCCs are detectable in plasma but have a poor performance as screening biomarkers of HCC.

Older adults, appendicular anthropometric measurements, and poor functional performance are predictors of sarcopenia in individuals with head and neck squamous cell carcinoma.

OBJECTIVE: To identify predictors of sarcopenia (demographical, anthropometric measurements, tumor-related clinical characteristics, performance status, and serum C-reactive protein (CRP) and albumin levels in individuals with head and neck squamous cell carcinoma (HNSCC). MATERIAL AND METHODS: This cross-sectional study selected diagnosed with HNSCC (n = 125). Sarcopenia was defined as low muscle strength and low physical performance. Association between sarcopenia and anthropometric assessments (weight, height, body mass index, triceps skinfold, mid-upper arm circumference [MUAC], mid-upper arm muscle circumference, mid-upper arm fat area [UFA], mid-upper arm bone free muscle area, calf circumference, and appendicular skeletal muscle mass and index), tumor clinical characteristics (anatomical site, tumor size, and cervical metastasis), performance status scale (Eastern Cooperative Oncology Group Performance Status [ECOG-PS]), and CRP and albumin levels was analyzed using binary logistic regression models. RESULTS: The diagnosis of sarcopenia was identified in 28 (22.4%) individuals with HNSCC. Being an older adult increases the odds of association with sarcopenia in individuals with HNSCC (odds ratio [OR] = 1.05). Increments in MUAC measurement reduce the odds of association with sarcopenia (OR = 0.69), while the increase in the UFA measurement increases the odds of association with sarcopenia (OR = 1.33). Poor ECOG-PS scores increase the odds of association with sarcopenia in individuals with HNSCC (OR = 5.54). CONCLUSION: Early identification of easy-to-perform, cost-effective predictors of sarcopenia tends to favor the implementation of personalized therapeutic and supportive interventions in individuals with HNSCC.

Tumor circulating biomarkers in colorectal cancer.

CRC is a major global health concern and is responsible for a significant number of cancer-related deaths each year. The successful treatment of CRC becomes more difficult when it goes undetected until it has advanced to a later stage. Diagnostic biomarkers can play a critical role in the early detection of CRC, which leads to improved patient outcomes and increased survival rates. It is important to develop reliable biomarkers for the early detection of CRC to enable timely diagnosis and treatment. To date, CRC detection methods such as endoscopy, blood, and stool tests are imperfect and often only identify cases in the later stages of the disease. To overcome these limitations, researchers are turning to molecular biomarkers as a promising avenue for improving CRC detection. Diagnostic information can be provided more reliably through a noninvasive approach using biomarkers such as mRNA, circulating cell-free DNA, micro-RNA, long non-coding RNA, and proteins. These biomarkers can be found in blood, tissue, feces, and volatile organic compounds. The identification of molecular biomarkers with high sensitivity and specificity for early detection of CRC that are safe, cost-effective, and easily measurable remains a significant challenge for researchers. In this article, we will explore the latest advancements in blood-based diagnostic biomarkers for CRC and their potential impact on improving patient survival rates.

Circulating biomarkers of the CS4P and CLIP scores are not altered in a pig model of acute cardiogenic shock and additional short-term circulatory support.

BACKGROUND: Cardiogenic shock (CS) is the leading cause of death in patients with myocardial infarction with a mortality rate greater than 50%. Recently, the CS 4 Proteins (CS4P) and CLIP scores have been developed to predict survival in CS patients. However, their impact in acute CS and additional short-term left ventricular (LV) circulatory support as prognostic markers is currently not known. METHODS AND RESULTS: CS was induced in a porcine model by injecting microsphere particles into the left main coronary artery. Mechanical circulatory support was performed by additional percutaneous LV unloading using an Impella microaxial flow-pump for 30 minutes. Serum samples were collected at baseline, following the onset of CS, and additional LV unloading. Serum levels of biomarkers of the CS4P (beta-2-microglobulin, ALDOB, L-FABP, SerpinG1) and the CLIP scores (Cystatin C, Lactate, Interleukin-6, NT-proBNP) were neither different at any time point investigated nor did they correlate with cardiac output. CONCLUSION: The CS4P and CLIP scores do not reflect immediate whole-body dysregulation in acute CS and have not been able to predict the potential reversal following additional short-term mechanical support by LV unloading in our experimental model. The impact of both scores as prognostic markers after the immediate onset of CS and following additional short-term LV unloading to identify patients at greatest risk remains to be determined.

