Iranian Biomedical Journal最新文献

{"title":"Exercise-Induced Lactate Is Associated with the Modulation of Mitophagy and Ferroptosis and Reduced Amyloid-Beta and Tau in Type 2 Diabetes.","authors":"Pouria Khosravi, Fereshteh Shahidi, Arezoo Eskandari, Kayvan Khoramipour","doi":"10.22034/IBJ.30.1.67","DOIUrl":"10.22034/IBJ.30.1.67","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes (T2D) is associated with increased oxidative stress, impaired mitophagy, enhanced ferroptosis, and the accumulation of amyloid beta (Aβ) and hyperphosphorylated tau in the hippocampus. Exercise-induced lactate exerts neuroprotective effects via mitochondrial quality control and redox-regulating pathways. This study investigated whether high-intensity interval training (HIIT)-induced lactate accumulation can attenuate Aβ and tau pathology in diabetic rats by modulating mitophagy and ferroptosis-related protein signaling, as it remains unclear how HIIT-induced lactate impacts these pathways in T2D.</p><p><strong>Methods: </strong>Thirty-two male Wistar rats were assigned to control (CO), exercise (EX), diabetes (DB), and diabetes + exercise (DB+EX) groups. T2D was induced using a high-fat diet and streptozotocin (35 mg/kg). The EX and DB+EX groups performed treadmill-based HIIT (4-10 intervals at 80-100% maximum running velocity). We measured serum lactate levels and the hippocampal protein levels of MCT2, SIRT1, BDNF, p62, Keap1, NRF2, MDA, GPX4, PINK1, parkin, Aβ, and Tau using standard laboratory methods.</p><p><strong>Results: </strong>The DB group exhibited a significant increase in hippocampal oxidative stress markers and accumulation of Aβ and Tau compared to the control groups. In contrast, the DB + EX group showed elevated serum lactate levels and higher hippocampal protein levels of MCT2, SIRT1, BDNF, p62, NRF2, GPX4, PINK1, and Parkin. This group also demonstrated reduced levels of Keap1, MDA, Aβ, and Tau relative to the DB group.</p><p><strong>Conclusion: </strong>HIIT enhanced mitophagy and reduced ferroptosis in the hippocampus of T2D rats, coinciding with the activation of lactate-SIRT1-BDNF and p62-Keap1-NRF2 pathways and reduced Aβ and Tau accumulation.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":"30 1","pages":"67-80"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicles-Derived MicroRNAs: Emerging Game Changers in Cancer Pathogenesis and Therapeutic Response.","authors":"Faezeh Maroufi, Amirali Ebrahimpour, Fatemeh Davami","doi":"10.22034/IBJ.30.1.1","DOIUrl":"10.22034/IBJ.30.1.1","url":null,"abstract":"<p><p>Effective communication between cells is a fundamental feature of multicellular organisms, occurring through direct contact or the transfer of secreted molecules. Among these mediators, extracellular vesicles (EVs) function as biological messengers that transport bioactive molecules among cells. EVs are secreted by nearly all cell types. The interaction between tumor cells and EV components has been shown to influence various cancer-related processes, including proliferation, metastasis, stemness, chemoresistance, and immune modulation. Among the bioactive cargos of EVs, non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs), play a significant role in shaping the tumor microenvironment. These EV-derived ncRNAs have emerged as promising tools for non-invasive diagnosis, prognosis, and therapeutic intervention across multiple cancer types. This review summarizes the current understanding of the functional roles of EV-derived miRNAs in cancer and highlights their potential clinical applications as novel biomarkers and therapeutic targets in cancer management.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":"30 1","pages":"1-15"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin and 5-Fluorouracil Synergistically Suppress ZEB1 and Restore Epithelial Integrity in Triple-Negative Breast Cancer.","authors":"Leila Nejat, Mahdi Hatami, Maryam Adelipour, Somayeh Igder, Mojtaba Rashidi","doi":"10.22034/IBJ.30.1.47","DOIUrl":"10.22034/IBJ.30.1.47","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) remains a therapeutic challenge due to its metastatic features and resistance to conventional therapies. This study investigated the synergistic potential of quercetin (QC), a natural flavonoid, and 5-fluorouracil (5-FU) in targeting epithelial-mesenchymal transition (EMT) to inhibit proliferation and migration of the MDA-MB-231 TNBC cell line.