Clinical And Experimental Medicine[JOURNAL]
Sun
200 papers
Screening and validation of potential molecular markers for colorectal cancer: based on bioinformatics analysis and machine learning.
Chang Y, Bai M, Liu Y … +2 more , Bai K, Hu Y
Clin Exp Med · 2026 Feb · PMID 41723787 · Full text
Colorectal Cancer (CRC) exhibits persistently high incidence and mortality rates worldwide, imposing a substantial socioeconomic burden. Early screening, early diagnosis, and early treatment can significantly improve pat...
Colorectal Cancer (CRC) exhibits persistently high incidence and mortality rates worldwide, imposing a substantial socioeconomic burden. Early screening, early diagnosis, and early treatment can significantly improve patients’ survival rates while reducing mortality. However, there remains a lack of effective biomarkers to aid in early screening and diagnosis. As a branch of artificial intelligence, machine learning can automatically analyze large volumes of data, greatly saving human time and resources. The advancement of high-throughput sequencing technology has provided researchers with abundant gene expression data, offering rich data resources for the training and validation of machine learning models. With the development of artificial intelligence, integrating knowledge from bioinformatics, machine learning, molecular biology, and clinical medicine for analysis enables a more comprehensive understanding and exploration of the molecular biological mechanisms underlying CRC. In summary, this project aims to utilize machine learning techniques to screen five CRC signature genes (ABCG2, SCGN, USP2, CLDN1, and EPHX4) from GEO datasets, validate these signature genes using TCGA database, and perform RT-qPCR to detect the relative mRNA expression levels of these genes in CRC. Ultimately, this study seeks to provide novel biomolecular markers for the early diagnosis of CRC.
When cold complicates: the impact of cryoglobulins and pre-analytical conditions on monoclonal protein analysis.
Cunningham A, Rotteveel D, Scherrenburg J … +7 more , Jacobs JFM, van Aggelen D, van Uum-Otters M, Vlot AJ, Verheggen R, Ruinemans-Koerts J, Oostendorp M
Clin Exp Med · 2026 Feb · PMID 41723782 · Full text
Cryoprecipitation of monoclonal protein in two patients from separate hospitals led to falsely reduced concentrations. In one case, this was only later discovered because the hematology analyzer falsely flagged the cryog...
Cryoprecipitation of monoclonal protein in two patients from separate hospitals led to falsely reduced concentrations. In one case, this was only later discovered because the hematology analyzer falsely flagged the cryoglobulins as abnormal platelets and lymphocytosis. This resulted in the generation of a peripheral blood smear in which the cryoprecipitation was microscopically identified. In both cases, initially unnoticed discrepancies existed between the total immunoglobulin and albumin concentrations derived from the general chemistry analyzer and those from serum protein electrophoresis analysis, which is what later alerted staff to the second case. These cases highlight the significant risk cryoglobulins pose in the diagnosis and accurate follow-up of plasma cell dyscrasias. We therefore propose several measures to improve laboratory detection and prevention of such discrepancies. These include; performing total immunoglobulin and albumin measurements alongside the protein electrophoresis analysis; implementation of a cross reference alarm in the laboratory information system for the discrepancies; consequent visual inspection of all samples prior to analysis; pre-warming of samples with a visible cryoprecipitate prior to serum protein electrophoresis; and the implementation of adequate operating procedures for handling samples from patients with known cryoglobulins to prevent pre-analytical loss caused by precipitation. Finally, we provide insight into the stability of immunoglobulins and monoclonal proteins at room temperature, which may be helpful to determine the optimal sample storage temperature in order to reduce the risk of unwanted cryoprecipitation.
Oxygen-dependent modulation of the human complement system during acute normobaric hypoxia: a translational plasma proteomics study.
Lang A, Pang TY, Piel S … +14 more , Oehler D, Zweck E, Shahrjerdi K, Okkasian M, Georgy J, Reinders Y, Duplessis AJ, Tank J, Jordan J, Pfeiler S, Sickmann A, Kelm M, Jung C, Gerdes N
Clin Exp Med · 2026 Feb · PMID 41721929 · Full text
Acute hypoxia triggers multiple physiological and immune responses, yet the immediate systemic effects on circulating complement proteins remain insufficiently characterized. The complement cascade plays a central role i...
