Siddig Ibrahim Abdelwahab , Manal Mohamed Elhassan Taha , Khaled A. Sahli , Hatem Ahmed Salem Alqhtani , Abdullah Farasani , Nizar A. Khamjan , Humaid Al-shamsi , Jobran M. Moshi , Saeed Alshahrani , Ahmad Assiri , Marwa Qadri , Syam Mohan
{"title":"Graphene-based biosensors for PSA","authors":"Siddig Ibrahim Abdelwahab , Manal Mohamed Elhassan Taha , Khaled A. Sahli , Hatem Ahmed Salem Alqhtani , Abdullah Farasani , Nizar A. Khamjan , Humaid Al-shamsi , Jobran M. Moshi , Saeed Alshahrani , Ahmad Assiri , Marwa Qadri , Syam Mohan","doi":"10.1016/j.cca.2025.120406","DOIUrl":"10.1016/j.cca.2025.120406","url":null,"abstract":"<div><div>Prostate cancer is a leading cause of cancer-related mortality among men worldwide. Early and accurate detection is critical for effective treatment and improved patient outcomes. Although prostate-specific antigen (PSA) remains the primary biomarker for screening, conventional assays often lack the sensitivity and specificity required for reliable diagnostics. In this review, we evaluate the emerging role of graphene-based biosensors in PSA detection and their potential to transform prostate cancer diagnostics. Graphene’s exceptional properties including a high surface-to-volume ratio and outstanding electrical conductivity make it an ideal platform for biosensing applications. We classify graphene-based sensors into three categories: electrochemical sensors, field-effect transistors (FETs), and fluorescence-based sensors, and discuss the mechanisms by which each detects PSA. Strategies for integrating graphene with other nanomaterials to enhance analytical performance are highlighted. We also assess the clinical feasibility of these platforms, emphasizing their rapid response times, high accuracy, and minimally invasive operation. Finally, we discuss current challenges and future perspectives for translating graphene-based PSA biosensors from laboratory research to routine clinical practice.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"576 ","pages":"Article 120406"},"PeriodicalIF":3.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Min Pan , Xinling Cheng , Huike Chen , Yuxian Feng , Zeyu Ma , Qinyu Ge , Jing Tu
{"title":"Cell-free DNA methylation and its potential as a biomarker in liquid biopsy: A systematic review","authors":"Min Pan , Xinling Cheng , Huike Chen , Yuxian Feng , Zeyu Ma , Qinyu Ge , Jing Tu","doi":"10.1016/j.cca.2025.120403","DOIUrl":"10.1016/j.cca.2025.120403","url":null,"abstract":"<div><div>DNA methylation is a critical epigenetic modification that regulates gene expression. Changes in cell-free DNA (cfDNA) methylation typically precede the clinical manifestations of diseases. Trace amounts in body fluid samples, fragmented feature, and high background noise are the challenges to be addressed before implementation of cfDNA methylation assay in clinical application. With advances in genomic analysis and methylation detection technologies, analysis of cfDNA methylation has emerged as a promising biomarker for early diagnosis, prognostic prediction, and tracing tissue origin. The tissue-specific methylation patterns of cfDNA further facilitate the determination of its tissue of origin, making cfDNA methylation invaluable in liquid biopsies. This review highlights the advanced technologies to analyze methylated cfDNA, summarizes the recent progress of cfDNA methylation assays in clinical applications, and underscores the value of the integration of cfDNA methylation with multi-omics analysis in future research.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"576 ","pages":"Article 120403"},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Surya Nath Pandey , Ehssan Moglad , Gaurav Gupta , H. Malathi , Laxmidhar Maharana , Sami I. Alzarea , Imran Kazmi , Abida Khan