</p><p><strong>Methods: </strong>Cytotoxicity and selectivity were assessed using the MTT assay in MDA-MB-231 cells and normal MRC-5 fibroblasts. Synergy was quantified using combination index (CI) values. Scratch assay was assessed for migration inhibition, while quantitative RT-PCR analyzed EMT-related gene expression (Vimentin, ZEB1, N-cadherin, and E-cadherin). Western blotting confirmed protein expression of ZEB1 and E-cadherin following treatment with QC (50 μM), 5-FU (25 nM), or their combination.</p><p><strong>Results: </strong>QC and 5-FU demonstrated concentration- and time-dependent cytotoxicity in MDA-MB-231 cells, with QC being highly selective for cancer cells. Toxicity in normal MRC-5 fibroblasts occurred only at 800 µM (25% viability). The combination of 50 µM of QC and 25 nM of 5-FU exhibited the strongest synergy (CI = 0.08), reducing viability by 75% and migration by 87.8%. QC alone downregulated ZEB1, Vimentin, and N-cadherin, while 5-FU further reduced these markers. Combined treatment enhanced suppression (ZEB1: 0.46-fold; Vimentin: 0.47-fold; N-cadherin: 0.68-fold) and significantly upregulated E-cadherin (3.75-fold), indicating EMT reversal. Western blotting confirmed decreased ZEB1 and increased E-cadherin by over four-fold with QC + 5-FU, indicating a shift to an epithelial phenotype.</p><p><strong>Conclusion: </strong>Combining QC and 5-FU effectively inhibited TNBC proliferation and migration while minimizing toxicity to normal cells. This dual-action strategy offers a promising low-toxicity therapeutic approach for aggressive TNBC.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":"30 1","pages":"47-58"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Epithelial-Mesenchymal Transition-Related Genes in Primary Brain Tumors.","authors":"Shiva Bayat, Negar Mousavi, Fatemeh Vand-Rajabpour, Ali Mamivand, Mina Tabrizi, Alireza Khoshnevisan","doi":"10.22034/IBJ.30.1.59","DOIUrl":"10.22034/IBJ.30.1.59","url":null,"abstract":"<p><strong>Background: </strong>Gliomas are the most common malignant primary brain tumors in adults. Meningiomas, on the other hand, are benign primary brain tumors treated by surgical resection. Epithelial-to-mesenchymal transition (EMT), stemness, and leader behavior are among the most important complex processes contributing to tumor progression and aggressiveness. Thus, the evaluation of molecular targets involved in the EMT processes in primary brain tumors can help elucidate the molecular mechanisms underlying glioma aggressiveness, ultimately identifying potential areas for further research.</p><p><strong>Methods: </strong>We conducted expression analysis of zinc finger E-box homeobox 1 (ZEB1), Sry-related HMG box (SOX2), and p21 in 31 glioma (15 glioblastoma [GBM] and 16 non-GBM) and 44 meningioma samples using quantitative real-time PCR. We also compared expression levels between glioma and meningioma, as well as between GBM and non-GBM tumor samples.</p><p><strong>Results: </strong>The expression levels of SOX2 and ZEB1 showed a significant increase in gliomas compared to meningiomas (p = 0.016 and 0.017, respectively). However, p21 did not reveal any significant difference in expression between the two groups. Notably, p21 was the only gene that exhibited a significant increase in expression in GBM samples compared to non-GBM samples, with a p value of 0.027.</p><p><strong>Conclusion: </strong>Our results suggest that SOX2 and ZEB1 expression levels have a significant role in glioma progression. Interestingly, based on the elevated p21 expression level in the GBM, we also suggest that aggressive tumor features arise from distinct molecular mechanisms depending on tumor subtype, not a single universal pathway.