Acute hypoxia triggers multiple physiological and immune responses, yet the immediate systemic effects on circulating complement proteins remain insufficiently characterized. The complement cascade plays a central role in inflammation, host defense, and ischemia-related tissue injury, but its regulation during transient oxygen deprivation and reoxygenation in humans is poorly understood. Sixteen healthy volunteers were exposed to stepwise normobaric hypoxia simulating altitudes of 0, 2, 4, and 6 km (pO₂ = 9.64 kPa) followed by reoxygenation under normoxic conditions. Blood samples were collected at baseline, peak hypoxia (6 km), and after reoxygenation. Quantitative plasma proteomics was performed using targeted multiple-reaction-monitoring mass spectrometry to quantify key complement components (C1 complex, C3–C9, factor B) in 16 participants with complete datasets. Hematological parameters were analyzed in parallel. Hypoxia transiently increased leukocyte and platelet count, whereas hematocrit and mean corpuscular volume slightly decreased. While only slightly increasing during hypoxia, most complement peptides - including C1S, C1R, C3, C5, C7, C9, and CFAB - showed a coordinated reduction in relative abundance upon reoxygenation compared to both baseline and hypoxia (median fold-change ≈ 0.6–0.8; p < 0.05). Correlation analysis revealed coherent clustering among complement components but only weak associations with hematological indices. Acute hypoxia elicits rapid and reversible changes in the circulating complement peptide pool in healthy humans. Targeted plasma proteomics demonstrates clear oxygen-phase–dependent dynamics, with a coordinated decrease after reoxygenation. This pattern is consistent with reduced circulating availability of complement components, activation-associated consumption, and/or redistribution within the intravascular compartment. Future validation of these findings in certain patient cohorts may define translational relevance and functional consequences.
A proteomics approach to identify predictive blood biomarkers for pleural mesothelioma in prospective cohorts.
Herman EJ, Allione A, Viberti C … +24 more , Manfredi M, Russo A, Sana-Hafeez K, Kaiser N, Johnen G, Brüning T, Mirabelli D, Dianzani I, Agudo A, Weiderpass E, Simeon V, Kaaks R, Turzanski-Fortner R, Tumino R, Milani L, Gálvez-Navas JM, Schulze MB, Schiborn C, Castro NC, Masala G, Guevara M, Vineis P, Casalone E, Matullo G
Clin Exp Med · 2026 Feb · PMID 41714836 · Full text
BACKGROUND: Pleural mesothelioma (PM) is a rare, asbestos-linked cancer with a long asymptomatic latency, delaying diagnosis and limiting treatment options. Identifying blood‐based biomarkers that signal disease before s...
BACKGROUND: Pleural mesothelioma (PM) is a rare, asbestos-linked cancer with a long asymptomatic latency, delaying diagnosis and limiting treatment options. Identifying blood‐based biomarkers that signal disease before symptoms onset could improve surveillance of at‐risk individuals. METHODS: In our work, we conducted a prospective proteomic study of pre-diagnostic serum from 21 PM cases (< 5 years before diagnosis) and 21 asbestos‐exposed controls in the EPIC cohort using SWATH‐MS, followed by ELISA validation. Findings were tested in an independent MoMar cohort of 32 pre‐diagnostic plasma samples (< 1 year before diagnosis) and 32 matched controls. RESULTS: SWATH-MS identified 12 differentially expressed proteins (nominal p < 0.05, fold change > 1.3 or < 0.75). Transferrin and complement C4A were elevated, while beta‐2‐microglobulin and dermcidin were reduced in pre‐diagnostic cases. ELISA confirmed a borderline significant rise in beta‐2‐microglobulin within two years of diagnosis in EPIC. Calretinin and mesothelin were also detected in both cohorts, with the five‐marker panel achieving an AUC of 0.91 (p = 0.001) in MoMar but not reaching significance in EPIC (AUC = 0.88, p = 0.17). CONCLUSIONS: Integrating novel proteomic biomarker candidates with established markers enhances early PM detection in high-risk populations. Larger, multi‐cohort validation is warranted to refine this biomarker panel for clinical surveillance.
An odyssey of monoclonal gammopathies: focusing on precursors and the progression from MGUS and SMM to multiple Myeloma, with a brief overview of novel therapeutic strategies.
Xin X, Fan C, Sheng R … +7 more , Li X, Zhu X, Huang Y, Seraji HR, Urazbaeva D, Atamuratova Z, Ubaydullaevna AD
Clin Exp Med · 2026 Feb · PMID 41706224 · Full text
Monoclonal gammopathies span a continuum from monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) to overt multiple myeloma (MM). This gradual clonal evolution is driven by pri...
