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Introduction: Almost one-quarter of immune checkpoint inhibitor (ICI) recipients experience sicca syndrome, while Sjögren's disease (SjD) is estimated at 0.3-2.5%, possibly underreported., Areas Covered: This narrative review (Medline/Embase until January/31/2024) addresses the pathophysiology, incidence, demographic/clinical features, biomarkers, labial salivary gland biopsy (LSGB), fulfillment of the idiopathic SjD (iSjD) classificatory criteria, differential diagnosis, and management of sicca syndrome/SjD associated with ICIs., Expert Opinion: SjD associated with ICIs is underdiagnosed, since studies that performed the mandatory SjD investigation identified that 40-60% of patients with sicca syndrome associated with ICIs meet the iSjD classificatory criteria. LSGB played a fundamental role in recognizing these cases, as most of them had negative anti-Ro/SS-A antibody. Despite the finding of focal lymphocytic sialoadenitis in LSGB samples mimicking iSjD, immunohistochemical analysis provided novel evidence of a distinct pattern for sicca syndrome/SjD associated with ICIs compared to iSjD. The former has scarcity of B lymphocytes, which are a hallmark of iSjD. Additionally, patients with sicca syndrome/SjD associated with ICIs have demographical/clinical/serological and treatment response dissimilarities compared to iSjD. Dryness symptoms are more acute in the former than in iSjD, with predominance of xerostomia over xerophthalmia, and partial/complete response to glucocorticoids. Dryness symptoms in ICI-treated patients warrant prompt SjD investigation.

The current constraints associated with cancer diagnosis and molecular profiling, which rely on invasive tissue biopsies or clinical imaging, have spurred the emergence of the liquid biopsy field. Liquid biopsy involves the extraction of circulating tumor cells (CTCs), circulating free or circulating tumor DNA (cfDNA or ctDNA), circulating cell-free RNA (cfRNA), extracellular vesicles (EVs), and tumor-educated platelets (TEPs) from bodily fluid samples. Subsequently, these components undergo molecular characterization to identify biomarkers that are critical for early cancer detection, prognosis, therapeutic assessment, and post-treatment monitoring. These innovative biosources exhibit characteristics analogous to those of the primary tumor from which they originate or interact. This review comprehensively explores the diverse technologies and methodologies employed for processing these biosources, along with their principal clinical applications.

Fibrinogen-fibrin degradation products (DR-70) are derived from tumor cells or metastases. Our previous study reported the diagnostic values in dogs with tumors, but no research has yet to be conducted to establish DR-70 as a prognostic marker. Herein, we investigated changes in DR-70 concentrations and disease courses in dogs with tumors. Overall survival time (OST) analysis was performed in 195 dogs with tumors, stratified with a recommended cut-off (1.514 µg/mL). Continual DR-70 measurements were performed during the medical interventions of 27 dogs with neoplasms. Clinical conditions and medical records were retrospectively reviewed. According to a cut-off value, dogs with plasma DR-70 concentrations above 1.514 µg/mL had shorter survival rates than those with concentrations below this threshold. In cases with complete or partial remission in response to treatment, the DR-70 concentration was decreased compared with that at the first visit, whereas it was increased in patients with disease progression. Our study suggested that changes in DR-70 concentration can be used as a prognostic biomarker for canine neoplasms. Furthermore, increased plasma DR-70 levels might be associated with shorter survival, and DR-70 concentrations may reflect responses to medical intervention.

Sensitive and selective detection of cancer biomarkers is crucial for early diagnosis and treatment of cancer, one of the most dangerous diseases in the world. Metal-organic frameworks (MOFs), a class of hybrid porous materials fabricated through the assembly of metal ions/clusters and organic ligands, have attracted increasing attention in the sensing of cancer biomarkers, due to the advantages of adjustable size, high porosity, large surface area and ease of modification. MOFs have been utilized to not only fabricate active sensing interfaces but also arouse a variety of measurable signals. Several representative analytical technologies have been applied in MOF-based biosensing strategies to ensure high detection sensitivity toward cancer biomarkers, such as fluorescence, electrochemistry, electrochemiluminescence, photochemistry and colorimetric methods. In this review, we summarized recent advances on MOFs-based biosensing strategies for the detection of cancer biomarkers in recent three years based on the categories of metal nodes, and aimed to provide valuable references for the development of innovative biosensing platform for the purpose of clinical diagnosis.

Introduction: In the dynamic landscape of modern healthcare, the ability to anticipate and diagnose diseases, particularly in cases where early treatment significantly impacts outcomes, is paramount. Cancer, a complex and heterogeneous disease, underscores the critical importance of early diagnosis for patient survival. The integration of metabolomics information has emerged as a crucial tool, complementing the genotype-phenotype landscape and providing insights into active metabolic mechanisms and disease-induced dysregulated pathways., Areas Covered: This review explores a decade of developments in the search for biomarkers validated within the realm of cancer studies. By critically assessing a diverse array of research articles, clinical trials, and studies, this review aims to present an overview of the methodologies employed and the progress achieved in identifying and validating biomarkers in metabolomics results for various cancer types., Expert Opinion: Through an exploration of more than 800 studies, this review has allowed to establish a general idea about state-of-art in the search of biomarkers in metabolomics studies involving cancer which include certain level of results validation. The potential for metabolites as diagnostic markers to reach the clinic and make a real difference in patient health is substantial, but challenges remain to be explored.