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":"30 1","pages":"59-66"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Metabolic Pathways in AML Cell Lines: Impact of Hypoxia-Inducible Factor-1α (HIF-1α) and Lactate Dehydrogenase-A (LDH-A) Inhibition.","authors":"Amir Kahrizi, Hossein Asgarian-Omran, Saeid Taghiloo, Reza Valadan, Ahmad Najafi, Armin Akbar, Ehsan Zaboli, Ramin Shekarriz, Mohammad Eslami-Jouybari, Mohsen Tehrani","doi":"10.61882/ibj.5155","DOIUrl":"10.61882/ibj.5155","url":null,"abstract":"<p><strong>Introduction: </strong>The Warburg effect is considered one of the most important metabolic alterations in tumor cells. While extensively studied in solid tumors, the role of this effect in acute myeloid leukemia (AML) is less defined. hypoxia inducible factor 1 alpha (HIF-1α) and lactate dehydrogenase A (LDH-A) are key regulators of glycolysis, promoting lactate production and the expression of lactate transporters. In this study, we examined the impact of HIF-1α and LDH-A inhibition on metabolic pathways, cell viability, and lactate transporter mRNA expression in AML cell lines.</p><p><strong>Methods: </strong>K-562 and HL-60 cells were treated with silibinin, an HIF-1α inhibitor, and sodium oxamate, a LDH-A inhibitor. Cell viability and apoptosis were evaluated using the MTT assay and flow cytometry, respectively. Acidification rate and LDH-A activity were assessed using lactate assay and LDH-A assay kits, respectively. Relative mRNA expression of MCT1 and MCT4 was determined using qRT-PCR.</p><p><strong>Results: </strong>Treatment with silibinin and sodium oxamate reduced proliferation and increased apoptosis in both K-562 and HL-60 cells. As expected, both agents decreased extracellular lactate release in K-562 cells, and sodium oxamate inhibited the LDH-A activity in both cell lines. Interestingly, the expression of MCT1, but not MCT4, was downregulated in K-562 cells after treatment.</p><p><strong>Conclusion: </strong>Our findings show that HIF-1α and LDH-A inhibitors not only serve as cytotoxic drugs but also regulate the expression of lactate transporter and interfere with the metabolism-related mechanisms in AML cells.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":"29 6","pages":"427-36"},"PeriodicalIF":1.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13330668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146063458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory Signaling Pathways in Ovarian Cancer Stem Cells: Their Role in Tumor Progression and Therapeutic Strategies.","authors":"Dini Amalia, Febriani Febriani, Arfianti Arfianti","doi":"10.61882/ibj.5158","DOIUrl":"10.61882/ibj.5158","url":null,"abstract":"<p><p>In ovarian cancer, ovarian cancer stem cells (OCSCs) not only contribute to tumor formation but also drive the progression, metastasis, and chemoresistance. The defining properties of OCSCs are sustained through the Wnt/β-catenin, Notch, and Hedgehog signaling pathways, which can synergize rather than act independently to form a triad that enhances key functional capabilities of OCSCs. Various therapeutic agents have been studied to target these pathways in OCSCs, including γ-secretase inhibitors (nirogacestat), smoothened inhibitors (vismodegib and sonidegib), and Wnt/β-catenin inhibitors (PRI-724 and ipafricept). While these agents have demonstrated antitumor activity in preclinical and early clinical studies, their clinical use remains challenging due to compensatory interactions among signaling pathways, which diminish the efficacy of single-agent treatments. To improve treatment outcomes, strategies involving combination approaches and personalized treatments need to be explored. This review aims to summarize current evidence on the role of Wnt/β-catenin, Notch, and Hedgehog signaling pathways in OCSCs and their therapeutic implications in ovarian cancer.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":"29 6","pages":"360-73"},"PeriodicalIF":1.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13330697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146063536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential of Stevia rebaudiana Bertoni Aquatic Extract in Treating Diabetes-Induced Infertility: Effects on Autophagy and Apoptosis.","authors":"Mozhdeh Zamani, Farhad Koohpeyma, Alireza Raeisi, Pooneh Mokarram, Sanaz Dastghaib","doi":"10.61882/ibj.5152","DOIUrl":"10.61882/ibj.5152","url":null,"abstract":"<p><strong>Background: </strong>Infertility is one of the major complications of diabetes. Diabetic-mediated oxidative stress could destroy autophagy in testes, leading to damaged sperm and male infertility. Stevia rebaudiana Bertoni is a medicinal herb with various health-beneficial effects, such as improving diabetes-induced infertility. However, till now, no exact mechanism is known for its effects on diabetic testes. This study aimed to investigate the anti-infertility role of S. rebaudiana aqueous extract in diabetic rats induced by streptozotocin (STZ) by focusing on autophagy and apoptosis pathways and antioxidant activity.