Monoclonal gammopathies span a continuum from monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) to overt multiple myeloma (MM). This gradual clonal evolution is driven by primary cytogenetic lesions, secondary genomic events, and epigenetic remodeling within a permissive bone-marrow microenvironment. Traditional biomarkers (serum M-protein and free-light-chain ratios) provide useful but incomplete prognostic information because they do not capture spatial heterogeneity or temporal clonal dynamics. Recent advances highlight circulating tumor cells (CTCs), minimal residual disease (MRD) assessment via next-generation flow (NGF) and sequencing (NGS), and liquid biopsy approaches as minimally invasive tools that refine risk stratification and anticipate malignant progression. Therapeutic paradigms have shifted from melphalan-based chemotherapy and autologous stem cell transplantation to triplet and quadruplet combinations incorporating immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies, while next-generation immunotherapies, BCMA-directed CAR-T cells, bispecific antibodies, and cereblon E3 ligase modulators, offer unprecedented depth of response. Yet major challenges persist, including predicting individual progression in precursor states, overcoming drug resistance and relapse, managing therapy-associated toxicities, and ensuring access to advanced therapies across heterogeneous patient populations. Integrating multi-omics profiling, artificial intelligence (AI)-based analytics, and dynamic biomarkers promises to transform the natural history of these disorders, shifting the trajectory of monoclonal gammopathies from inevitable progression toward durable remission and potential cure. This review delineates the biological continuum underpinning disease progression from MGUS and SMM to MM, and provides a concise overview of recent advances in molecular diagnostics and novel therapeutic strategies within this context.
Subclinical cardiac dysfunction in idiopathic inflammatory myopathies: the role of global longitudinal strain.
Romano S, Sartorio A, Pont CD … +7 more , Segatta F, Piazzola M, Vicardi M, Cominacini M, Aldegheri F, Bixio R, Viapiana O
Clin Exp Med · 2026 Feb · PMID 41703097 · Full text
Autoimmune diseases are characterized by systemic inflammation that can affect multiple tissues. In idiopathic inflammatory myopathies (IIM), skeletal muscle is primarily involved; however, subclinical cardiac dysfunctio...
Autoimmune diseases are characterized by systemic inflammation that can affect multiple tissues. In idiopathic inflammatory myopathies (IIM), skeletal muscle is primarily involved; however, subclinical cardiac dysfunction may also occur. While left ventricular ejection fraction (EF) is commonly used to assess cardiac function, global longitudinal strain (GLS) has proven more sensitive in detecting early myocardial impairment. This study aimed to evaluate left ventricular GLS (LV GLS) in patients with IIM and no known cardiovascular disease, assessing both the prevalence of reduced GLS values and their associations with clinical and laboratory parameters. We enrolled 37 outpatients from the Department of Internal Medicine at the University Hospital of Verona, who underwent comprehensive clinical and echocardiographic assessment. The mean GLS value observed (- 17.9% ± 2.2%) was below the normal reference range (- 18.2% to - 21.2%) defined by the echocardiographic system. When compared with 37 healthy controls, IIM patients showed significantly impaired GLS despite preserved EF in both groups (- 17.88 ± 2.23% vs. - 19.88 ± 1.72%, p < 0.001). This difference remained significant after adjusting for age and sex (β = +2.25%, p < 0.001). In linear regression models, GLS was independently associated with arthritis (β = 2.165, p = 0.007), lymphocyte count (β = 0.001, p = 0.025), CK levels (β = 0.000, p = 0.024), and age (β = 0.032, p = 0.020). Patients with arthritis showed significantly worse GLS values compared to those without arthritis, despite similar EF. In multivariate analysis, arthritis remained independently associated with impaired GLS and lower CK levels. Overall, our findings suggest that patients with IIM exhibit a global reduction in left ventricular longitudinal function, detectable by GLS, even in the absence of overt cardiac disease. This impairment appears particularly evident in patients presenting with arthritis and is independent of age-related effects. Longitudinal studies are warranted to investigate the progression of GLS alterations and their potential role in guiding therapeutic strategies.
Prognostic significance of tumor fraction in advanced sarcoma: highlighting a novel circulating biomarker.
Taleb S, Brunet M, Belcaid L … +7 more , Bahleda R, Verret B, Cesne AL, Peyraud F, Spalato-Ceruso M, Toulmonde M, Italiano A
Clin Exp Med · 2026 Feb · PMID 41699340 · Full text
Circulating tumor DNA (ctDNA) tumor fraction (TF), the proportion of ctDNA within total cell-free DNA, is emerging as a simple and powerful biomarker across cancers. While recent studies in carcinomas established its pro...
Circulating tumor DNA (ctDNA) tumor fraction (TF), the proportion of ctDNA within total cell-free DNA, is emerging as a simple and powerful biomarker across cancers. While recent studies in carcinomas established its prognostic value, its role in sarcomas remains unknown. We analyzed 192 patients with advanced soft tissue sarcomas enrolled in the French BIP (NCT02534649) and STING (NCT04932525) precision medicine programs, using the FoundationOne Liquid CDx assay to quantify TF. Patients were stratified at a 10% cutpoint, consistent with prior reports. Median overall survival was 6.3 months for patients with TF ≥ 10% compared to 12.9 months for those with TF < 10% (p = 0.01). On multivariate analysis adjusting for histology, grade, performance status, and metastatic burden, high TF remained an independent predictor of poor survival (HR 2.0, 95% CI 1.1-3.5, p = 0.017). Unlike carcinomas, sarcomas currently lack validated circulating biomarkers. Our findings demonstrate that ctDNA TF provides non-invasive, real-time prognostic information in this rare and heterogeneous tumor type, with potential applications for patient stratification, treatment planning, and clinical trial design. Prospective validation is warranted to define standardized TF thresholds and support its integration into sarcoma care.