{"title":"Creatine kinase in prostate cancer: A biosensor-driven diagnostic paradigm","authors":"Surya Nath Pandey , Ehssan Moglad , Gaurav Gupta , H. Malathi , Laxmidhar Maharana , Sami I. Alzarea , Imran Kazmi , Abida Khan","doi":"10.1016/j.cca.2025.120402","DOIUrl":"10.1016/j.cca.2025.120402","url":null,"abstract":"<div><h3>Background</h3><div>Prostate cancer (PC) remains a leading cause of cancer-related morbidity in men worldwide. Emerging evidence suggests that the brain-type creatine kinase isoenzyme (CK-BB) is overexpressed in PC tissue and correlates with tumor progression. However, conventional assays for CK-BB lack the sensitivity and rapid turnaround required for routine clinical use.</div></div><div><h3>Methods/Technology</h3><div>We reviewed recent advances in CK-BB-targeted biosensors across three platform categories. First, electrochemical sensors enhanced with nanomaterials such as graphene and gold nanoparticles have produced amplified current or impedance signals for ultra-sensitive CK-BB detection. Second, optical sensors, including fluorescence and surface plasmon resonance systems that incorporate quantum dots and plasmonic nanoparticles, offer label-free real-time monitoring. Third, emerging formats, from paper-based strips to wearable devices and microfluidic lab-on-a-chip assays, promise point-of-care applicability. Integration of artificial intelligence (AI) with microfluidics was also evaluated for automated, real-time CK-BB profiling.</div><div>Key findings</div><div>Nanomaterial-modified electrodes achieved detection limits for CK-BB in the low picogram-per-milliliter range, outperforming standard immunoassays in both assay speed (minutes versus hours) and analytical sensitivity. Clinical discrimination between malignant and benign prostatic conditions exceeded 85 percent accuracy in small patient cohorts, demonstrating the potential diagnostic value of CK-BB biosensing. Nevertheless, device reproducibility and matrix interference remain significant challenges, and only a few platforms have progressed beyond proof-of-concept to larger-scale clinical validation. Preliminary applications of machine-learning algorithms to sensor output show promise in reducing false positives and automating interpretation.</div></div><div><h3>Conclusion</h3><div>CK-BB-targeted biosensors hold considerable promise as an adjunct to prostate-specific antigen testing by enabling faster, more sensitive detection of metabolic changes associated with prostate cancer. To facilitate translation into routine clinical practice, future efforts must focus on standardizing calibration protocols, validating performance in diverse patient populations, and addressing manufacturing and regulatory hurdles. Moreover, coupling CK-BB detection with multiplexed biomarker panels and AI-driven analysis may further enhance diagnostic precision and support truly personalized management of prostate cancer.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"576 ","pages":"Article 120402"},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saba Hadi , Seyed Hossein Khoshraftar , Amir Hossein Kiani Darabi , Anahita Soleimani , Hamid Reza Nejabati
{"title":"Extracellular fluid miRNAs in PCOS","authors":"Saba Hadi , Seyed Hossein Khoshraftar , Amir Hossein Kiani Darabi , Anahita Soleimani , Hamid Reza Nejabati","doi":"10.1016/j.cca.2025.120404","DOIUrl":"10.1016/j.cca.2025.120404","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS) is a prevalent endocrine condition that impacts both reproductive and metabolic functioning. Despite thorough research, the exact causes of PCOS remain unclear. Recent studies indicate that microRNAs (miRNAs), which are small non-coding RNAs that regulate gene expression, could be crucial for comprehending PCOS. This review article investigates the variations in extracellular fluids miRNAs expression in individuals diagnosed with PCOS and assesses their viability as diagnostic biomarkers, and determines their involvement in the mechanisms underlying the disease. The related reports show that miRNA expression profiles demonstrate notable differences between PCOS patients and healthy subjects. Several miRNAs exhibit dysregulation in essential biological processes such as follicular development, steroidogenesis, insulin signaling, and metabolic pathways. These results imply that miRNAs could lead to hormonal imbalances and metabolic problems linked to PCOS. The variations in miRNA expression noted in patients with PCOS underscore their possible role as biomarkers for the early detection and characterization of the condition. Continued investigation into miRNA-based diagnostic and therapeutic strategies may enhance our comprehension of PCOS. and facilitate the advancement of more precise therapeutic alternatives.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"576 ","pages":"Article 120404"},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Faizah Ahmad , Shahrul Aiman Soelar , Mowaffaq Adam Ahmed Adam , Muhammad Radzi Abu Hassan , Muhammad Amir Yunus