Objective: Patients previously examined for cancer with a negative result may present in general practice with ongoing or new symptoms or signs suggestive of cancer. This paper explores the potential existence of a relatively safe period for cancer occurrence after receiving negative examination results for specific types of cancer, including lung (CT thorax), upper gastrointestinal (gastroscopy), colorectal (colonoscopy), bladder (cystoscopy), and breast (clinical mammography)., Design: Register-based time-to-event analyses., Setting: Denmark., Subjects: All 3.3 million citizens aged 30-85 years who on January first, 2017, had not previously been diagnosed with the specific type of cancer were categorized based on the time since their most recent examination., Main Outcome Measures: Using 1-year follow-up, we calculated the age- and sex-adjusted hazard ratios of being diagnosed with the related cancer, with non-examined individuals as reference. Negative examination results were defined as the absence of a cancer diagnosis within 6 months following the examination., Results: Previous negative examination results were common, also among those diagnosed with cancer during follow-up. For 10 years after a negative colonoscopy the risk of diagnosing a colorectal cancer was nearly halved. However, already 1 year after a clinical mammography and 2 years after a CT thorax the risk of diagnosing the related cancers was significantly higher among those with a previous negative result compared to non-examined individuals., Conclusion: This study did not identify a post-examination period in which the cancer risk, compared to non-examined individuals, was sufficiently low to confidently rule out any of the investigated cancers.

Objective: Patients with psychiatric disorders are at risk of experiencing suboptimal cancer diagnostics and treatment. This study investigates how this patient group perceives the cancer diagnostic process in general practice., Design: Cross-sectional study using questionnaire and register data., Setting: General practice in Denmark., Subjects: Patients diagnosed with cancer in late 2016 completed a questionnaire about their experiences with their general practitioner (GP) in the cancer diagnostic process ( n  = 3411). Information on pre-existing psychiatric disorders was obtained from register data on psychiatric hospital contacts and primary care treated psychiatric disorders through psychotropic medications. Logistic regression was used to analyse the association between psychiatric disorders and the patients' experiences., Main Outcome Measures: Patients' experiences, including cancer worry, feeling being taken seriously, and the perceived time between booking an appointment and the first GP consultation.[Box: see text]., Results: A total of 13% of patients had an indication of a psychiatric disorder. This group more often perceived the time interval as too short between the first booking of a consultation and the first GP consultation. Patients with primary care treated psychiatric disorders were more likely to worry about cancer at the first presentation and to share this concern with their GP compared with patients without psychiatric disorders. We observed no statistically significant association between patients with psychiatric disorders and perceiving the waiting time to referral from general practice, being taken seriously, trust in the GP's abilities, and the patients' knowledge of the process following the GP referral., Conclusion: The patients' experiences with the cancer diagnostic process in general practice did not vary largely between patients with and without psychiatric disorders. Worrying about cancer may be a particular concern for patients with primary care treated psychiatric disorders.

Objective: Diagnosis of cancer is challenging in primary care due to the low incidence of cancer cases in primary care practice. A prolonged diagnostic interval may be due to doctor, patient or system factors, or may be due to the characteristics of the cancer itself. The objective of this study was to learn from Primary Care Physicians' (PCP) experiences of incidents when they had failed to think of, or act on, a cancer diagnosis., Design: A qualitative, online survey eliciting PCP narratives. Thematic analysis was used to analyse the data., Setting and Subjects: A primary care study, with narratives from 159 PCPs in 23 European countries., Main Outcome Measures: PCPs' narratives on the question 'If you saw this patient with cancer presenting in the same way today, what would you do differently?, Results: The main themes identified were: thinking broadly; improvement in communication and clinical management; use of other available resources and 'I wouldn't do anything differently'., Conclusion (implications): To achieve more timely cancer diagnosis, PCPs need to provide a long-term, holistic and active approach with effective communication, and to ensure shared decision-making, follow-up and continuing re-assessment of the patients' clinical conditions.

Aim: Next-generation sequencing (NGS) of solid tumors can inform treatment decisions; however, uptake remains low. This objective of this systematic review was to identify barriers to and facilitators of NGS in US oncology settings. Materials & methods: Embase and MEDLINE were searched in March 2023 for articles published from 2012 to 2023 on barriers and facilitators of NGS adoption for solid tumors. Surveys, interviews and observational studies were eligible. Studies on genetic testing for hereditary cancers and non-US studies were excluded. The Motheral scale, Joanna Briggs Institute critical appraisal checklist and McGill Mixed Methods Appraisal Tool were used to assess study quality. Data were synthesized narratively. Results: Twenty-one studies were included. Study participants were clinicians, payers and administrators. Key barriers included complex reimbursement processes and uncertainties around clinical utility. Including recommendations for NGS in clinical practice guidelines was a key facilitator, although insurance policies were often more restrictive than guideline recommendations. Conclusion: Uptake of NGS is increasing but barriers remain. Changes to the current reimbursement frameworks are needed to increase access to NGS. The impact of implementing the 2018 National Coverage Determination, which allows access to NGS for all Medicare beneficiaries with advanced cancer, is not yet evident in the published literature.

Reactive oxygen species (ROS) play an important role in living activities as signaling molecules that regulate the living activities of organisms. There are many types of ROS, mainly including hydrogen peroxide (H 2 O 2 ), hypochlorous acid (HOCl), hydroxyl radical (•OH), peroxyl radical (ROO•), singlet oxygen ( 1 O 2 ), peroxynitrite (ONOO - ) and superoxide anion radical (O 2 - •) etc. Existing studies have shown that changes in ROS levels are closely associated with the development of many diseases, such as inflammation, cancer, cardiovascular disease, and neurodegenerative damage. Small molecule fluorescent probes have been widely used in biology, pathology and medical diagnosis due to their advantages of noninvasive, high sensitivity and in vivo real-time detection. It is extremely important to better apply small-molecule fluorescent probes to detect ROS levels in organisms to achieve early diagnosis of diseases and assessment of therapeutic conditions. This work focuses on summarizing the representative applications of some fluorescent probes in ROS disease models in recent years. This article focuses on summarizing the construction methods of various ROS-related disease models, and classifying and analyzing the basic ideas and methods of fluorescent probes applied to disease models according to the characteristics of various diseases.