Predictors of Kidney Function Outcomes and Their Relation to SGLT2 Inhibitor Dapagliflozin in Patients with Type 2 Diabetes Mellitus Who Had Chronic Heart Failure.

INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have a favorable impact on the kidney function in patients with heart failure (HF), while there is no clear evidence of what factors predict this effect. The aim of the study was to identify plausible predictors for kidney function outcome among patients with HF and investigate their association with SGLT2i. METHODS: We prospectively enrolled 480 patients with type 2 diabetes mellitus (T2DM) treated with diet and metformin and concomitant chronic HF and followed them for 52 weeks. In the study, we determined kidney outcome as a composite of ≥ 40% reduced estimated glomerular filtration rate from baseline, newly diagnosed end-stage kidney disease or kidney replacement therapy. The relevant medical information and measurement of the biomarkers (N-terminal natriuretic pro-peptide, irisin, apelin, adropin, C-reactive protein, tumor necrosis factor-alpha) were collected at baseline and at the end of the study. RESULTS: The composite kidney outcome was detected in 88 (18.3%) patients of the entire population. All patients received guideline-recommended optimal therapy, which was adjusted to phenotype/severity of HF, cardiovascular risk and comorbidity profiles, and fasting glycemia. Levels of irisin, adropin and apelin significantly increased in patients without clinical endpoint, whereas in those with composite endpoint the biomarker levels exhibited a decrease with borderline statistical significance (p = 0.05). We noticed that irisin ≤ 4.50 ng/ml at baseline and a ≤ 15% increase in irisin serum levels added more valuable predictive information than the reference variable. However, the combination of irisin ≤ 4.50 ng/ml at baseline and ≤ 15% increase in irisin serum levels (area under curve = 0.91; 95% confidence interval = 0.87-0.95) improved the discriminative value of each biomarker alone. CONCLUSION: We suggest that low levels of irisin and its inadequate increase during administration of SGLT2i are promising predictors for unfavorable kidney outcome among patients with T2DM and concomitant HF.

Precision Isolation of Circulating Leukemia Cells in Chronic Myelogenous Leukemia Patients Using a Novel Microfluidic Device and Its Clinical Applications.

Chronic Myelogenous Leukemia (CML) is a prevalent hematologic malignancy characterized by the malignant transformation of myeloid cells and their proliferation in the peripheral blood. The management of CML poses significant challenges, particularly in detecting and eradicating minimal residual disease, which is crucial for preventing relapse and improving survival outcomes. Traditional minimal residual disease detection methods, such as bone marrow aspiration, are invasive and have limitations which include the potential for sampling errors and false negatives. This study introduces a novel label-free microfluidic chip designed for the segregation and recovery of circulating leukemia cells, offering a non-invasive liquid biopsy approach with potential applications in precision medicine. Over July 2021 to October 2023, we recruited 56 CML patients across various disease stages and collected blood samples for analysis using our microfluidic device. The device demonstrated high efficacy in isolating circulating leukemia cells, with an optimal capture efficiency of 78% at a sample flow rate of 3 mL/h. Our results indicate that the microfluidic device can efficiently segregate and quantify circulating leukemia cells, providing a detailed understanding of CML progression and treatment response. The significant reduction in circulating leukemia cell counts in patients in complete remission highlights the device's potential in monitoring treatment efficacy. Furthermore, the device's sensitivity in detecting minimal residual disease could offer a more reliable prognostic tool for therapeutic decision-making in CML management.