{"title":"MicroRNA isolation from urine: comparison of total RNA isolation (TRI) reagent and silica membrane-based extraction methods","authors":"Faizah Ahmad , Shahrul Aiman Soelar , Mowaffaq Adam Ahmed Adam , Muhammad Radzi Abu Hassan , Muhammad Amir Yunus","doi":"10.1016/j.cca.2025.120396","DOIUrl":"10.1016/j.cca.2025.120396","url":null,"abstract":"<div><h3>Background</h3><div>microRNA (miRNA) extraction from urine samples is challenging, especially for sensitive downstream analyses such as quantitative reverse transcription polymerase chain reaction (RT-qPCR). While commercial kits are available, their high cost can be prohibitive for repetitive experimental studies. In this context, this study aimed to compare the RNA yield and purity scores of conventional Total RNA Isolation (TRI) reagent-based to silica membrane-based extraction method.</div></div><div><h3>Methods</h3><div>miRNA was extracted from urine samples using three methods: 1) Silica membrane-based (Method 1); 2) TRI reagent-based (Method 2); and 3) Improvised TRI reagent-based (Method 3). RNA yield and purity score (A260/280 and A260/230) were analysed using one-way repeated measures ANOVA. The relative expression of hsa-miR-21-5p normalized to RNU6B was assessed by RT-qPCR for extracts from Method 1 and 2 to compare the effects of silica membrane-based and TRI reagent-based.</div></div><div><h3>Results</h3><div>Total RNA yield (<em>p</em>-value = 0.005) and A260/230 (<em>p</em>-value < 0.001) differed significantly between all methods except for the A260/280 (<em>p</em>-value = 0.177). Specifically, higher RNA yield and <em>A</em><sub>260/230</sub> from Method 3 were noted compared to Method 1 (<em>p</em>-value = 0.007 and 0.010) and Method 2 (<em>p</em>-value = 0.046 and 0.009), with A260/230 remaining outside the acceptable range. The total RNA yield, A260/280 and A260/230, is not significantly different between Methods 1 and 2 (<em>p</em>-value = 0.291, 0.566, and 1.000).</div></div><div><h3>Conclusion</h3><div>While the purity could be improved, TRI reagent method shows promise as an alternative for high-yield RNA extraction. It is particularly useful for repetitive downstream experiments in research and clinical applications.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"576 ","pages":"Article 120396"},"PeriodicalIF":3.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Emerging blood biomarkers in Alzheimer’s disease: a proteomic perspective","authors":"Neeraj Patel , Neetu Agrawal , Rakhi Mishra , M.M. Rekha , Priya Priyadarshini Nayak , Mandeep Kaur , Anil Khachi , Kavita Goyal , A Rekha , Mohit Rana , Ghala Alnuaimi , Rashi Kulshrestha","doi":"10.1016/j.cca.2025.120397","DOIUrl":"10.1016/j.cca.2025.120397","url":null,"abstract":"<div><div>Early detection of Alzheimer’s disease (AD) remains a formidable clinical challenge, but emerging blood-based assays show promise for identifying at-risk individuals long before cognitive symptoms arise. This is the first comprehensive synthesis comparing mass-spectrometry and immunoassay platforms across multiple blood-based AD biomarkers and the first to integrate these findings into a unified roadmap for clinical implementation. In this review, we compare high-throughput mass spectrometry and ultrasensitive immunoassays for quantifying circulating amyloid-β isoforms, phosphorylated tau species (p-tau181, p-tau217), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), YKL-40 and selected inflammatory markers. Individual biomarkers demonstrate diagnostic accuracies (AUC) up to 0.90, and integrating these protein signatures with APOE ε4 genotype, brief cognitive assessments and neuroimaging via machine-learning models boosts discrimination of preclinical AD from normal aging to over 80% accuracy. We trace the path from initial discovery through analytical validation to clinical implementation, emphasizing critical hurdles such as variability in sample collection, limited cohort diversity and regulatory requirements. Future work must standardize preanalytical protocols, extend validation across populations, refine ultrasensitive detection techniques, and combine proteomic data with genomics and other “omics” layers to move toward routine blood-based screening. These coordinated efforts provide a clear roadmap for transforming early AD diagnosis and enabling timely, personalized interventions.