Aim: This study evaluates the prognostic significance of NOB1 expression levels in various cancers. Patients & methods: Studies examining NOB1 expression in cancer, encompassing data from 1694 patients across 14 studies, were analyzed for overall survival (OS) and progression-free survival (PFS) using hazard ratios (HRs) and 95% CIs, and for clinicopathological parameters using relative risks (RRs). Results: High NOB1 expression correlated with shorter OS (HR: 2.12, 95% CI: 1.82-2.48) and PFS (HR: 2.23, 95% CI: 1.62-3.07) and was associated with adverse tumor characteristics such as stage and metastasis. Conclusion: Elevated NOB1 expression in various tumors signifies a poor prognosis, serving as a predictive marker for malignancy outcomes. PROSPERO Register Number: CRD42023394051.

Enzymes have been used for disease diagnosis for many decades; however, advancements in technology like ELISA and flow cytometry-based detection have significantly increased their use and have increased the sensitivity of detection. Technological advancements in recombinant enzyme production have increased enzymatic stability, and the use of colorimetric-based and florescence-based assays has led to their increased use as biomarkers for disease detection. Enzymes like acid phosphatase, cathepsin, lactate dehydrogenase, thymidine kinase and creatine kinase are indispensable markers for diagnosing cancer, cardiovascular diseases and others. This minireview summarizes various enzymes used in disease diagnosis, their metabolic role, market value and potential as disease markers across various metabolic and other disorders.

Artificial intelligence (AI) has rapidly advanced in the past years, particularly in medicine for improved diagnostics. In clinical cytogenetics, AI is becoming crucial for analyzing chromosomal abnormalities and improving precision. However, existing software lack learning capabilities from experienced users. AI integration extends to genomic data analysis, personalized medicine and research, but ethical concerns arise. In this article, we discuss the challenges of the full automation in cytogenetic test interpretation and focus on its importance and benefits.

Although not as well studied as the bacterial component of the human microbiota, the commensal fungi or mycobiota play important roles in maintaining our health by augmenting our immune system. This mycobiota is also associated with various fatal diseases like opportunistic mycoses, and even cancer, with different cancers having respective type-specific mycobiota. The different fungal species which comprise these different intratumoral mycobiota play important roles in cancer progression. The aim of this review paper is to decipher the association between mycobiota and cancer, and shed light on new avenues in cancer diagnosis, and the development of new anti-cancer therapeutics.

Recent evidence has shown that the human microbiome is associated with various diseases, including cancer. The salivary microbiome, fecal microbiome, and circulating microbial DNA in blood plasma have all been used experimentally as diagnostic biomarkers for many types of cancer. The microbiomes present within local tissue, other regions, and tumors themselves have been shown to promote and restrict the development and progression of cancer, most often by affecting cancer cells or the host immune system. These microbes have also been shown to impact the efficacy of various cancer therapies, including radiation, chemotherapy, and immunotherapy. Here, we review the research advances focused on how microbes impact these different facets and why they are important to the clinical care of cancer. It is only by better understanding the roles these microbes play in the diagnosis, development, progression, and treatment of cancer, that we will be able to catch and treat cancer early.

I employed a Markov model to simulate outcomes for a cohort of 1,000 hypothetical patients, comparing improvements in early detection, side effect management, and palliative care over a ten-year period. This model showed benefits in early detection and proactive health management, improving disease stability and reducing mortality rates. This protocol resulted in an 85.8% five-year survival rate, compared to 69.5% under standard protocol. Cost-effectiveness analysis showed significantly reduced costs and improved quality-adjusted life years. Our findings underscore the importance of comprehensive cancer care. These improvements not only reduce simulated healthcare costs but also significantly improve patient outcomes.

Avoiding immune destruction and polymorphic microbiomes are two key hallmarks of cancer. The tumor microenvironment (TME) is essential for the development of solid tumors, and the function of tumor-associated macrophages (TAMs) in the TME is closely linked to tumor prognosis. Therefore, research on TAMs could improve the progression and control of certain tumor patients. Additionally, the intestinal flora plays a crucial role in metabolizing substances and maintaining a symbiotic relationship with the host through a complex network of interactions. Recent experimental and clinical studies have suggested a potential link between gut microbiome and TME, particularly in regulating TAMs. Understanding this association could improve the efficacy of tumor immunotherapy. This review highlights the regulatory role of intestinal flora on TAMs, with a focus on gut microbiota and their metabolites. The implications of this association for tumor diagnosis and treatment are also discussed, providing a promising avenue for future clinical treatment strategies.

Introduction: Exportin 1 (XPO1) is overexpressed in several solid tumors, and is associated with poor prognosis. Here, we aimed to evaluate the implication of XPO1 expression in solid tumors through a meta-analysis., Methods: PubMed, Web of Science, and Embase databases were searched for articles published until February 2023. Statistical data of the patients, odds ratios and hazard ratios (HRs), together with their corresponding 95% confidence intervals (CIs) were pooled to assess clinicopathological features and survival outcomes. Besides, the Cancer Genome Atlas (TCGA) was used to explore the prognostic significance of XPO1 in solid tumors., Results: A total of 22 works, comprising 2595 patients were included in this study. The results suggested that increased XPO1 expression was associated with a higher tumor grade, more lymph node metastasis, advanced tumor stage, and progressively worse total clinical stage. Additionally, high XPO1 expression was associated with worse overall survival (OS) (HR = 1.43, 95% CI = 1.12-1.81, P  = 0.004) and shorter progression-free survival (HR = 1.40, 95% CI = 1.07-1.84, P  = 0.01). An analysis using the TCGA dataset showed that high XPO1 expression was associated with poor OS and disease-free survival., Conclusions: XPO1 is a promising prognostic biomarker and may constitute a therapeutic target for solid tumors. PROSPERO registration number : CRD42023399159.

