MicroRNAs as potential biomarkers for diagnosis of schizophrenia and influence of antipsychotic treatment

Chara cterized by positive symptoms(such as changes in behavior or thoughts,including delusions and hallu cinations),negative symptoms(such as apathy,anhedonia,and social withdrawal),and cognitive impairments,schizophrenia is a chro nic,severe,and disabling mental disorder with late adolescence or early adulthood onset,Antipsychotics are the most commonly used drugs to treat schizophrenia,but those currently in use do not fully reverse all three types of symptoms characte rizing this condition.Schizophrenia is frequently misdiagnosed,resulting in a delay of or inappropriate treatment.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of schizophrenia.The recent studies reviewed included microRNA profiling in blood-and urine-based materials and nervous tissue mate rials.From the studies that had validated the preliminary findings,potential candidate biomarkers for schizophrenia in adults could be miR-22-3p,-30e-5p,-92a-3p,-148b-5p,-181a-3p,-181a-5p,-181b-5p,-199 b-5p,-137 in whole blood,and miR-130b,-193a-3p in blood plasma.Antipsychotic treatment of schizophrenia patients was found to modulate the expression of certain microRNAs including miR-130b,-193a-3p,-132,-195,-30e,-432 in blood plasma.Further studies are warranted with adolescents and young adults having schizophrenia and consideration should be given to using animal models of the disorder to investigate the effect of suppressing or overexpressing specific microRNAs.

MicroRNAs as potential biomarkers for diagnosis of post-traumatic stress disorder

Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life events.Currently,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with and without post-traumatic stress disorder.In addition,the heterogeneity of clinical presentations of post-traumatic stress disorder and the overlap of symptoms with other conditions can lead to misdiagnosis and inappropriate treatment.Evidence suggests that this condition is a multisystem disorder that affects many biological systems,raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress disorder.We performed a PubMed search for microRNAs(miRNAs)in post-traumatic stress disorder(PTSD)that could serve as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December 2023.These included four studies with whole blood,seven with peripheral blood mononuclear cells,four with plasma extracellular vesicles/exosomes,and one with serum exosomes.One of these studies had also used whole plasma.Two studies were excluded as they did not involve microRNA biomarkers.Most of the studies had collected samples from adult male Veterans who had returned from deployment and been exposed to combat,and only two were from recently traumatized adult subjects.In measuring miRNA expression levels,many of the studies had used microarray miRNA analysis,miRNA Seq analysis,or NanoString panels.Only six studies had used real time polymerase chain reaction assay to determine/validate miRNA expression in PTSD subjects compared to controls.The miRNAs that were found/validated in these studies may be considered as potential candidate biomarkers for PTSD and include miR-3130-5p in whole blood;miR-193a-5p,-7113-5p,-125a,-181c,and-671-5p in peripheral blood mononuclear cells;miR-10b-5p,-203a-3p,-4488,-502-3p,-874-3p,-5100,and-7641 in plasma extracellular vesicles/exosomes;and miR-18a-3p and-7-1-5p in blood plasma.Several important limitations identified in the studies need to be taken into account in future studies.Further studies are warranted with war veterans and recently traumatized children,adolescents,and adults having PTSD and use of animal models subjected to various stressors and the effects of suppressing or overexpressing specific microRNAs.

MicroRNAs as potential biomarkers for diagnosis of attention deficit hyperactivity disorder

