Biomarker Research最新文献

{"title":"FGL1 and FGL2: emerging regulators of liver health and disease.","authors":"Jiongming Chen, Lei Wu, Yongsheng Li","doi":"10.1186/s40364-024-00601-0","DOIUrl":"10.1186/s40364-024-00601-0","url":null,"abstract":"<p><p>Liver disease is a complex group of diseases with high morbidity and mortality rates, emerging as a major global health concern. Recent studies have highlighted the involvement of fibrinogen-like proteins, specifically fibrinogen-like protein 1 (FGL1) and fibrinogen-like protein 2 (FGL2), in the regulation of various liver diseases. FGL1 plays a crucial role in promoting hepatocyte growth, regulating lipid metabolism, and influencing the tumor microenvironment (TME), contributing significantly to liver repair, non-alcoholic fatty liver disease (NAFLD), and liver cancer. On the other hand, FGL2 is a multifunctional protein known for its role in modulating prothrombin activity and inducing immune tolerance, impacting viral hepatitis, liver fibrosis, hepatocellular carcinoma (HCC), and liver transplantation. Understanding the functions and mechanisms of fibrinogen-like proteins is essential for the development of effective therapeutic approaches for liver diseases. Additionally, FGL1 has demonstrated potential as a disease biomarker in radiation and drug-induced liver injury as well as HCC, while FGL2 shows promise as a biomarker in viral hepatitis and liver transplantation. The expression levels of these molecules offer exciting prospects for disease assessment. This review provides an overview of the structure and roles of FGL1 and FGL2 in different liver conditions, emphasizing the intricate molecular regulatory processes and advancements in targeted therapies. Furthermore, it explores the potential benefits and challenges of targeting FGL1 and FGL2 for liver disease treatment and the prospects of fibrinogen-like proteins as biomarkers for liver disease, offering insights for future research in this field.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11141035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PTK2 is a potential biomarker and therapeutic target for EGFR- or TLRs-induced lung cancer progression via the regulation of the cross-talk between EGFR- and TLRs-mediated signals.","authors":"Ji Young Kim, Ji Hye Shin, Mi-Jeong Kim, Bongkum Choi, Yeeun Kang, Jimin Choi, Seo Hyun Kim, Dohee Kwan, Duk-Hwan Kim, Eunyoung Chun, Ki-Young Lee","doi":"10.1186/s40364-024-00604-x","DOIUrl":"10.1186/s40364-024-00604-x","url":null,"abstract":"<p><p>Protein tyrosine kinase 2 (PTK2), epidermal growth factor receptor (EGFR), and toll-like receptor (TLRs) are amplified in non-small cell lung cancer (NSCLC). However, the functional and clinical associations between them have not been elucidated yet in NSCLC. By using microarray data of non-small cell lung cancer (NSCLC) tumor tissues and matched normal tissues of 42 NSCLC patients, the genetic and clinical associations between PTK2, EGFR, and TLRs were analyzed in NSCLC patients. To verify the functional association, we generated PTK2-knockout (PTK2-KO) lung cancer cells by using CRISPR-Cas9 gene editing method, and performed in vitro cancer progression assay, including 3D tumor spheroid assay, and in vivo xenografted NSG (NOD/SCID/IL-2Rγ^null) mouse assay. Finally, therapeutic effects targeted to PTK2 in lung cancer in response to EGF and TLR agonists were verified by using its inhibitor (Defactinib). In summary, we identified that up-regulated PTK2 might be a reliable marker for EGFR- or TLRs-induced lung cancer progression in NSCLC patients via the regulation of the cross-talk between EGFR- and TLRs-mediated signaling. This study provides a theoretical basis for the therapeutic intervention of PTK2 targeting EGFR- or TLRs-induced lung cancer progression.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11141017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The war between the immune system and the tumor - using immune biomarkers as tracers.","authors":"Kai Yang, Rongrong Lu, Jie Mei, Kai Cao, Tianyu Zeng, Yijia Hua, Xiang Huang, Wei Li, Yongmei Yin","doi":"10.1186/s40364-024-00599-5","DOIUrl":"10.1186/s40364-024-00599-5","url":null,"abstract":"<p><p>Nowadays, immunotherapy is one of the most promising anti-tumor therapeutic strategy. Specifically, immune-related targets can be used to predict the efficacy and side effects of immunotherapy and monitor the tumor immune response. In the past few decades, increasing numbers of novel immune biomarkers have been found to participate in certain links of the tumor immunity to contribute to the formation of immunosuppression and have entered clinical trials. Here, we systematically reviewed the oncogenesis and progression