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"576 ","pages":"Article 120397"},"PeriodicalIF":3.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeremiah Sik Bit Tseung , Hok Fung Tong , Tammy Tsz Yan Tong , Yuen Fun Mak , Antony Chun Cheung Fu , Victor Hin Fai Hung , Chor Kwan Ching
{"title":"Co-occurrence of congenital isolated FSH deficiency and androgen-secreting steroid cell tumour in a Chinese female – Intermittent menses in a patient with primary amenorrhoea","authors":"Jeremiah Sik Bit Tseung , Hok Fung Tong , Tammy Tsz Yan Tong , Yuen Fun Mak , Antony Chun Cheung Fu , Victor Hin Fai Hung , Chor Kwan Ching","doi":"10.1016/j.cca.2025.120398","DOIUrl":"10.1016/j.cca.2025.120398","url":null,"abstract":"<div><h3>Background</h3><div>Congenital isolated FSH deficiency is a rare autosomal recessive disorder characterized by primary amenorrhoea, absent or partial breast development, infertility, undetectable serum FSH, and pathogenic variant detected in <em>FSHB</em> gene. Ovarian steroid cell tumour is another rare disease entity that can present in the young, with features of androgenic, estrogenic, or cortisol excess. To date, there have been no reports of the two disease entities occurring in a single patient.</div></div><div><h3>Case report</h3><div>A Chinese female presented with primary amenorrhoea and undetectable serum FSH at the age of 16. She developed spontaneous menses intriguingly at the age of 19, with elevated serum testosterone, leading to subsequent diagnosis of right ovarian steroid cell tumour, not otherwise specified (NOS). After surgical resection, the patient redeveloped amenorrhoea, along with normalized testosterone and undetectable estradiol. Sequencing of <em>FSHB</em> gene revealed homozygosity of a novel variant c.366C > A p.(Cys122*), which is predicted to disrupt FSH heterodimer formation.</div></div><div><h3>Literature review and discussion</h3><div>Literature and case reports on congenital isolated FSH deficiency and steroid cell tumours published in English language were reviewed. The common involvement of gonadotropins and sex steroids by the two pathologies raises the suspicion of possible disease linkage.</div></div><div><h3>Conclusion</h3><div>We herein report the first case of steroid cell tumour identified in a Chinese female with isolated FSH deficiency. The unique presentation of primary amenorrhoea, spontaneous menses, and secondary amenorrhoea post-surgery highlights the role of peripheral aromatization in FSH deficiency. Co-occurrence of the two rare disease entities may help uncover the role of FSH, inhibin, and LH in ovarian tumorigenesis.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"576 ","pages":"Article 120398"},"PeriodicalIF":3.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xudong Jin , Jinhua Rong , Shen Peng , You Xiao , Ruting Wang , Yixuan Gu , Wenhao Ji , Xiancong Huang , Weimin Mao
{"title":"Integrated metabolomics and lipidomics reveal plasma markers of non-small cell lung cancer with brain metastasis","authors":"Xudong Jin , Jinhua Rong , Shen Peng , You Xiao , Ruting Wang , Yixuan Gu , Wenhao Ji , Xiancong Huang , Weimin Mao","doi":"10.1016/j.cca.2025.120399","DOIUrl":"10.1016/j.cca.2025.120399","url":null,"abstract":"<div><div>Brain metastasis (BM) is a fatal complication of non-small cell lung cancer (NSCLC). The lack of non-invasion methods for early diagnosis and risk stratification is the major cause for the poor prognosis of NSCLC with BM. The metabolic state of BM has a significant change characterized with high reactive oxygen species accumulation and the subsequent antioxidant