Inappropriate levels of hyperactivity,impulsivity,and inattention characterize attention deficit hyperactivity disorder,a common childhood-onset neuropsychiatric disorder.The cognitive function and learning ability of children with attention deficit hyperactivity disorder are affected,and these symptoms may persist to adulthood if they are not treated.The diagnosis of attention deficit hyperactivity disorder is only based on symptoms and objective tests for attention deficit hyperactivity disorder are missing.Treatments for attention deficit hyperactivity disorder in children include medications,behavior therapy,counseling,and education services which can relieve many of the symptoms of attention deficit hyperactivity disorder but cannot cure it.There is a need for a molecular biomarker to distinguish attention deficit hyperactivity disorder from healthy subjects and other neurological conditions,which would allow for an earlier and more accurate diagnosis and appropriate treatment to be initiated.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of attention deficit hyperactivity disorder.The recent studies reviewed had performed microRNA profiling in whole blood,white blood cells,blood plasma,and blood serum of children with attention deficit hyperactivity disorder.A large number of microRNAs were dysregulated when compared to healthy controls and with some overlap between individual studies.From the studies that had included a validation set of patients and controls,potential candidate biomarkers for attention deficit hyperactivity disorder in children could be miR-140-3p,let-7g-5p,-30e-5p,-223-3p,-142-5p,-486-5p,-151a-3p,-151a-5p,and-126-5p in total white blood cells,and miR-4516,-6090,-4763-3p,-4281,-4466,-101-3p,-130a-3p,-138-5p,-195-5p,and-106b-5p in blood serum.Further studies are warranted with children and adults with attention deficit hyperactivity disorder,and consideration should be given to utilizing rat models of attention deficit hyperactivity disorder.Animal studies could be used to confirm microRNA findings in human patients and to test the effects of targeting specific microRNAs on disease progression and behavior.

Marker Ki-67 is a potential biomarker for the diagnosis and prognosis of prostate cancer based on two cohorts

BACKGROUND Prostate cancer(PCa)is a widespread malignancy,predominantly affecting elderly males,and current methods for diagnosis and treatment of this disease continue to fall short.The marker Ki-67(MKI67)has been previously demonstrated to correlate with the proliferation and metastasis of various cancer cells,including those of PCa.Hence,verifying the association between MKI67 and the diagnosis and prognosis of PCa,using bioinformatics databases and clinical data analysis,carries significant clinical implications.AIM To explore the diagnostic and prognostic efficacy of antigens identified by MKI67 expression in PCa.METHODS For cohort 1,the efficacy of MKI67 diagnosis was evaluated using data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.For cohort 2,the diagnostic and prognostic power of MKI67 expression was further validated using data from 271 patients with clinical PCa.RESULTS In cohort 1,MKI67 expression was correlated with prostate-specific antigen(PSA),Gleason Score,T stage,and N stage.The receiver operating characteristic(ROC)curve showed a strong diagnostic ability,and the Kaplan-Meier method demonstrated that MKI67 expression was negatively associated with the progression-free interval(PFI).The time-ROC curve displayed a weak prognostic capability for MKI67 expression in PCa.In cohort 2,MKI67 expression was significantly related to the Gleason Score,T stage,and N stage;however,it was negatively associated with the PFI.The time-ROC curve revealed the stronger prognostic capability of MKI67 in patients with PCa.Multivariate COX regression analysis was performed to select risk factors,including PSA level,N stage,and MKI67 expression.A nomogram was established to predict the 3-year PFI.CONCLUSION MKI67 expression was positively associated with the Gleason Score,T stage,and N stage and showed a strong diagnostic and prognostic ability in PCa.

Soluble ST2:A Novel Biomarker for Diagnosis and Prognosis of Cardiovascular Disease

The increasing incidence of cardiovascular disease(CVD)is a significant global health concern,affecting millions of individuals each year.Accurate diagnosis of acute CVD poses a formidable challenge,as misdiagnosis can significantly decrease patient survival rates.Traditional biomarkers have played a vital role in the diagnosis and prognosis of CVDs,but they can be influenced by various factors,such as age,sex,and renal function.Soluble ST2(sST2)is a novel biomarker that is closely associated with different CVDs.Its low reference change value makes it suitable for continuous measurement,unaffected by age,kidney function,and other confounding factors,facilitating risk stratification of CVDs.Furthermore,the combination of sST2 with other biomarkers can enhance diagnostic accuracy and prognostic value.This review aims to provide a comprehensive overview of sST2,focusing on its diagnostic and prognostic value as a myocardial marker for different types of CVDs and discussing the current limitations of sST2.

