{"title":"Predictive value of TGF-β1 and SMAD-7 expression at diagnosis for treatment response in low-risk myelodysplastic syndrome.","authors":"Bedrettin Orhan, Hülya Öztürk Nazlıoğlu, Oğuzhan Dik, Büşra Gürbüz, Vildan Özkocaman, Tuba Ersal, İbrahim Ethem Pınar, Cumali Yalçın, Sinem Çubukçu, Tuba Güllü Koca, Fazıl Çağrı Hunutlu, Şeyma Yavuz, Rıdvan Ali, Fahir Özkalemkaş","doi":"10.17305/bb.2025.11564","DOIUrl":"10.17305/bb.2025.11564","url":null,"abstract":"<p><p>Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disease. Supportive treatments, such as erythropoiesis-stimulating agents (ESAs), are commonly used in patients with low-risk MDS. This study aimed to retrospectively assess the impact of bone marrow Mothers against decapentaplegic homolog 7 (SMAD-7) and transforming growth factor beta 1 (TGF-β1) protein expression on prognosis and response to ESA treatment in patients with low-risk MDS. We retrospectively analyzed patients diagnosed with low-risk MDS at the adult hematology department of Bursa Uludağ University Hospital. A total of 56 patients classified as low or very low risk were included in the study. Immunohistochemical analysis of bone marrow specimens at diagnosis showed that only five patients (9.8%) exhibited low SMAD-7 staining, while 51 patients (90.2%) showed no staining. Regarding TGF-β1 staining, 18 patients (32.1%) demonstrated moderate to high staining, whereas 38 patients (67.9%) exhibited low (36/38) or no staining (2/38). A statistically significant correlation was found between TGF-β1 staining levels and ESA treatment administration (P = 0.011). Additionally, a significant relationship was observed between lower erythropoietin (EPO) levels and moderate to high TGF-β1 staining (P = 0.04). However, when TGF-β1 staining status was compared with first- and third-month treatment responses in patients receiving ESA therapy, no significant difference was detected between groups. These findings suggest that while TGF-β1 alone may not be sufficient to predict ESA treatment response, additional parameters related to the TGF-β/SMAD pathway should be considered. Strong TGF-β1 staining, alongside EPO levels, may influence the decision to initiate ESA therapy.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"1175-1183"},"PeriodicalIF":0.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohamed Badie Ahmed, Abdella M Habib, Saif Badran, Abeer Alsherawi, Fatima Al-Mohannadi, Sherouk Essam Elnefaily, Atalla Hammouda, Graeme E Glass, Ibrahem Abdalhakam, Abdul-Badi Abou-Samra, Suhail A Doi
{"title":"Hormonal predictors of the lean phenotype in humans.","authors":"Mohamed Badie Ahmed, Abdella M Habib, Saif Badran, Abeer Alsherawi, Fatima Al-Mohannadi, Sherouk Essam Elnefaily, Atalla Hammouda, Graeme E Glass, Ibrahem Abdalhakam, Abdul-Badi Abou-Samra, Suhail A Doi","doi":"10.17305/bb.2025.12209","DOIUrl":"https://doi.org/10.17305/bb.2025.12209","url":null,"abstract":"<p><p>Clinical obesity is characterized by excessive fat accumulation and an increased risk of numerous associated comorbidities. Adipose tissue secretes leptin and other adipokines, which play key roles in regulating energy balance, glucose homeostasis, and body fat mass. Recently, incretin and pancreatic hormones have also been shown to influence these processes. However, the regulatory mechanisms and interactions among these hormones are not yet fully understood. This study investigates hormonal predictors of the lean phenotype (in terms of total body fat) in patients undergoing body contouring surgery, with or without prior bariatric surgery. This prospective quasi-experimental study included patients who underwent body contouring procedures at Hamad General Hospital between January 2021 and December 2023. Patients were assessed at three time points: before surgery, 2-3 weeks post-surgery, and 6-10 weeks post-surgery. Body composition and hormone levels were measured, and statistical analyses-including descriptive statistics and logistic regression models-were used to examine trends and predict the lean phenotype. Among the hormones analyzed, amylin showed a significant association with the lean phenotype while increasing leptin, GIP and spexin levels negatively modulated the amylin effect. History of bariatric surgery weakly predicted the lean phenotype after adjusting for leptin and gut hormone levels. A margins plot demonstrated the interactions between amylin, spexin, GIP, and leptin levels that collectively predicted the probability of exhibiting the lean phenotype. These findings highlight amylin, GIP, leptin, and spexin as key hormonal predictors of fat mass, underscoring the critical role of gut hormones and adipokines in determining body fat distribution and the lean phenotype in humans.