Infectious Agents and Cancer最新文献

{"title":"SOX9 and TNFAIP3 dysregulation in HCV-associated HCC after DAA therapy: insights into post-viral oncogenic memory.","authors":"Rehab I Moustafa, Sally Farouk, Hassan Elsayed, Hend I Shousha, Maha M Elbrashy, Ahmed M Gabr, Ahmed A Yousif, Ahmed Ramadan, Ayman Yosry, Ashraf O Abdelaziz, Amr Abdelaal, Noha G Bader El Din","doi":"10.1186/s13027-026-00735-w","DOIUrl":"10.1186/s13027-026-00735-w","url":null,"abstract":"<p><strong>Background: </strong>Hepatitis C virus (HCV) is a leading cause of chronic liver disease and hepatocellular carcinoma (HCC). Despite the high efficacy of direct-acting antivirals (DAAs) in eradicating HCV, HCC may still develop after sustained virological response (SVR), suggesting that HCV may leave behind lasting epigenetic and immunological alterations that sustain oncogenic risk.</p><p><strong>Objectives: </strong>This study aimed to investigate the expression profiles of SOX9, TNFAIP3, and FOSL2 in peripheral blood mononuclear cells (PBMCs) and liver tissues from HCV-related HCC patients and to explore, through in silico analyses, their molecular and immunological roles in HCV-driven hepatocarcinogenesis.</p><p><strong>Methodology: </strong>Gene expression was quantified in PBMCs and liver tissues using RT-qPCR. Receiver operating characteristic (ROC) curve analyses assessed diagnostic potential. In silico analyses evaluated protein-protein interactions, gene-gene networks, epigenetic modifications, and correlations with immune cell infiltration and immunomodulatory molecules using publicly available datasets.</p><p><strong>Results: </strong>SOX9, TNFAIP3, and FOSL2 were identified as interconnected regulators within NF-κB and TGF-β pathways, enriched in inflammatory and infection-related processes, and epigenetically modulated via promoter hypermethylation and histone remodeling. Their expression strongly correlated with macrophages, T cells, dendritic cells, and key immune modulators. RT-qPCR validation confirmed overexpression of SOX9 and TNFAIP3 in PBMCs and liver tissues from HCV-HCC patients, with PBMC levels closely reflecting tissue expression, and ROC analyses highlighted their potential as non-invasive biomarkers.</p><p><strong>Conclusions: </strong>SOX9 and TNFAIP3 emerge as key mediators linking persistent epigenetic alterations with immune remodeling in HCV-related HCC, and as potential non-invasive biomarkers for evaluation of HCC risk and post-DAA surveillance.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13020310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Digital health technologies in medicine: evidence, artificial intelligence integration, and ethical challenges.","authors":"Marco Cascella, Cesare Pane, Marcello Di Pumpo, Enrico Sebastiani, Martino Bussa, Alessio Tagliaferri, Barbara Brunetti, Pierluigi Meloni, Elisa Bianchini, Paolo Graziani, Federico Faustini, Guido D'Onofrio, David Manetta, Cristina Angela Catania, Chiara Jole Fornari, Andrea Scarda, Federica Smanio, Cristina Imbesi, Maria Teresa Avella, Roberta Fusco, Vincenza Granata","doi":"10.1186/s13027-026-00737-8","DOIUrl":"10.1186/s13027-026-00737-8","url":null,"abstract":"<p><p>Digital health technologies (DHTs), including digital therapeutics (DTx), are revolutionizing patient care by enabling the prevention, management, and treatment of medical conditions. These tools comprise care delivery mobile applications, wearable devices, and cloud platforms for capturing real-time data and enabling remote monitoring. DTx are regulated, software-based interventions that deliver evidence-supported therapeutic effects; artificial intelligence (AI) and machine learning, including advanced architectures, such as agentic systems and digital twins, may augment DTx workflows but are not defining features of DTx. Growing evidence supports the effectiveness of DHT strategies across different clinical fields. For example, wearable and remote patient monitoring technologies enable continuous assessment and personalized feedback in cardiology and neurology. Additionally, AI-enabled devices are widely implemented for continuous monitoring of glucose levels. However, several key challenges remain. Persistent gender and social biases in datasets and algorithms raise ethical concerns, particularly for underrepresented groups and pediatric populations. Mitigation strategies include regulatory frameworks, explainable AI, and trustworthy AI ecosystems. This work is a narrative, expert-driven review based on illustrative literature curated by domain specialists. It aims to synthesize current evidence, highlight implementation barriers, and propose recommendations to enhance inclusivity, interoperability, and real-world evaluation of digital health technologies. Applications of DHTs in animals within a One Digital Health framework, as well as potential applications in infection-related oncology, are also discussed.