Dysregulated microRNAs as a biomarker for diagnosis and prognosis of hepatitis B virus-associated hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a malignancy with a high incidence and fatality rate worldwide.Hepatitis B virus(HBV)infection is one of the most important risk factors for its occurrence and development.Early detection of HBV-associated HCC(HBV-HCC)can improve clinical decision-making and patient outcomes.Biomarkers are extremely helpful,not only for early diagnosis,but also for the development of therapeutics.MicroRNAs(miRNAs),a subset of non-coding RNAs approximately 22 nucleotides in length,have increasingly attracted scientists’attention due to their potential utility as biomarkers for cancer detection and therapy.HBV profoundly impacts the expression of miRNAs potentially involved in the development of hepatocarcinogenesis.In this review,we summarize the current progress on the role of miRNAs in the diagnosis and treatment of HBV-HCC.From a molecular standpoint,we discuss the mechanism by which HBV regulates miRNAs and investigate the exact effect of miRNAs on the promotion of HCC.In the near future,miRNA-based diagnostic,prognostic,and therapeutic applications will make their way into the clinical routine.

MicroRNAs as potential diagnostic biomarkers for bipolar disorder

Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had validated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observed in manic patients compared to controls, and dysregulation of miR-134,-152,-607,-633,-652,-155 occurred in euthymic patients compared to controls. Finally, microRNAs such as miR-34a,-34b,-34c,-137, and-140-3p,-21-3p,-30d-5p,-330-5p,-378a-5p,-134,-19b-3p were shown to have diagnostic potential in distinguishing bipolar disorder patients from schizophrenia or major depressive disorder patients, respectively. Further studies are warranted with adolescents and young adults having bipolar disorder and consideration should be given to using animal models of the disorder to investigate the effects of suppressing or overexpressing specific microRNAs.

Novel blood-based microRNA biomarker panel for early diagnosis of pancreatic cancer

AIM:To develop a panel of blood-based diagnostic biomarkers consisting of circulating microRNAs for the detection of pancreatic cancer at an early stage.METHODS:Blood-based circulating microRNAs were profiled by high throughput screening using microarray analysis,comparing differential expression between early stage pancreatic cancer patients(n = 8) and healthy controls(n = 11).A panel of candidate microRNAs was generated based on the microarray signature profiling,including unsupervised clustering and statistical analysis of differential expression levels,and findings from the published literature.The selected candidate microRNAs were then confirmed using TaqMan real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR) to further narrow down to a three-microRNA diagnostic panel.The three-microRNA diagnostic panel was validated with independent experimental proce-dures and instrumentation of RT-qPCR at an independent venue with a new cohort of cancer patients(n = 11),healthy controls(n = 11),and a group of high risk controls(n = 11).Receiver operating characteristic curve analysis was performed to assess the diagnostic capability of the three-microRNA panel.RESULTS:In the initial high throughput screening,1220 known human microRNAs were screened for differential expression in pancreatic cancer patients versus controls.A subset of 42 microRNAs was then generated based on this data analysis and current published literature.Eight microRNAs were selected from the list of 42 targets for confirmation study,and three-microRNAs,miR-642b,miR-885-5p,and miR-22,were confirmed to show consistent expression between microarray and RT-qPCR.These three microRNAs were then validated and evaluated as a diagnostic panel with a new cohort of patients and controls and found to yield high sensitivity(91%) and specificity(91%) with an area under the curve of 0.97(P < 0.001).Compared to the CA19-9 marker at 73%,the three-microRNA panel has higher sensitivity although CA19-9 has higher specificity of 100%.CONCLUSION:The identified panel of three microRNA biomarkers can potentially be used as a diagnostic tool for early stage pancreatic cancer.