of cancer in the view of anti-tumor immunity, particularly in terms of tumor antigen expression (related to tumor immunogenicity) and tumor innate immunity to complement the cancer-immune cycle. From the perspective of integrated management of chronic cancer, we also appraised emerging factors affecting tumor immunity (including metabolic, microbial, and exercise-related markers). We finally summarized the clinical studies and applications based on immune biomarkers. Overall, immune biomarkers participate in promoting the development of more precise and individualized immunotherapy by predicting, monitoring, and regulating tumor immune response. Therefore, targeting immune biomarkers may lead to the development of innovative clinical applications.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11137916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating long non-coding RNAs detection after heart transplantation and its accuracy in the diagnosis of acute cardiac rejection.","authors":"Lorena Pérez-Carrillo, Isaac Giménez-Escamilla, Irene González-Torrent, Marta Delgado-Arija, Ignacio Sánchez-Lázaro, María García-Manzanares, Luis Martínez-Dolz, Manuel Portolés, Estefanía Tarazón, Esther Roselló-Lletí","doi":"10.1186/s40364-024-00590-0","DOIUrl":"10.1186/s40364-024-00590-0","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) are closely implicated in biological processes and diseases with high inflammatory components. These molecules exhibit significant temporal and tissue specificity. However, the expression and function of lncRNAs have not been studied in patients after heart transplantation. Thus, we aimed to identify circulating lncRNAs in these patients and evaluate their diagnostic capacity as potential biomarkers for the non-invasive detection of acute cellular rejection (ACR). For them, we performed a transcriptomic study based on ncRNA-seq technology to detect lncRNAs in serum samples, matched to routine endomyocardial biopsies, from patients without rejection episode (0R, n = 12) and with mild (1R, n = 16) or moderate-severe (≥ 2R, n = 12) ACR. We identified 11,062 circulating lncRNAs in the serum of patients after heart transplantation. Moreover, 6 lncRNAs showed statistically significant expression when the different ACR grades were compared. Among them, AC008105.3, AC006525.1, AC011455.8, AL359220.1, and AC025279.1 had relevant diagnostic capacity for detection of ≥ 2R (AUC of 0.850 to 1.000) and 1R (AUC of 0.750 to 0.854) grades, along with high specificity and positive predictive values (≥ 83%). In addition, AL359220.1 and AC025279.1 were independent predictors for the presence of moderate-severe ACR (odds ratio = 31.132, p < 0.01 and C statistic = 0.939, p < 0.0001; odds ratio = 18.693, p < 0.05 and C statistic = 0.902, p < 0.001; respectively). In conclusion, we describe, for the first time, circulating lncRNAs after heart transplantation as potential candidates for non-invasive detection of ACR. AL359220.1 and AC025279.1 showed excellent diagnostic capability correlating with the severity episode and were strong independent predictors of rejection.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140913106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD19-immunoPET for noninvasive visualization of CD19 expression in B-cell lymphoma patients.","authors":"Dominik Sonanini, Johannes Schwenck, Simone Blaess, Julia Schmitt, Andreas Maurer, Walter Ehrlichmann, Malte Ritter, Julia Skokowa, Manfred Kneilling, Gundram Jung, Falko Fend, Simon Krost, Christian M Seitz, Peter Lang, Gerald Reischl, Rupert Handgretinger, Christian la Fougère, Bernd J Pichler","doi":"10.1186/s40364-024-00595-9","DOIUrl":"10.1186/s40364-024-00595-9","url":null,"abstract":"<p><p>Cell- and antibody-based CD19-directed therapies have demonstrated great potential for treating B-cell non-Hodgkin lymphoma (B-NHL). However, all these approaches suffer from limited response rates and considerable toxicity. Until now, therapy decisions have been routinely based on histopathological CD19 staining of a single lesion at initial diagnosis or relapse, disregarding heterogeneity and temporal alterations in antigen expression. To visualize in vivo CD19 expression noninvasively, we radiolabeled anti-human CD19 monoclonal antibodies with copper-64 (⁶⁴Cu-αCD19) for positron emission tomography (CD19-immunoPET). ⁶⁴Cu-αCD19 specifically bound to subcutaneous Daudi xenograft mouse models in vivo. Importantly, ⁶⁴Cu-αCD19 did not affect the anti-lymphoma cytotoxicity of CD19 CAR-T cells in vitro. Following our preclinical validation, ⁶⁴Cu-αCD19 was injected into four patients with follicular lymphoma, diffuse large B-cell lymphoma or mantle zone lymphoma. We observed varying ⁶⁴Cu-αCD19 PET uptake patterns at different lymphoma sites, both within and among patients, correlating with ex vivo immunohistochemical CD19 expression. Moreover, one patient exhibited enhanced uptake in the spleen compared to that in patients with prior B-cell-depleting therapy, indicating that ⁶⁴Cu-αCD19 is applicable for identifying B-cell-rich organs. In conclusion, we demonstrated the specific targeting and visualization of CD19⁺ B-NHL in mice and humans by CD19-immunoPET. The intra- and interindividual heterogeneous ⁶⁴Cu-αCD19 uptake patterns of lymphoma lesions indicate variability in CD19 expression, suggesting the potential of CD19-immunoPET as a novel tool to guide CD19-directed therapies.