Background: Previous studies have shown that the differential expression of lncRNA NR2F1-AS1 is closely related to the prognosis of cancer, but the conclusion is still controversial. Therefore, we conducted a meta-analysis and bioinformatics analysis to explore the correlation between LncRNA NR2F1-AS1 and cancer prognosis., Methods: From the beginning to January 25, 2023, we searched for correlational studies on PubMed, Embase, the Cochrane Library, and Web of Science. We used pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) to determine the importance of LncRNA NR2F1-AS1 for survival and clinicopathological features of human cancers., Results: The meta-analysis of 637 patients in the 11 included articles showed that upregulation of LncRNA NR2F1-AS1 was associated with shorter overall survival (HR = 1.46,95%Cl 1.06-2.01, p  = 0.02) in cancer patients. In addition, overexpression of LncRNA NR2F1-AS1 predicted TNM tumor stage (OR = 3.37, 95%Cl 2.07-5.48, p  < 0.00001), and Distant metastasis (OR = 0.18, 95%Cl 0.06-0.48, p  = 0.0007). However, the difference in age (OR = 1.10,95%Cl 0.71-1.71, p  = 0.67), gender (OR = 1.26,95%Cl 0.79-2.00, p  = 0.34), Lymph node metastasis (OR = 1.44,95%Cl 0.27-7.80, p  = 0.67) or larger tumor size (OR = 1.56,95%Cl 0.48-5.08, p  = 0.46) was not statistically significant., Conclusion: Upregulation of LncRNA NR2F1-AS1 was associated with poor prognosis and advanced clinicopathologic features of tumor patients.

Introduction: Advances in genomics have facilitated the application of cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) in phase II and phase III clinical trials. The various mutations of cfDNA/ctDNA have been correlated with clinical features. Advances in next-generation sequencing (NGS) and digital droplet PCR have paved the way for identifying cfDNA/ctDNA mutations., Areas Covered: Herein, the biology of ctDNA and its function in clinical application in metastasis, which may lead to improved clinical management of metastatic cancer patients, are comprehensively reviewed., Expert Opinion: Metastatic cancer ctDNA shows the greatest frequency of mutations in TP53, HER-2, KRAS, and EGFR genes (alteration frequency of > 50%). Therefore, identifying key mutations frequently present in metastatic cancers can help identify patients with pre-malignant tumors before cancer progression. Studying ctDNA can help determine the prognosis and select appropriate treatments for affected patients. Nevertheless, the obstacles to detecting and analyzing ctDNA should be addressed before translation into routine practice. Also, more clinical trials should be conducted to study the significance of ctDNA in commonly diagnosed malignancies. Given the recent advances in personalized anti-neoplastic treatments, further studies are needed to detect a panel of ctDNA and patient-specific ctDNA for various cancers.

Background: The autophagy-associated transmembrane protein EI24 is associated with cancer growth and patient survival. We aimed to explore the prognostic role and immune infiltration characteristics of EI24 at a pan-cancer level., Methods: We collected data from multiple databases to explore the expression and prognostic role of EI24 in various cancers. Correlations between EI24 expression and DNA methylation, RNA modification, tumor mutation burden (TMB), microsatellite instability (MSI), immune moderator, immune checkpoint-related genes, the tumor immune microenvironment, and clinicopathological characteristics were analyzed. Finally, immunohistochemistry and western blotting were performed to validate the protein levels of EI24 in different tumors., Results: Differential expression of EI24 was observed in most cancer types compared to non-cancerous tissues. EI24 showed a significant association with prognosis and may represent a new indicator of prognosis in patients with cancer. In most cancers, EI24 is closely associated with tumor immunity and interacts with various immune cells. Moreover, significant correlations were observed between EI24 expression and RNA modification, TMB, MSI, immune moderators, and immune checkpoint-related genes., Conclusion: This study provides new insights into the functions and clinical value of EI24 in different tumors and suggests that EI24 may serve as a promising biomarker or therapeutic target for cancer management.

Objective: To observe the prognostic value of circular RNA mitochondrial tRNA translation optimization 1 (circMTO1) in human tumors., Methods: We searched multiple databases for related reports published before November 01, 2021. The OR/HR and 95% CI were extracted to explore the correlation between circMTO1 expression and clinicopathological features in various cancers. The stability of the results from meta-analysis was estimated via sensitivity analysis. We adopted Begg's funnel plots and Egger's test to appraise the potential bias of publication. Subgroup analysis for overall survival (OS) were also performed., Results: 11 studies containing 1383 patients and 4 articles including 536 patients were enrolled. We found that low expression status of circMTO1 was significantly related to big tumor size (OR=2.11, 95% CI: 1.26-3.56, P<0.05), poor differentiation tumors (OR=2.09, 95% CI: 1.46-2.98, P<0.05), OS (HR=2.02, 95% CI: 1.63-2.50, P<0.05), disease-free survival (DFS) (HR=1.83, 95% CI: 1.27-2.56, P<0.05) of cancers. Subgroup analysis indicated that low expression status of circMTO1 was correlated with OS, regardless of analysis method, cut-off value, case number and NOS score., Conclusions: The low expression of circMTO1 may predict big tumor size, poor differentiation and worse outcome of cancer, presenting that circMTO1 may be a useful biomarker for prognosis of tumors.