Circulating microRNAs as potential biomarkers for diagnosis of congenital heart defects

BACKGROUND: Micro RNAs are small non-coding RNAs of approximately 22 nucleotides in length, and play important regulatory roles in normal heart development and the pathogenesis of heart diseases. Recently, a few prospective studies have implicated the diagnostic role of micro RNAs in congenital heart defects(CHD).DATA RESOURCES: This review retrieved the research articles in Pub Med focusing on the altered microR NAs in cardiac tissue or serum of patients with CHD versus healthy normal controls, as well as the studies exploring circulating microR NAs as potential biomarkers for(fetal) CHD.RESULTS: Most of the studies of interest were conducted in recent years, implicating that the topic in this review is a newly emerging field and is drawing much attention. Moreover, a number of differentially expressed microR NAs between CHD specimens and normal controls have been reported.CONCLUSION: Circulating micro RNAs may serve as potential biomarkers for diagnosis of CHD in the future, with more efforts paving the road to the aim.

Comprehensive evaluation of microRNA as a biomarker for the diagnosis of hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC) is the most common type of primary liver cancer. Current guidelines for HCC management recommend surveillance of high-risk patients every 6 mo using ultrasonography. Serum biomarkers, like alpha-fetoprotein(AFP), protein induced by vitamin K absence/antagonist-Ⅱ(PIVKA-Ⅱ) and lectin-reactive AFP, show suboptimal performance for detection of HCC, which is crucial for successful resection or treatment. Thus, there is a significant need for new biomarkers to aid early diagnosis of HCC. Studies have shown that the expression level of human microRNAs(miRNAs), a small, non-coding RNA species released into the blood, can serve as an early marker for various diseases, including HCC.AIM To evaluate the diagnostic role of miRNAs in HCC as single markers, signatures or in combination with known protein biomarkers.METHODS Our prospective, multicenter, case-control study recruited 660 participants(354 controls with chronic liver disease and 306 participants with HCC) and employed a strategy of initial screening by two independent methods, real-time quantitative PCR(n = 60) and next-generation sequencing(n = 100), to assess a large number of miRNAs. The results from the next-generation sequencing and real-time quantitative PCR screening approaches were then combined to select 26 miRNAs(including two putative novel miRNAs). Those miRNAs were analyzed for their diagnostic potential as single markers or in combination with other miRNAs or established protein biomarkers AFP and PIVKA-Ⅱ via real-time quantitative PCR in training(n = 200) and validation cohorts(n = 300).RESULTS We identified 26 miRNAs that differentiated chronic liver disease controls from(early) HCC via two independent discovery approaches. Three miRNAs, miR-21-5p(miR-21), miR-320a and miR-186-5p, were selected by both methods. In the training cohort, only miR-21, miR-320d and miR-423could significantly distinguish(Q < 0.05) between the HCC and chronic liver disease control groups. In the multivariate setting, miR-21 with PIVKA-Ⅱ was selected as the best combination,resulting in an area under the curve of 0.87 for diagnosis and area under the curve of 0.74 for early diagnosis of HCC. In the validation cohort, only miR-21 and miR-423 could be confirmed as potential HCC biomarkers. A combination of miRNAs did not perform better than any single miRNA. Improvement of PIVKA-Ⅱ performance through combination with miRNAs could not be confirmed in the validation panel. Two putative miRs, put-miR-6 and put-miR-99, were tested in the training and validation panels, but their expression could only be detected in very few samples and at a low level(cycle threshold between 31.24 and 34.97).CONCLUSION miRNAs alone or as a signature in combination with protein biomarkers AFP and PIVKA-Ⅱ do not improve the diagnostic performance of the protein biomarkers.

Circular RNAs in breast cancer diagnosis,treatment and prognosis

Breast cancer has surpassed lung cancer to become the most common malignancy worldwide.The incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public health.Circular RNAs(circRNAs),a new class of noncoding RNAs(ncRNAs),have been recognized as important oncogenes or suppressors in regulating cancer initiation and progression.In breast cancer,circRNAs have significant roles in tumorigenesis,recurrence and multidrug resistance that are mediated by various mechanisms.Therefore,circRNAs may serve as promising targets of therapeutic strategies for breast cancer management.This study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis,treatment and prognosis evaluation,as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast cancer.Understanding the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.

Activatable fluorescent probes for imaging and diagnosis of rheumatoid arthritis

Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.