Circulating Proteins as Diagnostic Markers in Gastric Cancer.

Gastric cancer (GC) is a highly malignant disease affecting humans worldwide and has a poor prognosis. Most GC cases are detected at advanced stages due to the cancer lacking early detectable symptoms. Therefore, there is great interest in improving early diagnosis by implementing targeted prevention strategies. Markers are necessary for early detection and to guide clinicians to the best personalized treatment. The current semi-invasive endoscopic methods to detect GC are invasive, costly, and time-consuming. Recent advances in proteomics technologies have enabled the screening of many samples and the detection of novel biomarkers and disease-related signature signaling networks. These biomarkers include circulating proteins from different fluids (e.g., plasma, serum, urine, and saliva) and extracellular vesicles. We review relevant published studies on circulating protein biomarkers in GC and detail their application as potential biomarkers for GC diagnosis. Identifying highly sensitive and highly specific diagnostic markers for GC may improve patient survival rates and contribute to advancing precision/personalized medicine.

Label-free microfluidic chip for segregation and recovery of circulating leukemia cells: clinical applications in acute myeloid leukemia.

We present a label-free microfluidic chip for the segregation of circulating leukemia cells (CLCs) from blood samples, with a focus on its clinical applications in Acute Myeloid Leukemia (AML). The microfluidic chip achieved an approximate capture efficiency of 92%. The study analyzed a comprehensive set of 66 blood specimens from AML patients in different disease stages, including newly diagnosed and relapsing cases, patients in complete remission, and those in partial remission. The results showed a significant difference in CLC counts between active disease stages and remission stages (p < 0.0001), with a proposed threshold of 5 CLCs to differentiate between the two. The microfluidic chip exhibited a sensitivity of 95.4% and specificity of 100% in predicting disease recurrence. Additionally, the captured CLCs were subjected to downstream molecular analysis using droplet digital PCR, allowing for the identification of genetic mutations associated with AML. Comparative analysis with bone marrow aspirate processing by FACS demonstrated the reliability and accuracy of the microfluidic chip in tracking disease burden, with highly agreement results obtained between the two methods. The non-invasive nature of the microfluidic chip and its ability to provide real-time insights into disease progression make it a promising tool for the proactive monitoring and personalized patient care of AML.

An Overview of Circulating Biomarkers in Neuroendocrine Neoplasms: A Clinical Guide.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of diseases that are characterized by different behavior and clinical manifestations. The diagnosis and management of this group of tumors are challenging due to tumor complexity and lack of precise and widely validated biomarkers. Indeed, the current circulating mono-analyte biomarkers (such as chromogranin A) are ineffective in describing such complex tumors due to their poor sensitivity and specificity. In contrast, multi-analytical circulating biomarkers (including NETest) are emerging as more effective tools to determine the real-time profile of the disease, both in terms of accurate diagnosis and effective treatment. In this review, we will analyze the capabilities and limitations of different circulating biomarkers focusing on three relevant questions: (1) accurate and early diagnosis; (2) monitoring of disease progression and response to therapy; and (3) detection of early relapse.

Immunotherapy-related biomarkers: Confirmations and uncertainties.

Immunotherapy profoundly changed oncology treatment, becoming one of the main therapeutical strategies. Remarkable improvement has been achieved in survival outcomes, but the percentage of patients who benefit from immunotherapy is still limited. Only one-third of patients receiving immune checkpoint inhibitors (ICIs) achieve long-term response. Several patients are not responsive to treatment or relapse after an initial response. To date, programmed death-ligand 1, microsatellite instability, and tumor mutational burden are the three biomarkers validated to predict the ICIs response, but a single variable seems still insufficient in the patient's selection. Considering the substantial and increasing use of these drugs, the identification of new predictive biomarkers of ICI response is of paramount importance. We summarize the state of the art and the clinical use of immune biomarkers in oncology, highlighting the strength and weaknesses of currently approved biomarkers, describing the emerging tissues and circulating biomarkers, and outlining future perspectives.