For cancers and other pathologies, early diagnosis remains the most promising path to survival. Profiling of longitudinal cohorts facilitates insights into trajectories of biomarkers. We measured microRNA expression in 240 serum samples from patients with colon, lung, and breast cancer and from cancer-free controls. Each patient provided at least two serum samples, one prior to diagnosis and one following diagnosis. The median time interval between the samples was 11.6 years. Using computational models, we evaluated the circulating profiles of 21 microRNAs. The analysis yielded two sets of biomarkers, static ones that show an absolute difference between certain cancer types and controls and dynamic ones where the level over time provided higher diagnostic information content. In the first group, miR-99a-5p stands out for all three cancer types. In the second group, miR-155-5p allows to predict lung cancers and colon cancers. Classification in samples from cancer and non-cancer patients using gradient boosted trees reached an average accuracy of 79.9%. The results suggest that individual change over time or an absolute value at one time point may predict a disease with high specificity and sensitivity.

Aim: In January 2017, a new funding model for diagnostic genetic testing in cancer was introduced in Poland., Objectives: The aim of this study was to assess the impact of changing the funding model for genetic diagnosis in oncology on improving access to personalized medicine in Poland between 2017 and 2019., Methods: The analysis included data on settlements with the National Health Fund for genetic tests in cancer under a contract of the hospital treatment type and under the contract in the type of separately contracted services between 2017 and 2019., Results: The 150,647 diagnostic genetic tests were reported, which were billed to 111,872 patients. The average number of tests per patient was 1.35. One test was billed to 83.5% of patients, 11.2% of patients had two tests billed, and 5.3% had at least three tests billed. The number of services provided under the hospital treatment contract in 2018 doubled compared to the previous year. For separately contracted services, more than threefold increase in genetic testing performed in 2019 compared to 2018 was observed., Conclusion: our data show that the novel funding model for genetic services introduced in Poland has positive impact on the availability of genetic testing for patients.

This review surveys Infrared, Raman/SERS and Brillouin spectroscopies for medical diagnostics and detection of biomarkers in biofluids, that include urine, blood, saliva and other biofluids. These optical sensing techniques are non-contact, noninvasive and relatively rapid, accurate, label-free and affordable. However, those techniques still have to overcome some challenges to be widely adopted in routine clinical diagnostics. This review summarizes and provides insights on recent advancements in research within the field of vibrational spectroscopy for medical diagnostics and its use in detection of many health conditions such as kidney injury, cancers, cardiovascular and infectious diseases. The six comprehensive tables in the review and four tables in supplementary information summarize a few dozen experimental papers in terms of such analytical parameters as limit of detection, range, diagnostic sensitivity and specificity, and other figures of merits. Critical comparison between SERS and FTIR methods of analysis reveals that on average the reported sensitivity for biomarkers in biofluids for SERS vs FTIR is about 10 3 to 10 5 times higher, since LOD SERS are lower than LOD FTIR by about this factor. High sensitivity gives SERS an edge in detection of many biomarkers present in biofluids at low concentration (nM and sub nM), which can be particularly advantageous for example in early diagnostics of cancer or viral infections.HighlightsRaman, Infrared spectroscopies use low volume of biofluidic samples, little sample preparation, fast time of analysis and relatively inexpensive instrumentation.Applications of SERS may be a bit more complicated than applications of FTIR (e.g., limited shelf life for nanoparticles and substrates, etc.), but this can be generously compensated by much higher (by several order of magnitude) sensitivity in comparison to FTIR.High sensitivity makes SERS a noninvasive analytical method of choice for detection, quantification and diagnostics of many health conditions, metabolites, and drugs, particularly in diagnostics of cancer, including diagnostics of its early stages.FTIR, particularly ATR-FTIR can be a method of choice for efficient sensing of many biomarkers, present in urine, blood and other biofluids at sufficiently high concentrations (mM and even a few µM)Brillouin scattering spectroscopy detecting visco-elastic properties of probed liquid medium, may also find application in clinical analysis of some biofluids, such as cerebrospinal fluid and urine.

Introduction: The pursuit of easy-to-use, non-invasive and inexpensive diagnostics is an urgent task for clinicians and scientists. Saliva is an important component of body fluid with regular changes of contents under various pathophysiological conditions, and the biomarkers identified from saliva shows high application potentials and values in disease diagnostics. This review introduces the latest developments in saliva research, with an emphasis on the detection and application of salivary biomarkers in cancer detection., Areas Covered: Detection of disease-specific biomarkers in saliva samples by existing salivaomic methods can be used to diagnose various human pathological conditions and was introduced in details. This review also covers the saliva collection methods, the analytical techniques as well as the corresponding commercial products, with an aim to describe an holistic process for saliva-based diagnostics., Expert Opinion: Saliva, as a non-invasive and collectable body fluid, can reflect the pathophysiological changes of the human body to a certain extent. Identification of reliable saliva biomarkers can provide a convenient way for cancer detection in clinical applications.

Background: Peripheral morphological abnormalities play important roles in the early diagnosis and prognosis of the COVID-19 infection. The aim of the present study was to assess the morphological alterations in the peripheral blood (PB) cells in patients with COVID-19 infection, with special attention to a different group of atypical lymphocytes that had been observed in the PB of COVID-19 cancer and non-cancer patients., Methods: The PB cells were examined in 84 COVID-19 positive cancer patients, and 20 COVID-19 positive non-cancer patients, compared to 30 healthy normal controls. The data were correlated to the disease severity, patients' clinicopathological features, and outcomes., Results: There was an increased incidence of giant platelets, neutrophils shifting left, and abnormal monocytes in the COVID-19 positive cancer and non-cancer patients compared to the control group ( P  < .001, P  < .001 and P  = .014; respectively). Neutrophils with abnormal toxic granulations, Pseudo Pelger-Heut abnormality, and reactive lymphocytes were significantly increased in COVID-19 cancer patients compared to COVID-19 non-cancer patients and the control group ( P  = .001, P  < .001, and P  < .001; respectively). An abnormal form of lymphocytes' morphological changes (Covicytes) was significantly detected in COVID-19 cancer patients [60.7% (51/84)], and in COVID-19 non-cancer patients [55% (11/20)], while it was absent in the normal controls [0.0% (0/30), P  < 0.001]. The presence of the Covicytes is associated significantly with a better prognosis in cancer and non-cancer COVID-19 patients., Conclusion: Covicytes could be a useful marker supporting the diagnosis of SARS-COV-2 infection, and it is associated with a favorable prognosis.