MicroRNAs as potential biomarkers in temporal lobe epilepsy and mesial temporal lobe epilepsy

Temporal lobe epilepsy is the most common form of focal epilepsy in adults,accounting for one third of all diagnosed epileptic patients,with seizures originating from or involving mesial temporal structures such as the hippocampus,and many of these patients being refractory to treatment with anti-epileptic drugs.Temporal lobe epilepsy is the most common childhood neurological disorder and,compared with adults,the symptoms are greatly affected by age and brain development.Diagnosis of temporal lobe epilepsy relies on clinical examination,patient history,electroencephalographic recordings,and brain imaging.Misdiagnosis or delay in diagnosis is common.A molecular biomarker that could distinguish epilepsy from healthy subjects and other neurological conditions would allow for an earlier and more accurate diagnosis and appropriate treatment to be initiated.Among possible biomarkers of pathological changes as well as potential therapeutic targets in the epileptic brain are micro RNAs.Most of the recent studies had performed micro RNA profiling in body fluids such as blood plasma and blood serum and brain tissues such as temporal cortex tissue and hippocampal tissue.A large number of micro RNAs were dysregulated when compared to healthy controls and with some overlap between individual studies that could serve as potential biomarkers.For example,in adults with temporal lobe epilepsy,possible biomarkers are miR-199a-3p in blood plasma and miR-142-5p in blood plasma and blood serum.In adults with mesial temporal lobe epilepsy,possible biomarkers are miR-153 in blood plasma and miR-145-3p in blood serum.However,in many of the studies involving patients who receive one or several anti-epileptic drugs,the influence of these on micro RNA expression in body fluids and brain tissues is largely unknown.Further studies are warranted with children with temporal lobe epilepsy and consideration should be given to utilizing mouse or rat and non-human primate models of temporal lobe epilepsy.The animal models could be used to confirm micro RNA findings in human patients and to test the effects of targeting specific micro RNAs on disease progression and behavior.

Blood diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.

Circ_0004592:An auxiliary diagnostic biomarker for gastric cancer

BACKGROUND Gastric cancer(GC)has a high mortality rate,and robust diagnostic biomarkers are currently lacking.However,the clinical relevance of circular RNAs(circRNAs)as GC biomarkers remains largely unexplored.AIM To evaluate the potential of novel circRNA circ_0004592 in the early screening and prognosis of GC.METHODS High-throughput sequencing of circRNAs was performed to screen for potential target molecules.Circ_0004592 expression was examined in GC tissues,cells,and plasma.Plasma samples were collected from healthy subjects’patients,as well as from patients with benign lesions,precancerous lesions,and GC,whereafter the diagnostic accuracy of circ_0004592 was evaluated.The correlation between circ_0004592 levels in plasma and clinicopathological data of patients with GC was further analyzed.RESULTS Circ_0004592 was upregulated in both the tissue and plasma of patients with GC.Further,circ_0004592 expression was higher in patients with precancerous lesions than in healthy controls while being highest in patients with GC.In the same patient,the postoperative plasma level of circ_0004592 was lower than that in the preoperative period.Moreover,circ_0004592 level was significantly correlated with tumor differentiation,tumor depth,and lymph node metastasis.The area under the curve(AUC)of plasma circ_0004592 exhibited high sensitivity and specificity for differentiating patients with GC from healthy donors.Diagnosis based on circ_0004592,carcinoembryonic antigen,and cancer antigen 199 achieved a superior AUC and was highly sensitive.CONCLUSION Plasma circ_0004592 may represent a potential non-invasive auxiliary diagnostic biomarker for patients with GC.