Research progress on the correlation between OPN and immune escape of gastric cancer.
Qu F, Wu S, Yu W
Clin Exp Med · 2026 Feb · PMID 41697520 · Full text
In recent years, immunotherapy represented by programmed death receptor 1 (PD-1) inhibitors has significantly improved the prognosis of patients with gastric cancer, making the immunotherapy of gastric cancer a focus of...
In recent years, immunotherapy represented by programmed death receptor 1 (PD-1) inhibitors has significantly improved the prognosis of patients with gastric cancer, making the immunotherapy of gastric cancer a focus of clinical attention. Although immune checkpoint inhibitors (ICIs) have achieved breakthroughs in immunotherapy, only a portion of patients have achieved promising long-term results in response to checkpoint inhibitors, indicating the existence of other unknown tumor-induced immunosuppressive pathways. The failure of immunotherapy is mainly related to the induction of immune tolerance in the tumor microenvironment of gastric cancer. Therefore, solving the problem of tumor immune tolerance is the key to the success of immunotherapy for gastric cancer. Studies have found that OPN promotes tumor progression through multiple mechanisms such as influencing tumor cell survival, tumor angiogenesis, and regulating the tumor microenvironment. For this purpose, we review the role of OPN in the occurrence and development of gastric adenocarcinoma, and focus on reviewing the current research progress of OPN in inducing immune escape of gastric adenocarcinoma and the synergistic effect between OPN and PD-L1 and its potential mechanisms, laying the foundation for the development of immunotherapy combination methods based on OPN in future.
The role of tumor-associated macrophages in cancer development and their significance as prognostic markers.
Salmaninejad A, Layeghi SM, Falakian Z … +5 more , Foroushani PS, Golestani S, Pourghazi F, Kobravi S, Yousefi M
Clin Exp Med · 2026 Feb · PMID 41697492 · Full text
Macrophages are a diverse group of immune cells which have key roles in immune defense, tumor homeostasis, and wound repair. During the last two decades, the role of macrophages as one of the most abundant tumor-infiltra...
Macrophages are a diverse group of immune cells which have key roles in immune defense, tumor homeostasis, and wound repair. During the last two decades, the role of macrophages as one of the most abundant tumor-infiltrating stromal cells has gradually emerged. The normal function of these tumor-associated macrophages (TAMs) in tumor microenvironment (TME) is to suppress tumor cells through triggering both direct cell cytotoxicity and antibody-mediated immune response. However, they have also been implicated in the progression of cancers. Tumor cells produce chemokines that polarize macrophages into tumor-promoting TAMs. This is the reason why the accumulation of TAMs in TME is correlated with poor prognosis in cancer patients. High plasticity of TAMs makes it feasible to regulate their polarization and adjust the balance between the anti-tumor TAMs and those with pro-tumor phenotypes. In this review, we aim to provide an overview about the origin and polarization of TAMs and their significance as biomarkers for the prediction and prognostication of various cancers.
MLANA is a potential prognostic biomarker and correlated with immune infiltration in skin cutaneous melanoma.
Tang N, Lai X, Wen W … +2 more , Wu Y, Xiong X
Clin Exp Med · 2026 Feb · PMID 41697477 · Full text
Skin cutaneous melanoma (SKCM) is an aggressive and life-threatening skin cancer arising from the malignant transformation of melanocytes. The incidence has risen in recent decades, significantly impacting patients’ qual...
Skin cutaneous melanoma (SKCM) is an aggressive and life-threatening skin cancer arising from the malignant transformation of melanocytes. The incidence has risen in recent decades, significantly impacting patients’ quality of life and straining healthcare systems. Existing prognostic biomarkers for SKCM are not accurate enough, emphasizing the urgent need for new biomarkers and therapeutic targets. This study comprehensively explored the role of Melan-A (MLANA) in SKCM through bioinformatics analysis and in-vitro experiments. Results showed that MLANA is overexpressed in SKCM tissues, significantly linked to Breslow depth, and associated with poor patient prognosis. Functional assays revealed that interfering with MLANA expression inhibits melanoma cell proliferation, migration, and invasion, while inducing apoptosis and G1/S phase arrest. Immune infiltration analysis revealed a negative correlation between high MLANA expression and the infiltration levels of various immune cells, indicating that MLANA may facilitate SKCM progression by altering the tumor microenvironment. The study highlights MLANA’s biological importance in SKCM, suggesting its potential as a prognostic biomarker and immunotherapy target, thereby providing new insights for SKCM diagnosis and treatment.