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140913039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering metabolic heterogeneity in retinoblastoma unravels the role of monocarboxylate transporter 1 in tumor progression.","authors":"Junjie Tang, Yaoming Liu, Yinghao Wang, Zhihui Zhang, Jiahe Nie, Xinyue Wang, Siming Ai, Jinmiao Li, Yang Gao, Cheng Li, Chao Cheng, Shicai Su, Shuxia Chen, Ping Zhang, Rong Lu","doi":"10.1186/s40364-024-00596-8","DOIUrl":"10.1186/s40364-024-00596-8","url":null,"abstract":"<p><strong>Background: </strong>Tumors exhibit metabolic heterogeneity, influencing cancer progression. However, understanding metabolic diversity in retinoblastoma (RB), the primary intraocular malignancy in children, remains limited.</p><p><strong>Methods: </strong>The metabolic landscape of RB was constructed based on single-cell transcriptomic sequencing from 11 RB and 5 retina samples. Various analyses were conducted, including assessing overall metabolic activity, metabolic heterogeneity, and the correlation between hypoxia and metabolic pathways. Additionally, the expression pattern of the monocarboxylate transporter (MCT) family in different cell clusters was examined. Validation assays of MCT1 expression and function in RB cell lines were performed. The therapeutic potential of targeting MCT1 was evaluated using an orthotopic xenograft model. A cohort of 47 RB patients was analyzed to evaluate the relationship between MCT1 expression and tumor invasion.</p><p><strong>Results: </strong>Distinct metabolic patterns in RB cells, notably increased glycolysis, were identified. This metabolic heterogeneity correlated closely with hypoxia. MCT1 emerged as the primary monocarboxylate transporter in RB cells. Disrupting MCT1 altered cell viability and energy metabolism. In vivo studies using the MCT1 inhibitor AZD3965 effectively suppressed RB tumor growth. Additionally, a correlation between MCT1 expression and optic nerve invasion in RB samples suggested prognostic implications.</p><p><strong>Conclusions: </strong>This study enhances our understanding of RB metabolic characteristics at the single-cell level, highlighting the significance of MCT1 in RB pathogenesis. Targeting MCT1 holds promise as a therapeutic strategy for combating RB, with potential prognostic implications.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11088057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140905185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antileukemic potential of methylated indolequinone MAC681 through immunogenic necroptosis and PARP1 degradation","authors":"Barbora Orlikova-Boyer, Anne Lorant, Sruthi Reddy Gajulapalli, Claudia Cerella, Michael Schnekenburger, Jin-Young Lee, Ji Yeon Paik, Yejin Lee, David Siegel, David Ross, Byung Woo Han, Thi Kim Yen Nguyen, Christo Christov, Hyoung Jin Kang, Mario Dicato, Marc Diederich","doi":"10.1186/s40364-024-00594-w","DOIUrl":"https://doi.org/10.1186/s40364-024-00594-w","url":null,"abstract":"Despite advancements in chronic myeloid leukemia (CML) therapy with tyrosine kinase inhibitors (TKIs), resistance and intolerance remain significant challenges. Leukemia stem cells (LSCs) and TKI-resistant cells rely on altered mitochondrial metabolism and oxidative phosphorylation. Targeting rewired energy metabolism and inducing non-apoptotic cell death, along with the release of damage-associated molecular patterns (DAMPs), can enhance therapeutic strategies and immunogenic therapies against CML and prevent the emergence of TKI-resistant cells and LSC persistence. Transcriptomic analysis was conducted using datasets of CML patients' stem cells and healthy cells. DNA damage was evaluated by fluorescent microscopy and flow cytometry. Cell death was assessed by trypan blue exclusion test, fluorescent microscopy, flow cytometry, colony formation assay, and in vivo Zebrafish xenografts. Energy metabolism was determined by measuring NAD+ and NADH levels, ATP production rate by Seahorse analyzer, and intracellular ATP