Application of Fusobacterium nucleatum as a biomarker in gastrointestinal malignancies

The morbidity and mortality of gastrointestinal(GI)malignancies are among the highest in the world,posing a serious threat to human health.Because of the insidious onset of the cancer,it is difficult for patients to be diagnosed at an early stage,and it rapidly progresses to an advanced stage,resulting in poor treatment and prognosis.Fusobacterium nucleatum(F.nucleatum)is a gram-negative,sporefree anaerobic bacterium that primarily colonizes the oral cavity and is implicated in the development of colorectal,esophageal,gastric,and pancreatic cancers via various intricate mechanisms.Recent development in novel research suggests that F.nucleatum may function as a biomarker in GI malignancies.Detecting the abundance of F.nucleatum in stool,saliva,and serum samples of patients may aid in the diagnosis,risk assessment,and prognosis monitoring of GI malignancies.This editorial systematically describes the biological roles and mechanisms of F.nucleatum in GI malignancies focusing on the application of F.nucleatum as a biomarker in the diagnosis and prognosis of GI malignancies to promote the clinical translation of F.nucleatum and GI tumors-related research.

From immunology to artificial intelligence: revolutionizing latent tuberculosis infection diagnosis with machine learning

Latent tuberculosis infection(LTBI)has become a major source of active tuberculosis(ATB).Although the tuberculin skin test and interferon-gamma release assay can be used to diagnose LTBI,these methods can only differentiate infected individuals from healthy ones but cannot discriminate between LTBI and ATB.Thus,the diagnosis of LTBI faces many challenges,such as the lack of effective biomarkers from Mycobacterium tuberculosis(MTB)for distinguishing LTBI,the low diagnostic efficacy of biomarkers derived from the human host,and the absence of a gold standard to differentiate between LTBI and ATB.Sputum culture,as the gold standard for diagnosing tuberculosis,is time-consuming and cannot distinguish between ATB and LTBI.In this article,we review the pathogenesis of MTB and the immune mechanisms of the host in LTBI,including the innate and adaptive immune responses,multiple immune evasion mechanisms of MTB,and epigenetic regulation.Based on this knowledge,we summarize the current status and challenges in diagnosing LTBI and present the application of machine learning(ML)in LTBI diagnosis,as well as the advantages and limitations of ML in this context.Finally,we discuss the future development directions of ML applied to LTBI diagnosis.

Advancements and Challenges in Biomarkers for Colorectal Cancer Detection:A Comprehensive Review

This study provides an overview of the current landscape of biomarkers for colorectal cancer(CRC)detection,focusing on genetic,proteomic,circulating microRNA(miRNA),and metabolomic biomarkers.CRC remains a significant global health challenge,ranking among the most prevalent cancers worldwide and being a leading cause of cancer-related deaths.Despite advancements in screening methods such as colonoscopy,sigmoidoscopy,and fecal occult blood tests(FOBT),the asymptomatic nature of early-stage CRC often results in late diagnoses,negatively impacting patient outcomes.Genetic biomarkers like APC,KRAS,TP53,and microsatellite instability(MSI)play critical roles in CRC pathogenesis and progression.These biomarkers,detectable through polymerase chain reaction,next-generation sequencing,and other advanced techniques,guide early detection and personalized treatment decisions.Proteomic biomarkers such as CEA,CA 19-9,and novel signatures offer insights into CRC’s physiological changes and disease status,aiding prognosis and treatment response assessments through enzyme-linked immunosorbent assay and mass spectrometry.Circulating miRNAs,including miR-21 and miR-92a,present promising non-invasive biomarkers that can be detected in blood and stool samples,reflecting CRC presence,progression,and therapeutic response.Metabolomic biomarkers,encompassing amino acids,lipids,and TCA cycle intermediates,provide further insights into CRC-associated metabolic alterations,which are crucial for early detection and treatment monitoring using mass spectrometry and nuclear magnetic resonance.Despite these advancements,challenges such as biomarker validation,standardization,and clinical utility remain.Future research directions include integrating multi-omics approaches and leveraging technologies like liquid biopsies and AI for enhanced biomarker discovery and clinical application.By addressing these challenges and advancing research in biomarker development,CRC screening and management could potentially be revolutionized,improving patient outcomes and reducing the global burden of this disease.