</p><p><strong>Methods: </strong>Male rats were divided into four groups of five, including a healthy control group, a diabetic control (STZ) group, and metformin (MET)-treated (500 mg/kg) and stevia-treated (400 mg/kg) diabetic groups for 30 days. After the experimental period was over, rats were sacrificed. Testes tissue and blood samples were prepared for biochemical, molecular, and histopathological analyses.</p><p><strong>Results: </strong>Treatments with stevia and MET significantly increased body weight and testosterone levels and decreased FBS compared to the STZ group. Moreover, both treatments decreased the mRNA expression of Akt1, Mtor, Sqstm1/p62, Nfkb1 and caspase-9 and increased the expression of Becn1, Atg3, Atg5, Atg7, Map1lc3b/LC3B, Nrf2 and Bcl2, suggesting a possible improvement in autophagy- and apoptosis-related responses in diabetic rats. Histopathological changes and sperm characteristics also showed improvement following stevia and MET treatments.</p><p><strong>Conclusions: </strong>Stevia aqueous extract could exert potential therapeutic effects on diabetes-induced infertility in diabetic rats, possibly through the modulation of autophagy, apoptosis, and antioxidant activity.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":"29 6","pages":"413-26"},"PeriodicalIF":1.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13330655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146063475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel FKBP10 Mutation in Iranian Patients with Osteogenesis Imperfecta: Insights from Whole-Exome Sequencing to Molecular Dynamics.","authors":"Moslem Hoseinbeyki, Shirin Moradifard, Fatemeh Mirkhani, Fatemeh Sadat Shariati, Parastoo Ehsani, Mohammad Reza Alaei, Mina Ebrahimi-Rad","doi":"10.61882/ibj.5278","DOIUrl":"10.61882/ibj.5278","url":null,"abstract":"<p><strong>Background: </strong>Osteogenesis imperfecta is a rare hereditary disorder affecting bone and connective tissue. While most cases are linked to autosomal dominant mutations in the COL1A1 and COL1A2 genes, FKBP10 variants are associated with the autosomal recessive form of OI, type XI. The study represents the first cohort-based evaluation of the FKBP10 mutational spectrum in Iranian patients, leading to the discovery of a novel variant.</p><p><strong>Methods: </strong>Thirty Iranian patients clinically diagnosed with OI were enrolled for genetic analysis. WES was performed to identify pathogenic variants, validated by PCR and sanger sequencing in patients and their parents. To explore the biological relevance of the identified variants, we constructed PPI networks and performed functional enrichment analysis using the ClueGO plugin. MD simulations with GROMACS were used to assess the structural impact of the mutations.</p><p><strong>Results: </strong>Among 30 families, four exhibited pathogenic FKBP10 variants. Three patients were homozygous for the previously reported mutation (c.831dupC: p. G278Rfs95), while the fourth harbored a novel homozygous deletion (c.855_859del: p. G286Lfs84). Network analysis revealed significant involvement of CRTAP, IFITM5, SERPINF1, PPIB, FKBP10, P3H1, SERPINH1, and PLOD2 in collagen-related pathways. Computational modeling and MD simulations indicated reduced flexibility and more compact folding in the mutant FKBP10 protein, which aligns with impaired protein function and defective collagen processing.</p><p><strong>Conclusion: </strong>This study reports a novel FKBP10 variant and presents the first cohort-based analysis of FKBP10 mutations in Iranian patients with OI. It demonstrates the value of combining WES with computational modeling to elucidate the molecular mechanisms underlying OI.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":"29 6","pages":"437-50"},"PeriodicalIF":1.