content. Mitochondrial fitness was estimated by measurements of mitochondrial membrane potential, ROS, and calcium accumulation by flow cytometry, and morphology was visualized by TEM. Bioinformatic analysis, real-time qPCR, western blotting, chemical reaction prediction, and molecular docking were utilized to identify the drug target. The immunogenic potential was assessed by high mobility group box (HMGB)1 ELISA assay, luciferase-based extracellular ATP assay, ectopic calreticulin expression by flow cytometry, and validated by phagocytosis assay, and in vivo vaccination assay using syngeneic C57BL/6 mice. Transcriptomic analysis identified metabolic alterations and DNA repair deficiency signatures in CML patients. CML patients exhibited enrichment in immune system, DNA repair, and metabolic pathways. The gene signature associated with BRCA mutated tumors was enriched in CML datasets, suggesting a deficiency in double-strand break repair pathways. Additionally, poly(ADP-ribose) polymerase (PARP)1 was significantly upregulated in CML patients’ stem cells compared to healthy counterparts. Consistent with the CML patient DNA repair signature, treatment with the methylated indolequinone MAC681 induced DNA damage, mitochondrial dysfunction, calcium homeostasis disruption, metabolic catastrophe, and necroptotic-like cell death. In parallel, MAC681 led to PARP1 degradation that was prevented by 3-aminobenzamide. MAC681-treated myeloid leukemia cells released DAMPs and demonstrated the potential to generate an immunogenic vaccine in C57BL/6 mice. MAC681 and asciminib exhibited synergistic effects in killing both imatinib-sensitive and -resistant CML, opening new therapeutic opportunities. Overall, increasing the tumor mutational burden by PARP1 degradation and mitochondrial deregulation makes CML suitable for immunotherapy.","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140840179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenomic landscape and pharmacogenomic implications for HLA region in a Taiwan Han Chinese population","authors":"Wan-Hsuan Chou, Lu-Chun Chen, Henry Sung-Ching Wong, Ching-Hsuan Chao, Hou-Wei Chu, Wei-Chiao Chang","doi":"10.1186/s40364-024-00591-z","DOIUrl":"https://doi.org/10.1186/s40364-024-00591-z","url":null,"abstract":"The human leukocyte antigen (HLA) genes, exhibiting significant genetic diversity, are associated with susceptibility to various clinical diseases and diverse in drug responses. High costs of HLA sequencing and the population-specific architecture of this genetic region necessitate the establishment of a population-specific HLA imputation reference panel. Moreover, there is a lack of understanding about the genetic and phenotypic landscape of HLA variations within the Taiwanese population. We created models for a Taiwanese-specific HLA imputation reference panel. These models were trained with the array genotype data and HLA sequencing data from 845 Taiwanese subjects. HLA imputation was applied for 59,448 Taiwanese subjects to characterize the HLA allele and haplotype frequencies. Additionally, a phenome-wide association study (PheWAS) was conducted to identify the phenotypes associated with HLA variations. The association of the biallelic HLA variants with the binary and quantitative traits were evaluated with additive logistic and linear regression models, respectively. Furthermore, an omnibus test with likelihood-ratio test was applied for each HLA amino acid position in the multiallelic HLA amino acid polymorphisms to compare the difference between a fitted model and a null model following a χ2 distribution of n-1 degree of freedom at a position with n residues. Finally, we estimated the prevalence of adverse drug reactions (ADR)-related HLA alleles in the Taiwanese population. In this study, the reference panel models displayed remarkable accuracy, with averages of 99.3%, 98.9%, and 99.1% for 2-, 4-, 6-digit alleles of the eight classical HLA genes, respectively. For PheWAS, a total of 18,136 significant associations with HLA variants across 26 phenotypes are identified (p < 5×10-8), highlighting the pleiotropy feature of the HLA region. Among the independent signals, 15 are novel, including the association of HLA-B pos 138 variation with ankylosing spondylitis (AS), and rs9266290 and rs9266292 with allergy. Through an analysis spanning the entire HLA region, we identified clusters of phenotype correlations. Finally, the carriers of pharmacogenomic related HLA alleles, including HLA-C*01:02 (35.86%), HLA-B*58:01 (20.9%), and HLA-B*15:02 (8.38%), were characterized in the Taiwanese general population. We successfully delivered the HLA imputation for 59,448 Taiwanese subjects and characterized the genetic and phenotypic