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Skin pathology in ALS: Diagnostic implications and biomarker potential.","authors":"Ying Gao, Yanchao Lu, Ranran Chen, Shumin Zhao, Jialing Liu, Sutian Zhang, Xue Bai, Jingjing Zhang","doi":"10.17305/bb.2025.12100","DOIUrl":"https://doi.org/10.17305/bb.2025.12100","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons in the spinal cord and brain, resulting in motor deficits and muscle atrophy. Approximately 5-10% of ALS patients are familial (fALS), while the rest are sporadic (sALS). Currently, early diagnosis of ALS cannot be achieved based on clinical manifestations and electromyography due to the lack of effective and easily available biomarkers. The skin and central nervous system (CNS) share the same embryonic origin. Several skin biomarkers have been found in many neurodegenerative diseases, such as abnormal deposition of pathological α-synuclein (α-Syn) in Parkinson's disease. Thus, molecular changes in the skin associated with ALS-specific pathological events could readily be detected and become biomarkers for ALS through skin testing. Here, we summarize the literature on pathological changes in the skin of ALS patients and animal models, including structural abnormalities of the skin, reduced density of skin nerve fibers, abnormal protein aggregation, altered mitochondrial morphology and function, and dysregulation of skin inflammation, which may be useful for early diagnosis and monitoring of ALS progression.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaomin Wang, Bingxu Li, Zhiyong Zheng, Weijie Wang
{"title":"Neoadjuvant immunochemotherapy for resectable esophageal cancer: A study on efficacy and safety.","authors":"Xiaomin Wang, Bingxu Li, Zhiyong Zheng, Weijie Wang","doi":"10.17305/bb.2025.11806","DOIUrl":"https://doi.org/10.17305/bb.2025.11806","url":null,"abstract":"<p><p>The combination of immunosuppressants and chemotherapy has reshaped the treatment landscape for esophageal cancer (EC). This study aimed to evaluate the effectiveness and safety of a neoadjuvant immunochemotherapy (nICT) regimen in patients with resectable EC. A total of 99 eligible patients were included. Data on patient characteristics, nICT regimens, surgical approaches, postoperative outcomes, adverse events (AEs) related to neoadjuvant therapy and surgery, overall survival (OS), and disease-free survival (DFS) were collected. OS, DFS, and safety were the primary endpoints. Cox regression analysis was used to identify prognostic factors in the overall population. Additionally, exploratory research was conducted to assess the clinical value of blood immune indicators in predicting tumor regression. Following surgery, 99.0% of patients achieved complete resection (R0). After neoadjuvant therapy, the number of patients with stage T0N0 increased, with complete or moderate responses being the most common outcomes according to American Joint Committee on Cancer (AJCC)/ College of American Pathologists (CAP)-tumor regression grading (TRG) evaluations (64.7%). The one-year OS and DFS rates were 91.6% and 49.3%, respectively. Grade ≥3 AEs related to neoadjuvant therapy occurred in 21.2% of patients, with gastrointestinal reactions being the most frequent (16 cases, 16.2%). No treatment-related deaths were reported. Grade ≥3 surgery-related AEs occurred in 10.1% of patients, with anastomotic leakage being the most common (six cases, 6.1%). Several factors were associated with significantly improved OS, including chemotherapy regimens combining paclitaxel with platinum, surgical approaches using laparoscopy or thoracotomy (left or right), an interval of ≤34 days between the last treatment and surgery, and the absence of positive lymph node detection. Higher cT staging was significantly associated with worse DFS. Blood immune markers, such as the neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) were found to predict tumor regression in EC patients. In summary, nICT demonstrated favorable effectiveness and safety in resectable EC. The choice of platinum-based chemotherapy agents, rather than the type of immunosuppressant, was associated with prognosis. Moreover, a shorter interval (≤34 days) between the final nICT administration and surgery was linked to improved outcomes.