The safety and efficacy of bispecific T-cell engagers (TCEs) in patients with glioma.
Robat-Jazi B, Lorestani P, Nejati N … +7 more , Ebrahimi E, Habibi MA, Ahmadpour M, Jokar-Derisi A, Karimizadeh Z, Bagheri K, Ahmadpour S
Clin Exp Med · 2026 Feb · PMID 41689667 · Full text
Among the most aggressive and resistant tumors of the central nervous system, glioblastoma (GBM) has a poor prognosis and few available treatments. Because of the tumor's infiltrative nature, immunosuppressive environmen...
Among the most aggressive and resistant tumors of the central nervous system, glioblastoma (GBM) has a poor prognosis and few available treatments. Because of the tumor's infiltrative nature, immunosuppressive environment, and resistance mechanisms, traditional treatments such as radiotherapy, chemotherapy, and surgery offer only modest survival benefits. Bispecific T-cell engagers (TCEs) have shown promising preclinical and early clinical results, and immunotherapy has become a feasible strategy. TCEs efficiently promote antigen evasion and strong tumor lysis by directing cytotoxic T lymphocytes (CTLs) to tumor-associated antigens (TAA) such as the EGFRvIII ligands IL-13Rα2, Fn14, and NKG2D ligands (NKG2DLs). Although phase I clinical studies with AMG 596 have shown acceptable safety profiles and early indications of efficacy, preclinical mice have demonstrated prolonged longevity. However, challenges still exist, including the short half-life of TCEs molecules, limited T-cell infiltration, antigen heterogeneity, and the risk of neurotoxicity or cytokine release syndrome (CRS). Promising developments include novel approaches such as multivalent targeting, DNA-encoded or cell-delivered TCEs, and combinations with immune checkpoint inhibitors (ICIs) or CAR-T cells. With an emphasis on its integration into multimodal treatment approaches, this review highlights the safety, effectiveness, and potential uses of TCEs immunotherapy for gliomas.
The immunomodulatory power of mesenchymal stem/stromal cell-derived extracellular vesicles in bone disorders: A comprehensive review.
Akbarzadeh A, Farrokhi MR, Ayati Firoozabadi M … +5 more , Mortazavi SMJ, Mortazavi J, Vakili S, Shapoori S, Jafarinia M
Clin Exp Med · 2026 Feb · PMID 41689665 · Full text
Bones are not only mechanical structures but also highly active immunological organs. The bone marrow hosts hematopoietic, mesenchymal, and immune cells that continuously interact to coordinate bone remodeling, hematopoi...
Bones are not only mechanical structures but also highly active immunological organs. The bone marrow hosts hematopoietic, mesenchymal, and immune cells that continuously interact to coordinate bone remodeling, hematopoiesis, and systemic immune responses. Disruption of this osteoimmune network contributes to pathological conditions such as delayed fracture healing, osteoporosis, osteoarthritis, osteomyelitis, and other bone-destructive disorders. Mesenchymal stem/stromal cell-derived extracellular vesicles (MSC-EVs) have emerged as key paracrine mediators and promising therapeutic candidates within this system. In this review, we summarize current knowledge on the biogenesis, composition, and characterization of MSC-EVs, and then focus on how they modulate macrophages, neutrophils, T and B cells, natural killer (NK) cells, and other stromal populations in the bone microenvironment. We discuss preclinical evidence across major bone disorders, including fracture repair, osteoporosis, osteoarthritis, osteonecrosis, periodontitis, and osteomyelitis, emphasizing the immunomodulatory mechanisms involved (e.g., regulation of M1/M2 balance, Th17/Treg ratios, neutrophil extracellular traps, and NK cell activity). Finally, we outline translational progress, including early clinical studies, manufacturing and potency-assay challenges, and outstanding questions that must be addressed to integrate MSC-EVs into future therapeutic strategies for bone disease.
Translational immunothrombosis in autoimmune Heparin-Induced thrombocytopenia: targeting the FcγRIIa-Syk-BTK and complement pathways.
Ahmadinia M, Askarzade A, Afsharara H … +3 more , Gholizadeh Niari B, Jamali F, Farasatinasab M
Clin Exp Med · 2026 Feb · PMID 41689663 · Full text
Autoimmune heparin-induced thrombocytopenia (aHIT) represents a severe variant of immune-mediated thrombocytopenias (IMTs) in which anti-platelet factor 4 (PF4) antibodies activate platelets independently of heparin, lea...