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional Control of PI3K/AKT/mTOR by piRNA-651 in Breast Carcinoma.","authors":"Sena Köstü, Baturalp Bakırcı, Ece Bilge Şimşek, Defne Dumanlı, Ahmetcan Çelik, Alara Kaya, Damla Kolcuoğlu, Ertuğrul Çolak, Çağrı Öner","doi":"10.61882/ibj.5229","DOIUrl":"10.61882/ibj.5229","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BC) is among the most prevalent malignancies in women worldwide, yet early diagnosis is associated with a high survival rate. The proliferation of BC is linked to the overexpression of genes within the PI3K/AKT/mTOR signaling pathway. piR-651 has been reported to be effective in the proliferation and metastasis of BC. This research sought to evaluate the impact of piR-651 inhibition on the PI3K/AKT/mTOR pathway in HUVEC, MCF-7, and MDA-MB-231 cells.</p><p><strong>Methods: </strong>Anti-piR-651 and non-target sequences were introduced into HUVEC, MCF-7, and MDA-MB-231 BC cells by lipofectamine transfection. After 48 hours, total RNA was extracted, and qRT-PCR assessed the gene expression of PI3K, AKT, and mTOR.</p><p><strong>Results: </strong>Anti-piR-651 treatment significantly increased PI3K, AKT, and mTOR gene expression in HUVECs (p < 0.001). In contrast, PI3K and mTOR expression decreased in MCF-7 and MDA-MB-231 cells (p < 0.001), while AKT expression remained unchanged in MDA-MB-231 cells (p > 0.05). Correlations between these genes varied by cell type, with significant associations observed at p < 0.05 or p < 0.01, depending on the group.</p><p><strong>Conclusion: </strong>piR-651 inhibition causes AKT to behave independently of PI3K and mTOR, particularly in MCF-7 cells, suggesting limited gene therapy potential for estrogen receptor-positive BC. Preliminary data indicate that piR-651 inhibition may reduce BC cell proliferation through effects on PI3K and mTOR.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":"29 6","pages":"397-404"},"PeriodicalIF":1.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146063597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liquid Biopsy for EGFR Mutation Detection in NSCLC: Evaluation of Plasma ctDNA and Comparison with Plasma exoDNA.","authors":"Parisa Mashayekhi, Mir Davood Omrani, Ali Dehghanifard, Adnan Khosravi, Mohammad Mehdi Jahani, Negin Khosravi","doi":"10.61882/ibj.5018","DOIUrl":"10.61882/ibj.5018","url":null,"abstract":"<p><strong>Background: </strong>Accurate detection of actionable epidermal growth factor receptor ( EGFR) mutations is essential for guiding targeted therapy in non-small cell lung cancer (NSCLC). Liquid biopsy approaches using circulating tumor DNA (ctDNA) and exosomal DNA (exoDNA) offer noninvasive alternatives for molecular profiling. This study evaluated the diagnostic performance of nested PCR combined with sanger sequencing for detecting common EGFR mutations (exon 19 deletions and the L858R point mutation) in plasma samples from Iranian NSCLC patients.</p><p><strong>Methods: </strong>In this retrospective observational study, blood samples were collected from 30 NSCLC patients with confirmed EGFR mutations. ctDNA was extracted from plasma and analyzed using nested PCR followed by sanger sequencing. Specificity was assessed in 20 EGFR–wild type NSCLC patients serving as controls. Diagnostic performance was further evaluated in relation to clinicopathological factors.</p><p><strong>Results: </strong>EGFR mutations were detected in plasma ctDNA in 63.3% of patients. Detection sensitivity was significantly associated with tumor stage but was independent of mutation subtype, age, sex, or smoking status. The assay showed high specificity, with no false positive results in control samples (95% CI: 83.9–100.0%). Although exoDNA analysis demonstrated a higher sensitivity than ctDNA (76.6% vs. 63.3%), this difference was not statistically significant. Notably, combined analysis of ctDNA and exoDNA increased overall detection sensitivity to 80%.</p><p><strong>Conclusions: </strong>Nested PCR with sanger sequencing represents a reliable rule in strategy for EGFR mutation detection in plasma. Integrating ctDNA and exoDNA analyses substantially improves sensitivity and may enhance noninvasive molecular diagnostics in NSCLC.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":"29 6","pages":"405-12"},"PeriodicalIF":1.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13330677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}