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"PF4 in rejuvenation therapy: neuroprotection and cognitive enhancement.","authors":"Li Li, Chunming Xie","doi":"10.17305/bb.2025.11960","DOIUrl":"https://doi.org/10.17305/bb.2025.11960","url":null,"abstract":"<p><p>Platelet factor 4 (PF4), a platelet-derived chemokine found in the blood, has been identified as a critical factor in modulating the rejuvenation of the aged brain. Increasing evidence suggests that PF4 secretion is a prerequisite for the cognitive benefits associated with young blood transfusion, the longevity factor klotho, and exercise. Systemic administration of exogenous PF4 has been shown to reduce circulating pro-aging immune factors and restore peripheral immune function in the aged brain by mitigating age-related hippocampal neuroinflammation, promoting molecular changes in synaptic plasticity, and improving cognitive function in aged mice. Clinically, reduced serum PF4 levels have been significantly associated with cognitive decline and core pathological biomarkers in Alzheimer's disease. Mechanistically, the chemokine receptor CXCR3 partially mediates the cellular, molecular, and cognitive benefits of systemic PF4 administration in the aged brain. However, several critical questions remain, including the potential role of PF4 in blood-brain communication, its interaction with neurotransmitters and neuropharmacological processes, and how these findings might be translated into clinical practice. Further detailed studies are needed to validate and expand upon these insights for therapeutic application.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ohood S Alharbi, Mohanned Talal Alharbi, Mazen A Ismail, Ahmad M Sait, Mohammed Mufrrih, Wafaa Alhazmi, Bandar Hasan Saleh, Manal A Zubair, Noha A Juma, Noof R Helmi, Hatoon A Niyazi, Hanouf A Niyazi, Hussam Daghistani, Taghreed Shamrani, Waiel S Halabi, Abdalbagi Alfadil, Hisham N Altayb, Karem Ibrahem
{"title":"Unveiling the synergistic power of 3-hydrazinoquinoxaline-2-thiol and vancomycin against MRSA: An <i>in vitro </i>and <i>in silico</i> evaluation.","authors":"Ohood S Alharbi, Mohanned Talal Alharbi, Mazen A Ismail, Ahmad M Sait, Mohammed Mufrrih, Wafaa Alhazmi, Bandar Hasan Saleh, Manal A Zubair, Noha A Juma, Noof R Helmi, Hatoon A Niyazi, Hanouf A Niyazi, Hussam Daghistani, Taghreed Shamrani, Waiel S Halabi, Abdalbagi Alfadil, Hisham N Altayb, Karem Ibrahem","doi":"10.17305/bb.2025.11886","DOIUrl":"https://doi.org/10.17305/bb.2025.11886","url":null,"abstract":"<p><p>Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen causing infections ranging from skin disorders to severe conditions like infective endocarditis. Its evolving resistance, including resistance to β-lactams and last-resort antibiotics, such as vancomycin, daptomycin, and linezolid, necessitates alternative therapies. This study investigates the synergistic efficacy of vancomycin and 3-hydrazinoquinoxaline-2-thiol (3HL) against 23 clinical MRSA isolates. Susceptibility testing was performed using broth microdilution and checkerboard assays, while in silico analyses assessed interactions between vancomycin and 3HL. Vancomycin exhibited minimum inhibitory concentrations (MICs) ranging from 0.25 to 1 μg/mL, whereas 3HL showed higher MICs of 16-32 μg/mL. Synergistic interactions were confirmed via checkerboard assays, with fractional inhibitory concentration index (FICI) values between 0.236 and 0.5, indicating enhanced vancomycin efficacy. Notably, vancomycin MICs decreased significantly when combined with 3HL. In silico docking revealed interactions with penicillin-binding protein 2a (PBP2a), suggesting promising therapeutic potential. Vancomycin exhibited superior docking scores (-8.9 kcal/mol) and stabilizing hydrogen bonds, effectively targeting key protein grooves. Both compounds demonstrated potential for overcoming PBP2a's structural occlusions, suggesting their role in combating β-lactam-resistant strains through targeted protein inhibition and structural stabilization.