Introduction: Paternal uniparental disomy of chromosome 11 (upd(11)pat) accounts for up to 20% of molecularly confirmed Beckwith-Wiedemann spectrum (BWSp) cases. It belongs to the BWSp subgroup with the second highest tumor risk, and therefore needs particular awareness in research, diagnostics and clinical management., Areas Covered: We overview the contribution of paternal (mosaic) uniparental disomy of chromosome 11 (UPD, upd(11)pat) and mosaic paternal uniparental diploidy in patients with Beckwith-Wiedemann features. The review comprises the current knowledge on their formation and their molecular and clinical consequences. Accordingly, the consequences for diagnostic testing and clinical monitoring are compiled., Expert Opinion: The necessity to diagnostically identify and thus discriminate genome-wide paternal uniparental disomy, and upd(11)pat becomes obvious, due to the differences in the clinical course, disease prognosis, and treatment. In particular, monitoring of tumor development by liquid biopsy might be a promising option in the future. From the research point of view, it should be addressed why 11p is prone to mitotic recombination and thus also provide to the role of upd(11) as second hit in tumorigenesis.

Background: Previous studies have reported the prognostic value of p53 upregulated modulator of apoptosis (PUMA) in numerous human tumors, but the conclusions have not been consistent. Therefore, this meta-analysis and the Cancer Genome Atlas (TCGA) data analysis were performed to estimate the prognostic significance of PUMA in solid tumors., Research Design and Methods: A search was conducted in PubMed, Embase, Web of Science, Cochrane Library and CNKI up to 21 July 2022. In total, 10 studies with 2,207 patients were included. We extracted the overall survival (OS) and disease-free survival (DFS) data. The hazard ratios (HRs) and 95% confidence intervals (95% CI) were adopted for evaluating the association., Results: Decreased PUMA expression was significantly associated with worse OS (HR = 0.54, 95% CI = 0.38-0.78) and worse DFS (HR = 0.54, 95% CI = 0.42-0.70). Subgroup analysis showed that the prognostic role of PUMA for OS was most significant in the digestive system (HR = 0.52, 95% CI = 0.38-0.69). Furthermore, the expression of PUMA was not affected by tumor differentiation or clinical stage, and TCGA dataset analysis confirmed these results., Conclusions: We proved that expression of PUMA may serve as an independent prognostic factor for patients with solid tumors.

The identification and quantification of predictive biomarkers characterize personalized medicine approaches and patient-centric clinical development. In practice, the sponsor needs evaluating whether biomarker-informed clinical development strategies are more likely to benefit current and future patients. To this end, a simple metric is proposed and assessed here quantifying the expected clinical benefit (ECB) of clinical development programmes. Using simulation scenarios and endpoints relevant to oncology, the ECB of a simple biomarker-informed strategy is shown to be specific and sensitive. Also, the ECB difference is shown to increase in the biomarker-driven incremental efficacy and with the population prevalence of biomarker-positive study participants.

Malignant tumors are a threat to human health, thus it is critical to better understand the mechanism of tumor occurrence and development and to find key therapeutic targets. Competitive endogenous RNA (ceRNA) is a type of RNA molecule that includes mRNA of coding-protein, pseudogenes, long non-coding RNA (lncRNA), and circular RNA (circRNA) etc. It is created through a competitive combination of common small RNA (miRNA) and has an inhibitory effect on mRNA translation. ceRNA regulate the post transcriptional expression of genes by competitively binding to common microRNAs (miRNAs).Studies have shown that cernas are involved in tumor cell proliferation, invasion and migration, drug resistance, angiogenesis, as well as tumor immunity, and so on, affecting the progression of tumor development. This article reviews the reported roles of exosomal ceRNA in the diagnosis and treatment of malignant tumors and the mechanisms underlying these.

This multi-center cohort-study examined late mortality among 6,165 Dutch five-year childhood cancer survivors diagnosed 1963-2001. Clinical details and cause of death were based on medical records. Mortality was 12-fold that of the general population, with 51.3 additional deaths per 10,000 person-years (21.9 yrs median follow-up). Cumulative mortality 15 yrs post-diagnosis was 6.9%, predominantly from late recurrences; thereafter the absolute contribution of other health outcomes increased. Cumulative all-cause and recurrence-related mortality were highest for Central Nervous System and bone tumor survivors. All-cause, but not subsequent tumor and circulatory disease-related cumulative mortality, was highest for patients diagnosed 1963-1979 vs. later ( p -trend <0.001).

Introduction: Diseases were initially thought to be the consequence of a single gene mutation. Advances in DNA sequencing tools and our understanding of gene behavior have revealed that complex diseases, such as cancer, are the product of genes cooperating with each other and with their environment in orchestrated communication networks. Seeing that the function of individual genes is still used to analyze cancer, the shift to using functionally interacting groups of genes as a new unit of study holds promise for demystifying cancer., Areas Covered: The literature search focused on three types of cancer, namely breast, lung, and prostate, but arguments from other cancers were also included. The aim was to prove that multigene analyses can accurately predict and prognosticate cancer risk, subtype cancer for more personalized and effective treatments, and discover anti-cancer therapies. Computational intelligence is being harnessed to analyze this type of data and is proving indispensable to scientific progress., Expert Opinion: In the future, comprehensive profiling of all kinds of patient data (e.g. serum molecules, environmental exposures) can be used to build universal networks that should help us elucidate the molecular mechanisms underlying diseases and provide appropriate preventive measures, ensuring lifelong health and longevity.