landscapes of the HLA variations. In addition, we quantified the estimated prevalence of the ADR-related HLA alleles in the Taiwanese population. The developed HLA imputation reference panel could be used for estimation of population HLA allele frequencies, which can facilitate further studies in the role of HLA variants in a wider range of phenotypes in the population.","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140840456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disulfidptosis decoded: a journey through cell death mysteries, regulatory networks, disease paradigms and future directions","authors":"Jinyu Chen, Boyuan Ma, Yubiao Yang, Bitao Wang, Jian Hao, Xianhu Zhou","doi":"10.1186/s40364-024-00593-x","DOIUrl":"https://doi.org/10.1186/s40364-024-00593-x","url":null,"abstract":"Cell death is an important part of the life cycle, serving as a foundation for both the orderly development and the maintenance of physiological equilibrium within organisms. This process is fundamental, as it eliminates senescent, impaired, or aberrant cells while also promoting tissue regeneration and immunological responses. A novel paradigm of programmed cell death, known as disulfidptosis, has recently emerged in the scientific circle. Disulfidptosis is defined as the accumulation of cystine by cancer cells with high expression of the solute carrier family 7 member 11 (SLC7A11) during glucose starvation. This accumulation causes extensive disulfide linkages between F-actins, resulting in their contraction and subsequent detachment from the cellular membrane, triggering cellular death. The RAC1-WRC axis is involved in this phenomenon. Disulfidptosis sparked growing interest due to its potential applications in a variety of pathologies, particularly oncology, neurodegenerative disorders, and metabolic anomalies. Nonetheless, the complexities of its regulatory pathways remain elusive, and its precise molecular targets have yet to be definitively identified. This manuscript aims to meticulously dissect the historical evolution, molecular underpinnings, regulatory frameworks, and potential implications of disulfidptosis in various disease contexts, illuminating its promise as a groundbreaking therapeutic pathway and target.","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140840187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma ALS and Gal-3BP differentiate early from advanced liver fibrosis in MASLD patients","authors":"David Pérez Compte, Lucas Etourneau, Anne-Marie Hesse, Alexandra Kraut, Justine Barthelon, Nathalie Sturm, Hélène Borges, Salomé Biennier, Marie Courçon, Marc de Saint Loup, Victoria Mignot, Charlotte Costentin, Thomas Burger, Yohann Couté, Christophe Bruley, Thomas Decaens, Michel Jaquinod, Jérôme Boursier, Virginie Brun","doi":"10.1186/s40364-024-00583-z","DOIUrl":"https://doi.org/10.1186/s40364-024-00583-z","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD) is estimated to affect 30% of the world’s population, and its prevalence is increasing in line with obesity. Liver fibrosis is closely related to mortality, making it the most important clinical parameter for MASLD. It is currently assessed by liver biopsy – an invasive procedure that has some limitations. There is thus an urgent need for a reliable non-invasive means to diagnose earlier MASLD stages. A discovery study was performed on 158 plasma samples from histologically-characterised MASLD patients using mass spectrometry (MS)-based quantitative proteomics. Differentially abundant proteins were selected for verification by ELISA in the same cohort. They were subsequently validated in an independent MASLD cohort (n = 200). From the 72 proteins differentially abundant between patients with early (F0-2) and advanced fibrosis (F3-4), we selected Insulin-like growth factor-binding protein complex acid labile subunit (ALS) and Galectin-3-binding protein (Gal-3BP) for further study. In our validation cohort, AUROCs with 95% CIs of 0.744 [0.673 – 0.816] and 0.735 [0.661 – 0.81] were obtained for ALS and Gal-3BP, respectively. Combining ALS and Gal-3BP improved the assessment of advanced liver fibrosis, giving an AUROC of 0.796 [0.731. 0.862]. The {ALS; Gal-3BP} model surpassed classic fibrosis panels in predicting advanced liver fibrosis. Further investigations with complementary cohorts will be needed to confirm the usefulness of ALS and Gal-3BP individually and in combination with other biomarkers for diagnosis of liver fibrosis. With the availability of ELISA assays, these findings could be rapidly clinically translated, providing direct benefits for patients. ","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140808833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}