Autoimmune heparin-induced thrombocytopenia (aHIT) represents a severe variant of immune-mediated thrombocytopenias (IMTs) in which anti-platelet factor 4 (PF4) antibodies activate platelets independently of heparin, leading to both thrombosis and thrombocytopenia. Despite its clinical significance, aHIT remains poorly understood and lacks evidence-based immunomodulatory treatments. This narrative translational review integrates mechanistic and therapeutic insights from immune thrombocytopenia (ITP) and antiphospholipid syndrome (APS) to identify shared pathogenic pathways relevant to aHIT. Literature from 2015 to 2025 was analyzed across PubMed, Scopus, Web of Science, and ClinicalTrials.gov, focusing on FcγRIIa-Syk-BTK signaling and complement activation as central drivers of platelet activation and clearance. Preclinical and clinical data indicate that targeting these axes with Syk inhibitors (fostamatinib), BTK inhibitors (rilzabrutinib, zanubrutinib), and complement inhibitors (sutimlimab) can restore platelet counts and mitigate immune-driven thrombosis. These findings underscore the therapeutic potential of pathway-specific interventions in aHIT, highlighting the need for biomarker-guided, translational trials to validate their efficacy and safety. Bridging mechanistic evidence from ITP and APS provides a framework for precision immunotherapy in autoimmune HIT.
Innovative combinatory approaches with dendritic cell-based vaccines: bridging preclinical insights and clinical challenges.
Motallebzadeh Khanmiri J, Khani-Eshratabadi M, Seyedmoharrami F … +7 more , Khazaee-Nasirabadi MH, Dehdashti M, Seddighi N, Peymaninezhad F, Khiabani A, Khanahmad A, Baradaran B
Clin Exp Med · 2026 Feb · PMID 41689608 · Full text
Dendritic cell (DC)-based vaccines have emerged as a promising and innovative approach in the immunotherapy of both solid tumors and hematologic malignancies. Owing to their unique capacity to present antigens and activa...
Dendritic cell (DC)-based vaccines have emerged as a promising and innovative approach in the immunotherapy of both solid tumors and hematologic malignancies. Owing to their unique capacity to present antigens and activate tumor-specific T cell responses, DC vaccines play a pivotal role in counteracting tumor immune evasion. Despite significant advances in vaccine development, several challenges - including the immunosuppressive tumor microenvironment, the complexities of designing optimal vaccines, and the difficulty of translating preclinical successes into consistent clinical outcomes - have limited their widespread effectiveness. This review highlights recent combinatory strategies aimed at enhancing the design and application of DC-based vaccines. These include the incorporation of neoantigens, tumor lysates, mRNA platforms, DC-tumor fusion constructs, and combination therapies involving immune checkpoint inhibitors and CAR-T cells. Furthermore, we examine the translational barriers that hinder the clinical implementation of these approaches and explore future directions for improving efficacy, safety, and personalization of DC vaccines. DC-based vaccines may be more effectively positioned to yield substantial and durable clinical advantages in standard oncology practice when these combinatorial strategies are integrated with rational clinical trial design, biomarker-informed patient selection, and rigorous compliance with manufacturing and regulatory standards. Ultimately, individualized and multifaceted strategies are expected to hold the greatest promise for improving therapeutic outcomes while minimizing adverse effects.
CHD4 epigenetically coordinates genomic instability and immunosuppression to drive pan-cancer progression and confer HDAC inhibitor sensitivity.
Fu G, Tao Y, Feng K … +5 more , Chen Y, Zhang W, Zhang Z, Hu G, Ou Y
Clin Exp Med · 2026 Feb · PMID 41680566 · Full text
Chromodomain Helicase DNA-Binding Protein 4 (CHD4), the core ATPase subunit of the nucleosome remodeling and deacetylation (NuRD) complex, is a key epigenetic regulator. However, a systematic pan-cancer perspective on it...