Introduction: Adaptations of eukaryotic cells to environmental changes are important for their survival. However, under some circumstances, microenvironmental changes promote that eukaryotic cells utilize a metabolic signature resembling a unicellular organism named the Warburg effect. Most cancer cells share the Warburg effect displaying lactic fermentation and high glucose uptake. The Warburg effect also induces a metabolic rewiring stimulating glutamine consumption and lipid synthesis, also considered cancer hallmarks. Amino acid metabolism alteration due to the Warburg effect increases plasma levels of proline and branched-chain amino acids in several cancer types. Proline and lipids are probably used as electron transfer molecules in carcinogenic cells. In addition, branched-chain amino acids fuel the Krebs cycle, protein synthesis, and signaling in cancer cells., Areas Covered: This review covers how metabolomics studies describe changes in some metabolites and proteins associated with the Warburg effect and related metabolic pathways., Expert Opinion: In this review, we analyze the metabolic signature of the Warburg effect and related phenotypes and propose some Warburg effect-related metabolites and proteins (lactate, glucose uptake, glucose transporters, glutamine, branched-chain amino acids, proline, and some lipogenic enzymes) as promising cancer biomarkers.

Introduction: Hereditary cancer predisposition syndromes are caused by germline pathogenic or likely pathogenic variants in cancer predisposition genes (CPG). The majority of pathogenic variants in CPGs are point mutations, but large gene rearrangements (LGRs) are present in several CPGs. LGRs can be much more difficult to characterize and perhaps they may have been neglected in molecular diagnoses., Areas Covered: We aimed to evaluate the frequencies of germline LGRs in studies conducted in different populations worldwide through a qualitative systematic review based on an online literature research in PubMed. Two reviewers independently extracted data from published studies between 2009 and 2020. In total, 126 studies from 37 countries and 5 continents were included in the analysis. The number of studies in different continents ranged from 3 to 48 and for several countries there was an absolute lack of information. Asia and Europe represented most of the studies, and LGR frequencies varied from 3.04 to 15.06% in different continents. MLPA was one of the methods of choice in most studies (93%)., Expert Opinion: The LGR frequencies found in this review reinforce the need for comprehensive molecular testing regardless of the population of origin and should be considered by genetic counseling providers.

Secreted phosphoprotein 1 ( SPP1 ) is involved in immune regulation, cell survival, and tumor progression. Studies have demonstrated that SPP1 plays an important role in certain individual tumors. However, the expression profile and oncogenic features of SPP1 in diverse cancers are remaining unknown. Therefore, we performed a comprehensive analysis using The Cancer Genome Atlas (TCGA) database. Raw data of 33 cancer types were download from the University of California Santa Cruz (UCSC) Xena website. The expression of SPP1 and its relationship with tumor prognosis, immune invasion, tumor microenvironment, and immunotherapy were analyzed using the R language. The function analysis was conducted using Gene Set Enrichment Analysis (GSEA). The oncogenic features of SPP1 was validated by wound-healing assay and EdU staining assay. SPP1 highly expressed in most cancers. The expression of SPP1 was significant related to prognosis, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoint genes, suggested that SPP1 plays an essential role in the tumor immune microenvironment and immune cell infiltration. The immune/stromal scores correlated positively with the SPP1 expression, and the relationship was affected by tumor heterogeneity and immunotherapy. In addition, SPP1 could predict the response of tumor immunotherapy. Functional analysis revealed the SPP1 -associated terms and pathways. Finally, SPP1 significantly elevated cell proliferation and migration in A549, Huh7, HT-29, A2780 tumor cell lines. In conclusion, this study indicated that SPP1 involved in tumorigenesis, tumor progression, and regulated tumor immune microenvironment, revealing SPP1 might be a potential target for evaluating prognosis and immunotherapy in multiple cancers.

Non-invasive, immuno-dynamic, biomarkers positioned in cancer patient's blood milieu with immuno-oncological applications are rare. We recently established a "first-in-class" serum functional immunodynamics status (sFIS) assay, wherein in vitro assessment of serum-induced myeloid NFkB and/or interferon (IFN) response-signaling can be performed to "mimic" in situ patient's serum immune-biology. This modality has clear implications for anticipating patient prognosis and immunotherapy-relevant stratification., Competing Interests: The sFIS assay is currently the subject of an ongoing PCT patent application., (© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Background: Routine health checkup is an essential strategy for monitoring population health and maintaining healthy workforces. However, there was a lack of cancer screening tests among routine health checkups due to high costs and unreliable methods., Methods: We conducted a two-stage study to evaluate the value of a blood test, Cancer Differentiation Analysis (CDA TM ), which is developed to differentiate the blood samples of healthy individuals from those of cancer patients through measuring and analyzing multiple biophysical properties., Results: The first stage of a cross-sectional study included 75,942 healthy individuals in routine health checkup, and the second stage of a prospective population-based cohort included 1,957 healthy community members. Forty-eight and ten cancer cases were identified among cross-sectional study and prospective population-based cohort, respectively. Using a pre-determined cutoff, we found that the CDA™ test could differentiate blood samples between healthy and cancer individuals with >93% specificity and >55% sensitivity in both studies., Conclusions: With high specificity and moderate sensitivity of CDA™ test, our study indicates that we can analyze biophysical properties in the blood to rapidly and reliably screen healthy individuals from cancer patients in a health checkup setting where most individuals are healthy or with average risk of cancer.