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Serum ferritin as a prognostic biomarker in CAR-T therapy for multiple myeloma: A meta-analysis.","authors":"Jing Cheng, Yuan Song","doi":"10.17305/bb.2025.12129","DOIUrl":"https://doi.org/10.17305/bb.2025.12129","url":null,"abstract":"<p><p>Serum ferritin, a marker of systemic inflammation and iron metabolism, has been implicated in the outcomes of patients with relapsed/refractory multiple myeloma (R/R MM). However, its prognostic significance in R/R MM patients undergoing chimeric antigen receptor-modified T-cell (CAR-T) therapy remains unclear. This meta-analysis aimed to evaluate the association between pre-infusion serum ferritin levels and survival outcomes in R/R MM patients treated with CAR-T therapy. We systematically searched PubMed, Embase, and Web of Science for relevant studies. Studies reporting progression-free survival (PFS) and/or overall survival (OS) based on serum ferritin levels were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Eight retrospective cohort studies, encompassing 1077 patients, met the inclusion criteria. High pre-infusion serum ferritin levels were significantly associated with worse PFS (HR: 2.15, 95% CI: 1.74-2.66, P < 0.001) and OS (HR: 2.86, 95% CI: 2.20-3.72, P < 0.001), with mild heterogeneity (I² = 9% for PFS and 0% for OS). Sensitivity analyses, conducted by excluding one study at a time, confirmed the robustness of these findings. Subgroup analyses showed consistent results across different CAR-T product sources (commercial vs academic), ferritin cutoffs, and follow-up durations (P for subgroup differences all >0.05). In conclusion, elevated serum ferritin levels before CAR-T infusion predict poorer survival outcomes in R/R MM patients. These findings highlight the potential prognostic value of ferritin and its role in optimizing patient selection and management strategies in CAR-T therapy.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lili Liu, Cheng Yang, Yan Li, Hao Zhou, Mei Shi, Tiantian Shi, Weibing Shi
{"title":"EPAS1 amplifies asthma pathogenesis through JAK2/STAT3-mediated ferroptosis and inflammation.","authors":"Lili Liu, Cheng Yang, Yan Li, Hao Zhou, Mei Shi, Tiantian Shi, Weibing Shi","doi":"10.17305/bb.2025.11334","DOIUrl":"https://doi.org/10.17305/bb.2025.11334","url":null,"abstract":"<p><p>Asthma is a chronic respiratory disorder marked by airway hyperresponsiveness and inflammation, yet the specific molecular mechanisms driving these processes remain only partially understood. This study aims to better understand how the JAK2/STAT3/EPAS1 axis regulates inflammation and ferroptosis in asthma. Asthma-related datasets were retrieved from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified. Weighted Gene Co-expression Network Analysis (WGCNA) was used to detect gene modules associated with asthma. A protein-protein interaction (PPI) network was then constructed by intersecting WGCNA-derived genes with ferroptosis-related genes to identify key hub genes. The diagnostic value of these ferroptosis-associated genes was evaluated using Receiver Operating Characteristic (ROC) curve analysis. Additionally, immune cell infiltration in asthma patients was analyzed using the Immune Cell AI database in relation to ferroptosis-related genes. Functional experiments at the cellular level were conducted to assess the effects of key genes on cell viability, inflammation, and ferroptosis. Bioinformatics analysis identified 1,698 DEGs linked to asthma. Five hub genes with clinical diagnostic value- Endothelial PAS Domain Protein 1 (EPAS1), STAT3, G6PD, CYBB, and CBS-were identified. Immune analysis revealed that EPAS1 is closely associated with immune cell infiltration in asthma. Functional experiments further demonstrated that the JAK2/STAT3 axis promotes ferroptosis and inflammatory responses by upregulating EPAS1 expression. Notably, these findings highlight the JAK2/STAT3/EPAS1 axis as a potential therapeutic target for asthma, offering new insights into its molecular mechanisms and identifying novel biomarkers for diagnosis and treatment.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jieqi Zhang, Xihan Ying, Rong Hu, Yi Huang, Ruoqi Wang, Lei Wu, Dexiong Han, Ruijie Ma, Kelin He