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12990400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota and glioblastoma: composition, mechanisms, and therapeutic interventions.","authors":"Setareh Nejadrostam, Pardis Shadvar, Seyed Behnamedin Jameie, Melika Jameie, Mona Farhadi","doi":"10.1186/s13027-026-00740-z","DOIUrl":"10.1186/s13027-026-00740-z","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor, associated with an exceedingly poor prognosis. The gut microbiota, a complex community of microorganisms, critically regulates host physiological homeostasis and communicates bidirectionally with the central nervous system via the gut-brain axis. Emerging evidence suggests that dysbiosis within this axis may profoundly influence GBM pathophysiology through inflammatory and immune-modulatory mechanisms, but a comprehensive synthesis of this complex interplay and its clinical implications remains vital for therapeutic advancement.</p><p><strong>Main body: </strong>This narrative review systematically synthesizes the existing literature from MEDLINE (via PubMed), Scopus, and Web of Science, covering publications up to September 26, 2025, to elucidate the multifaceted role of the gut microbiota-brain axis in GBM. Our study focuses on three critical domains: microbial composition alterations, mechanistic insights, and therapeutic interventions. The review confirms significant alterations in the gut microbial community in GBM across both clinical and preclinical models, with consistent enrichment or depletion of specific bacterial taxa that may affect tumor pathogenesis and prognosis. Mechanistically, gut microbiota-derived metabolites and receptor interactions are shown to modulate GBM progression by influencing tumor-promoting hallmarks, including metabolic reprogramming, immune evasion, and sustained proliferative signaling. Furthermore, the efficacy of standard treatments, including temozolomide chemotherapy and immune checkpoint inhibitors, is actively modulated by the patient's gut microbiota composition. Dietary approaches and traditional medicines further demonstrate microbiota-dependent effects on tumor progression and immune regulation.</p><p><strong>Conclusion: </strong>This review underscores the critical and intricate role of the gut microbiota-brain axis in GBM biology, affecting both tumor progression and therapeutic responsiveness. The compiled evidence establishes a clear rationale for advancing microbiota-targeted strategies as novel adjunctive interventions to enhance clinical outcomes for individuals with GBM.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13014736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of death-ligand-induced apoptosis in Epstein-Barr virus-encoded small RNAs-expressing human T-cell line.","authors":"Yuki Matsumoto, Ayako Tateishi, Hiroyuki Kanno","doi":"10.1186/s13027-026-00736-9","DOIUrl":"10.1186/s13027-026-00736-9","url":null,"abstract":"<p><p>BACKGROUND: In chronic active Epstein-Barr virus (EBV) (CAEBV) disease, EBV infects T or natural killer (NK) cells, and patients frequently exhibit a broad spectrum of EBV-associated T/NK-cell lymphoproliferative disorders including polyclonal, oligoclonal, and monoclonal proliferation, and sometimes develop EBV-positive NK/T-cell lymphoma. In the development of malignant tumor, the acquisition of the ability of resisting cell death is an important factor. METHODS: We have introduced a plasmid containing the coding sequences of EBV-encoded small RNAs (EBERs) or latent membrane protein (LMP) 1 into human T-lymphocyte virus-I-negative human T-cell lines using an expression plasmid vector harboring EBV nuclear antigen 1 and established stable transformants. Using these stable transformants, we evaluated the change of sensitivity to apoptosis induction with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo2L or soluble FasL (sFasL) in T cell lines with the expression of latent EBV genes, EBERs or LMP1. RESULTS: Among five human T-cell lines examined, Jurkat was the most sensitive cell line to the induction of cell death with both of Apo2L and sFasL, and the stable transformants of Jurkat cells expressing EBERs (Jurkat/E6) or LMP1 (Jurkat/L) exhibited the resistance to