Exosomes, small vesicles with the diameters of 40-160 nm, play an important role in intercellular transport and communication. Exosomes are rich in many kinds of biomolecules, and differential expression of exosomal contents directly reflects the state of the original cells. Therefore, the tumor exosomes are appearing as promising biomarkers in liquid biopsy, and highly sensitive and specific detection of tumor exosomes may provide the information for the early diagnosis, real-time monitoring and treatment of the tumors. In this review, we summarized the recent advances in the detection of tumor exosomes, mainly focusing on the use of different analytical techniques, such as optical and electrochemical methods as well as that combination with newly-emerging microfluidic techniques, thereby providing valuable information for the application in the clinical diagnosis and management of the tumors.

The contribution of DNA-methylation based gene silencing to carcinogenesis is well established. Increasingly, DNA-methylation is examined using genome-wide techniques, with recent public efforts yielding immense data sets of diverse malignancies representing the vast majority of human cancer related disease burden. Whereas mutation events may group preferentially or in high frequency with a given histology, mutations are poor classifiers of tumour type. Here we examine the hypothesis that cancer-specific DNA-methylation reflects the tissue of origin or carcinogenic risk factor, and these methylation abnormalities may be used to faithfully classify tumours according to histology. We present an analysis of 7427 tumours representing 19 human malignancies and 708 normal samples demonstrating that specific tumour changes in methylation can correctly determine site of origin and tumour histology with 86% overall accuracy. Examination of misclassified tumours reveals underlying shared biology as the source of misclassifications, including common cell of origin or risk factors.

Many cancer-related deaths are reported annually due to a lack of appropriate diagnosis and treatment strategies. Microfluidic technology, as new creativity has a great impact on automation and miniaturization via handling a small volume of materials and samples (in microliter to femtoliter range) to set up the system. Microfluidic devices not only detect various cancer-diagnostic factors from biological fluids but also can produce proper nanoparticles for drug delivery. With the contribution of microfluidics; multiple treatments for cancer such as chemotherapy, radiation therapy, and gene delivery can be implemented and studied. Hence, Microfluidics can be worth for the cancer field because of its high Throughput, high sensitivity, less material use, and low expense. In this review study, we intend to look at positive microfluidics prospects, features, benefits, and clinical applications.

Introduction: Cancer as one of the most common causes of death has always been one of the major health challenges globally. Since, the identification of tumors in the early tumor stages can significantly reduce mortality rates; it is required to introduce novel early detection tumor markers. MicroRNAs (miRNAs) have pivotal roles in regulation of cell proliferation, migration, apoptosis, and tumor progression. Moreover, due to the higher stability of miRNAs than mRNAs in body fluids, they can be considered as non-invasive diagnostic or prognostic markers in cancer patients., Areas Covered: In the present review we have summarized the role of miR-217 during tumor progressions. The miR-217 functions were categorized based on its target molecular mechanisms and signaling pathways., Expert Opinion: It was observed that miR-217 mainly exerts its function by regulation of the transcription factors during tumor progressions. The WNT, MAPK, and PI3K/AKT signaling pathways were also important molecular targets of miR-217 in different cancers. The present review clarifies the molecular biology of miR-217 and paves the way of introducing miR-217 as a non-invasive diagnostic marker and therapeutic target in cancer therapy.

Tumor glycolysis is a major promoter of carcinogenesis and cancer progression. Given its complex mechanisms and interactions, comprehensive analysis is needed to reveal its clinical significance and molecular features. On the basis of a well-established glycolysis gene expression signature, we quantified 8633 patients with different cancer types from the Cancer Genome Atlas (TCGA) and evaluated their prognostic associations. High tumor glycolytic activity correlated with inferior overall survival in the pan-cancer patients (hazard ratio: 1.70, 95% confidence interval: 1.20-2.40, P = 0.003). The prognostic value of glycolysis correlated with the molecular subtypes and was stable regardless of clinical parameters. The prognostic significance of glycolysis was validated using three independent datasets. In addition, genome, transcriptome, and proteome profiles were utilized to characterize the distinctive molecular features associated with glycolysis. Mechanistically, glycolysis fulfilled the fundamental needs of tumor proliferation in multiple ways. Exploration of the relationships between glycolysis and tumor-infiltrating immune cells showed that glycolysis enabled the immune evasion of tumor cells. Mammalian target of rapamycin (mTOR) inhibitors and dopamine receptor antagonists can effectively reverse the glycolytic status of cancers. Overall, our study provides an in-depth molecular understanding of tumor glycolysis and may have practical implications for clinical cancer therapy.

The study aimed to evaluate the prognostic value of CD169 expression in tumor-infiltrating macrophages from regional lymph nodes (RLN) in various tumors. In order to identify eligible articles, PubMed, EMBASE, Web of Science, and Cochrane Library were used to conduct a systematic search. Pooled hazard ratios (HRs) or odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were adopted to assess the relationship between CD169 expression and overall survival (OS) and clinicopathological characteristics. Ten studies, including eleven cohorts with 1699 patients, were enrolled. We found that high CD169 + expression in tumor-infiltrating macrophages from RLN was associated with a favorable OS (HR = 0.56, 95%CI: 0.39-0.79, P = 0.001). Subgroup analysis showed that high CD169+ expression had more predictive power in digestive system tumors (HR = 0.52, 95%CI: 0.42-0.67, <0.001). In addition, high CD169 expression was significantly linked with lymph node metastasis (OR = 0.66, 95%CI: 0.47-0.94, P = 0.020) and TNM stage (OR = 0.62, 95%CI: 0.48-0.80, P < 0.001). High CD169 expression in tumor-infiltrating macrophages from RLN was correlated with favorable survival outcome in patients with malignancies. CD169 may be a novel and effective prognostic marker, especially for digestive system tumors.