ATM is a Prognostic Biomarker of Survival in Head and Neck Squamous Cell Carcinoma Patients

This review examines the role of ATM expression in head and neck squamous cell carcinoma(HNSCC).Analysis revealed significant overexpression of ATM in HNSCC cells compared to normal control samples,suggesting its involvement in cancer proliferation.ATM expression was notably upregulated across various clinical parameters,including different stages of cancer,racial groups,genders,and age groups,highlighting its role in cancer progression.Validation using the GEPIA2 tool confirmed strong ATM expression throughout all four stages of HNSCC,with the highest levels in stage II and the lowest in stage I.Promoter methylation analysis of ATM showed distinct patterns across different demographics and cancer stages,reinforcing its significance.The study also explored the relationship between ATM expression and patient outcomes using the KM plotter tool,finding that high ATM expression was associated with better overall survival(OS),while low ATM expression correlated with better disease-free survival(DFS).Genetic mutation analysis via cBioPortal identified minimal ATM mutations in HNSCC,including in-frame,splice,truncating,and missense mutations,suggesting their role in ATM dysregulation.The STRING tool was used to construct a protein-protein interaction(PPI)network,revealing that the ATM gene interacts with ten key genes(NBN,ATR,CHEK2,MDC1,MSH2,MSH6,MRE11,TP53,TP53BP1,BRCA1),indicating its involvement in various biological functions.Functional annotation of differentially expressed genes(DEGs)through the DAVID web server revealed their participation in critical biological processes,including double-strand break repair,cellular response to DNA damage,and DNA damage checkpoints.KEGG pathway analysis further linked DEGs to cellular senescence,platinum drug resistance,homologous recombination,p53 signaling,and the cell cycle,underscoring ATM’s multifaceted role in HNSCC.

PTEN as a Novel Diagnostic and Prognostic Biomarker of Head and Neck Squamous Cell Carcinoma

This review article explores phosphatase and tensin homolog(PTEN)’s role in head and neck squamous cell carcinoma(HNSCC)through comprehensive expression and methylation examinations,genetic mutation investigation,and prognostic evaluation.Using the UALCAN informational collection,PTEN expression examination uncovered a critical over-expression in HNSCC cells isolated from normal control samples,proposing its role in HNSCC multiplication.Further,analysis of PTEN expression across various clinical limits has shown critical up-regulation in different cancer development stages,racial groups,gender,and age classes within the context of HNSCC patients,suggesting its major role in cancer duplication.PTEN expression was validated by utilizing the GEPIA2.0 online tool,which showed PTEN expression was particularly significantly expressed in HNSCC cancer improvement when it appeared differently from normal control samples.Accordingly,examining PTEN validation across different phases of cancer advancement showed dysregulation in each of the four phases with the most raised expression in stage I and the least expression in stage IV.Thus,this study investigated the promoter methylation level of PTEN,figuring out a basic relationship between HNSCC samples and normal control samples.Analyzing promoter methylation across various clinical limits uncovered massive variations,with specific methylation patterns seen across malignant growth stages,race groups,gender,and age groups.Overall survival and disease-free survival(OS and DFS)utilizing the KM plotter tool showed a critical relationship between PTEN expression levels in HNSCC patients,showing high PTEN expression exhibited good overall survival when showed up distinctively comparable to low PTEN expression levels.In addition,in disease-free survival(DFS)evaluation HNSCC patients showing low PTEN expression experienced great DFS relative to HNSCC patients with high PTEN expression.Moreover,to validate PTEN expression against survival,the study examined the HNSCC patients into low and high-expression groups of PTEN.In HNSCC,low PTEN expression was connected with great overall survival(OS)when it appeared contrastingly relative to the high PTEN expression.In like manner,the study found that low PTEN expression level was connected with great DFS in HNSCC when it appeared contrastingly related to the high PTEN expression group.Genetic mutation analysis via cBioPortal identifies a minimal proportion of PTEN mutations in HNSCC,predominantly in-frame mutation,missense mutation,splice mutation,truncating mutation,and structural variant,indicating their basal significance in PTEN dysregulation within HNSCC.Further investigation of PTEN molecular components and their exchange inside the HNSCC microenvironment might disclose novel roads for designated treatment and accurate medication approaches in battling this harmful disease.