Chromodomain Helicase DNA-Binding Protein 4 (CHD4), the core ATPase subunit of the nucleosome remodeling and deacetylation (NuRD) complex, is a key epigenetic regulator. However, a systematic pan-cancer perspective on its functions, particularly its coordinated regulation of genomic stability alongside the tumor immune microenvironment, remains lacking. This study performed an integrated multi-omics analysis using data from The Cancer Genome Atlas (TCGA) and complementary genomic databases. This included systematic profiling of CHD4 expression, genomic alterations, and clinical associations across cancers. We investigated its correlations with markers of genomic instability, immune cell infiltration, and therapy response. Functional enrichment and pharmacogenomic analyses were conducted, supported by in vitro validation in osteosarcoma models. CHD4 was frequently upregulated across multiple cancer types, and its elevated expression was associated with poorer patient prognosis in several malignancies. Pan-cancer analysis revealed that high CHD4 expression correlated significantly with markers of genomic instability, such as homologous recombination deficiency (HRD) and loss of heterozygosity (LOH), and concurrently with an immunosuppressive tumor microenvironment—characterized by reduced CD8 + T cell infiltration and elevated expression of immune checkpoint molecules. Mechanistically, CHD4 expression was closely linked to core components of the NuRD complex, including HDAC1 and HDAC2, suggesting its involvement in chromatin compaction and transcriptional regulation associated with these phenotypes. Furthermore, tumors exhibiting high CHD4 expression showed increased sensitivity to histone deacetylase (HDAC) inhibitors, including vorinostat and panobinostat. This study establishes CHD4 as a pan-cancer epigenetic regulator whose expression is linked to both genomic instability and immune suppression. Furthermore, CHD4 shows promise as a predictive biomarker for sensitivity to HDAC inhibitors, highlighting its potential as a biomarker for guiding epigenetics-based therapeutic strategies.
Clinical and genetic insights into novel TP53 mutations in De Novo AML patients.
Akram AM, Hayat S, Yousaf H … +8 more , Sarwar N, Tahir A, Ali S, Yaqoob F, Zafar A, Hassan HM, Dabiellil M, Khan MIU
Clin Exp Med · 2026 Feb · PMID 41677935 · Full text
This study intended to uncover any potential variations in TP53 gene particularly the exons 3–7 as this region is reported to have abundant oncogenic variations with adverse impacts on its structural stability and functi...
This study intended to uncover any potential variations in TP53 gene particularly the exons 3–7 as this region is reported to have abundant oncogenic variations with adverse impacts on its structural stability and functional activities. The selected region of TP53 was amplified in ninety de novo AML patients and amplicons were Sanger sequenced to analyze possible nucleotide variations. Ten (10) mutations were found in the coding region of the TP53 exons 3–7 which are unique to the regional mutation data in AML patients. Further evaluation of identified variants by employing multiple bioinformatics techniques revealed likely hazardous impacts of majority of them due to their existence in the core DNA binding domain. Clinical features with the exception of platelet count did not differ significantly among the AML patients within TP53 wild type and TP53 mutant groups. Concurrently, no statistically considerable difference was observed in event free survival (EFS) (p = 0.67, HR = 1.222) or overall survival (OS) (p = 0.74, HR = 0.837) comparing two groups.
HBV reprograms the tumor microenvironment in hepatocellular carcinoma: mechanisms and therapeutic implications.
Shen X, Huang H, Sheng J … +1 more , Tang X
Clin Exp Med · 2026 Feb · PMID 41673369 · Full text
Hepatitis B virus (HBV) infection is an important worldwide health issue and attribute to hepatocellular carcinoma (HCC) via direct oncogenic and indirect mechanisms. HBV reprograms the tumor microenvironment (TME) throu...
Hepatitis B virus (HBV) infection is an important worldwide health issue and attribute to hepatocellular carcinoma (HCC) via direct oncogenic and indirect mechanisms. HBV reprograms the tumor microenvironment (TME) through immunosuppression, metabolic adaptation, and stromal remodel, allowing tumor promotion and immune evasion. This review examines HBV-induced TME changes, including epigenetic dysregulation, immune cell dysfunction, and fibrosis, as well as new therapeutic options including immune checkpoint blockade, adoptive cell therapy, and metabolic targeting to improve outcomes in HBV-related HCC.
Immunological mechanisms of autoimmune gastritis.
Qian J, Hu Z, Xu Z … +4 more , Yuan S, Zhao J, Shi H, Wang X
Clin Exp Med · 2026 Feb · PMID 41670890 · Full text
Autoimmune gastritis (AIG) is a chronic disease characterized by specific immune damage to the gastric mucosa. Previous studies have mostly focused on the single immune pathway mainly mediated by T cells, but the synergi...
Autoimmune gastritis (AIG) is a chronic disease characterized by specific immune damage to the gastric mucosa. Previous studies have mostly focused on the single immune pathway mainly mediated by T cells, but the synergistic role of humoral immunity in disease progression cannot be ignored. This article systematically reviews the immunological mechanism of AIG, and analyzes the inflammatory cascade immune mechanism centered on the self-attack of gastric parietal cells mediated by CD4 T, with the pro-inflammatory roles of Th1/Th17 cells and defective suppressive function of Tregs as a supplement. This article emphasizes the imbalance between humoral and cellular immunity, including the pathogenic potential of autoantibodies and the synergistic role of T-B cells in promoting inflammation. Furthermore, while existing animal models (including genetic modification, lymphopenic, and non-lymphopenic models) can replicate features of human AIG such as gastric gland atrophy, they exhibit significant limitations regarding the mechanism of T-B cell collaboration, differences in cancer risk, and species specificity. This article systematically clarifies that AIG results from an imbalance between cellular and humoral immunity, providing a theoretical basis for targeted immunotherapy strategies.