{"title":"Metagenomic and metabolomic analysis of gut microbiome's role in spinal cord injury recovery in rats.","authors":"Jieqi Zhang, Xihan Ying, Rong Hu, Yi Huang, Ruoqi Wang, Lei Wu, Dexiong Han, Ruijie Ma, Kelin He","doi":"10.17305/bb.2025.12164","DOIUrl":"https://doi.org/10.17305/bb.2025.12164","url":null,"abstract":"<p><p>Spinal cord injury (SCI) induces profound systemic changes, including disruptions in gut microbiome composition and host metabolism. This study aimed to investigate the impact of SCI on gut microbial diversity and serum metabolites in rats, and to explore potential microbiome-metabolite interactions that may influence recovery. Male Sprague-Dawley (SD) rats were assigned to either SCI or sham-operated groups. Fecal samples were collected for whole-genome metagenomic sequencing, and serum samples were analyzed using untargeted metabolomics. Gut microbial composition and diversity were assessed using α- and β-diversity indices, while Linear discriminant analysis effect size (LEfSe) identified differentially abundant taxa. Metabolomic pathway analysis was performed to detect significant changes in serum metabolites, and Spearman's correlation was used to evaluate associations between gut microbes and metabolites. SCI significantly altered gut microbiota composition, with increased proportions of Ligilactobacillus and Staphylococcus, and decreased proportions of Lactobacillus and Limosilactobacillus. Metabolomic analysis revealed disrupted energy metabolism and elevated oxidative stress in SCI rats, as indicated by increased serum levels of pyruvate and lactic acid. Correlation analysis further identified significant associations between specific gut bacteria and key metabolites, suggesting microbiome-driven metabolic dysregulation following SCI. These findings highlight significant interactions between the gut microbiota and host metabolism after SCI and suggest that microbiome-targeted interventions may hold therapeutic potential for improving recovery by modulating metabolic function and oxidative stress responses.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of thyroid immune-related adverse events on clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with checkpoint inhibitor therapy: A single center study.","authors":"Šejla Cerić, Timur Cerić, Emir Sokolović, Jasmina Dalač, Dragana Miletić, Inga Marijanović, Layan Mattar, Amina Aljić, Selma Agić-Bilalagić, Amera Šadija, Miran Hadžiahmetović, Semir Bešlija","doi":"10.17305/bb.2025.12321","DOIUrl":"https://doi.org/10.17305/bb.2025.12321","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for non-small cell lung carcinoma (NSCLC) but are associated with immune-related adverse events (irAEs), including thyroid dysfunction. This study examines the incidence and clinical impact of thyroid dysfunction in NSCLC patients receiving ICIs at the Clinic of Oncology, Clinical Center University of Sarajevo. In this retrospective cohort study of 50 patients with metastatic NSCLC treated with ICIs-either in combination with chemotherapy or as monotherapy for those with programmed death-ligand 1 (PD-L1) expression ≥ 50%-we collected data on demographics, treatment regimens, thyroid function tests, and survival outcomes. Thyroid dysfunction occurred in 24 patients (48%), with 12 (24%) developing hypothyroidism, 4 (8%) developing hyperthyroidism, and 8 (16%) experiencing a transition from hyperthyroidism to hypothyroidism. The incidence of thyroid dysfunction was significantly higher in patients treated with atezolizumab compared to pembrolizumab (P = 0.04), with 87.5% of affected patients receiving atezolizumab. The median time to onset of thyroid dysfunction was 10 cycles (interquartile range [IQR]: 5) for hypothyroidism and six cycles (IQR: 19) for hyperthyroidism. Progression-free survival (PFS) was significantly longer in patients who developed thyroid dysfunction, with the median PFS not reached, compared to a median PFS of 14 months (95% CI: 9.68-18.32) in patients without thyroid dysfunction (P = 0.038). No significant associations were found between thyroid dysfunction and patient age or gender. These findings suggest that thyroid dysfunction is a common irAE in patients with metastatic NSCLC receiving ICIs, particularly atezolizumab, and its development may be associated with improved PFS. Regular monitoring of thyroid function is recommended to promptly identify and manage thyroid abnormalities during ICI therapy, potentially improving patient outcomes.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}