metabolic response. We sought to screen plasma markers based on metabolomics and lipidomics for the early diagnosis and prognostic evaluation of NSCLC patients with BM. Plasma samples collected from 48 NSCLC patients with BM and 49 gender- and age- matched primary lung cancer (PLC) patients were randomly divided into train set and test set, then analyzations of metabolomics and lipidomics were performed using liquid chromatography-tandem mass spectrometry (LC-MS). Differential metabolites and lipids were discovered from the train set. A diagnostic biomarker panel was constructed using logistic regression. The test set were utilized to validate the accuracy of the diagnostic model. Furthermore, a risk score was established to stratify risk for NSCLC patients. There were 34 differential metabolites and 35 differential lipids annotated in the train set. The diagnostic biomarker panel consisting of homocysteine, ascorbic acid, LPC (22:0) and LPC (20:0) is able to discriminate BM from PLC with an excellent performance. The risk score based on protocatechuic acid and LPC (20:0) could efficiently stratify risk for NSCLC patients with BM. Our study reports plasma biomarkers and predictive models for the early diagnosis and prognostic evaluation of NSCLC patients with BM.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"576 ","pages":"Article 120399"},"PeriodicalIF":3.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Is (self-collected) capillary blood for CEA testing compromised by potential contamination of CEA originating from sweat?","authors":"Huub H. van Rossum","doi":"10.1016/j.cca.2025.120400","DOIUrl":"10.1016/j.cca.2025.120400","url":null,"abstract":"","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"576 ","pages":"Article 120400"},"PeriodicalIF":3.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Surya Nath Pandey , M. Arockia Babu , Haider Ali , Malathi H , Laxmidhar Maharana , Kavita Goyal , Mohit Rana , Mohd Imran
{"title":"MUC1 as a diagnostic biomarker and siRNA-based therapeutic target in breast cancer: A clinical chemistry perspective","authors":"Surya Nath Pandey , M. Arockia Babu , Haider Ali , Malathi H , Laxmidhar Maharana , Kavita Goyal , Mohit Rana , Mohd Imran","doi":"10.1016/j.cca.2025.120387","DOIUrl":"10.1016/j.cca.2025.120387","url":null,"abstract":"<div><div>Breast cancer remains the leading cause of cancer mortality in women, and early detection coupled with real-time monitoring of tumor burden are clinical imperatives; yet existing imaging-based screening (e.g., mammography, ultrasound) suffers from sensitivities as low as 60–80% and even lower in dense breasts plus substantial false-positive rates, underscoring the critical need for molecular assays with higher accuracy. Current clinical assays for circulating MUC1 (CA15-3) achieve high specificity but exhibit limited sensitivity in early‐stage disease, underscoring a critical unmet need for more sensitive, multiplexed biomarkers to enable timely intervention. Mass spectrometry-based glycoproteomic workflows offer multiplexed quantification of tumour-associated MUC1 glycoforms, substantially improving analytical specificity and dynamic range. Complementary liquid-biopsy platforms that detect anti-MUC1 autoantibodies further extend lead time for recurrence detection. Concurrently, small interfering RNA (siRNA) therapies targeting MUC1 delivered via ionizable lipid nanoparticles demonstrate efficient tumor accumulation, robust mRNA knockdown, and favourable safety in phase<!--> <!-->I solid tumor trials. In this review, we critically assess the analytical performance and standardization challenges of current MUC1 assays, evaluate emerging mass spectrometry and immunoarray techniques, and examine chemical and nanocarrier strategies that surmount biological barriers to siRNA delivery. We propose a co-development framework for harmonized companion diagnostics and MUC1-directed RNAi therapeutics under unified regulatory pathways, paving the way for precision, biomarker-driven interventions in breast cancer care.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"576 ","pages":"Article 120387"},"PeriodicalIF":3.2,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}