Identification and validation of the protective gene BCAT2 related to amino acid metabolism in idiopathic pulmonary fibrosis.
Zhu H, Chen M, Li Q … +7 more , Cui S, Jiang C, Ye X, Hou S, Zhang J, Huang X, Cao M
Clin Exp Med · 2026 Feb · PMID 41665823 · Full text
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease, with unknown pathogenesis and no effective treatment. Identifying the key molecular of IPF in underlying mechanisms is critical for developing...
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease, with unknown pathogenesis and no effective treatment. Identifying the key molecular of IPF in underlying mechanisms is critical for developing targeted therapies. Differentially expressed genes (DEGs) were identified based on GSE53845 data from the Gene Expression Omnibus (GEO) database and the Limma R package, followed by gene set enrichment analysis (GSEA). The key module genes selected by Weighted Gene Co-expression Network Analysis (WGCNA) were integrated with the DEGs. The hub genes were screened using three machine-learning algorithms, with further performance validated through Receiver Operating Characteristic (ROC) curves and nomogram models. In addition, validation was performed using external validation sets, in vitro experiments and human lung tissues. Enrichment analyses were conducted using GeneMANIA and GSEA. Branched chain amino acid transferase 2 (BCAT2) was identified as a central hub gene in IPF by intersecting key module genes with DEGs through WGCNA and machine learning methods. Experimental validation confirmed the significantly downregulation of BCAT2 in the lung tissues of IPF patients and in TGF-β1-treated alveolar epithelial cells (AECs). Moreover, upregulation of BCAT2 attenuated the expression of fibrosis markers in AECs exposed to TGF-β1. Ultimately, Co-expression analysis and GSEA indicated that BCAT2 is closely involved in several key signaling pathways. Collectively, our findings suggest that BCAT2 is a critical protective molecule in the pathogenesis of IPF and represents a potential therapeutic target for modulating the progression of pulmonary fibrosis.
Machine learning, whole-transcriptome and integrative omics analysis reveals key regulatory networks governing human spermatogonial stem cells.
Hashemi Karoii D, Osanloo M, Azizi H … +1 more , Skutella T
Clin Exp Med · 2026 Feb · PMID 41665764 · Full text
Spermatogenesis—the process of sperm cell development—is highly dependent on precise and dynamic regulation of gene expression, much of which is controlled by Regulatory networks and hub genes governing spermatogonial st...
Spermatogenesis—the process of sperm cell development—is highly dependent on precise and dynamic regulation of gene expression, much of which is controlled by Regulatory networks and hub genes governing spermatogonial stem cells (SSC) identity, including components involved in post-transcriptional regulations. During this complex process, a wide range of RNA-binding proteins (RBPs) and RNA processing enzymes coordinate the transcription, splicing, transport, storage, and translation of mRNAs required for germ cell development. Raw sequencing data were processed and normalized using standard bioinformatics pipelines (e.g., STAR, DESeq2). To identify key Regulatory networks and hub genes governing SSC identity, including components involved in post-transcriptional regulations, we applied integrative omics approaches by combining transcriptomic data with publicly available proteomic and interactome databases. Hub proteins were determined through weighted gene co-expression network analysis (WGCNA) and centrality scoring in protein-protein interaction (PPI) networks. Machine learning models, including random forest and support vector machine (SVM), were trained to classify critical regulators based on expression features and metadata. Additionally, cell-cell communication was inferred using ligand-receptor interaction analysis via CellChat and NicheNet to explore the microenvironmental impact on RNA metabolic processes. All findings were validated across culture conditions and biological replicates to ensure robustness. Microarray analysis revealed 92 upregulated and 126 downregulated genes in SSCs versus htFib, with enrichment in motile cilium assembly, spermatid development, and gamete generation. DEGs were mainly extracellular matrix proteins, transporters, and adhesion molecules. PPI network and KEGG analyses identified key hub genes (e.g., MMP3, CAV1, TGFBR2) involved in cell cycle and meiosis pathways. Single-cell RNA-seq of human testicular cells identified 17 clusters, including germ and somatic cell types. Germ cell re-clustering defined SSC subpopulations marked by genes such as FAM74F1, SMCP, and ADAD1. GSEA indicated metabolic shifts, especially in oxidative phosphorylation, during SSC differentiation. Ligand–receptor analysis revealed active cell-cell signaling, particularly involving fibroblasts and macrophages. These findings enhance the understanding of human spermatogonia culture and gene expression, providing insights into SSC biology and potential applications in reproductive medicine.
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