the cell death induced with both of Apo2L and sFasL. In Jurkat/E6 cells, the expression of cFLIPS, which blocks procaspase-8 activation and apoptosis, was a little enhanced, and in Jurkat/L cells, the phosphorylation of IκBα was constitutively upregulated, which leads to cell survival signals. Furthermore, Jurkat/E6 cells with decrease expression of EBERs after 6-months-culture without plasmid selection antibiotics exhibited the restored sensitivity to both death ligands-induced apoptosis in part, although Jurkat/L cells with decreased expression of LMP1 did not. CONCLUSION: EBERs would be responsible for the induction of resistance to death-ligand-induced apoptosis, and might contribute to the development of EBV-positive lymphoma of non-B-cell lineage. </p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12997878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Illuminating the pathological, immunohistochemical, and molecular investigations of myelocytomatosis in chicken embryos.","authors":"Ahmed Fotouh, Ahmed K Elsayed, Ali Mahmood Zanaty, Said Elshafae, Eman Abd El-Menamm Shosha","doi":"10.1186/s13027-026-00731-0","DOIUrl":"10.1186/s13027-026-00731-0","url":null,"abstract":"<p><p>Avian leukosis virus Subgroup-J (ALV-J) is an avian retrovirus affecting a wide range of avian species, and has posed a great threat to the local poultry with significant losses. In Egypt, ALV-J has been actively monitored in various breeder flocks. This study investigated 200 eggs from ALV-J positive breeders, confirmed positive-polymerase chain reaction (PCR)-ALV-J, collected from a hatchery between January 2022 and December 2023. 200 tissue specimens (liver, heart, spleen, kidney, and lung) were collected from suspected embryos for PCR test, immunopathological identification, and sequencing analysis. To the best of our understanding, this is the first study specifically detecting ALV-J infection in chicken embryos in Egypt. The current study focuses on the genetic evolution and sequencing analysis of ALV-J isolates from chicken embryos across three Egyptian governorates: El-Sharkia, Al-Qalyubiya, and New Valley. Postmortem findings of the infected embryos showed stunting, curling, dwarfing, hemorrhagic body surface, enlarged liver, and congestion of chorio-allantoic membranes (CAM). Histopathological observation demonstrated no lymphoid or myeloid cell infiltrations, only degenerative changes and congestion of the examined organs existed. The immunohistochemical staining confirmed that the viral-positive signals were visceral tissues as the spleen, liver, and kidney. Only 30 samples were PCR-positive for ALV-J gp85 gene at size of 545 base pairs with a prevalence rate of 15%. Two ALV-J positive samples were sequenced and deposited in the Genbank under accession numbers (PQ119499 - PQ119500, ALV-J-II). ALV-J-gp85 gene phylogeny showed that the AlQalyubiya-1-EGYALVJ-env isolate is highly genetically correlated to Chinese strains (KJ179914-ALV-J-GD27, KJ179912-ALV-J-GD19, KJ179911-ALV-J-GD31) with nucleotide and amino acid identities of 98-100%; respectively. Moreover, Newvalley-2-EGYALVJ-env isolate is close similar to previous mentioned Chinese strains with nucleotide identity percentages of 98% and amino acid identity percentage 97%, 96%, 96%; respectively. This study confirmed that our two ALV-J isolates are not completely similar to the current Egyptian isolates. Also, ALV-J infection was continuously distributed in the breeders and considered one of the factors contributing to the tumor epidemics.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12955225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silencing HPV: the rise of RNA therapeutics in cervical cancer.","authors":"Samira Mohammadi Khorramabadi, Nader Ebrahimi, Parisa Shiri Aghbash, Zahra Zenderuh Ravanlo, Hossein Bannazadeh Baghi","doi":"10.1186/s13027-026-00733-y","DOIUrl":"10.1186/s13027-026-00733-y","url":null,"abstract":"<p><p>Despite the availability of preventative HPV vaccinations, cervical cancer remains a worldwide health concern. It is mostly caused by persistent infection with high-risk human papillomaviruses. Therapeutic techniques targeting the viral oncogenes E6 and E7, which are constitutively expressed in HPV-positive cervical cancers and inactivate the important tumor suppressors, p53 and Rb, offer intriguing molecular treatment options. RNA-based techniques, such as tiny interfering RNA, short hairpin RNA, antisense oligonucleotides, and mRNA-based vaccines for the selective silencing of E6/E7 genes, have emerged as leaders in targeted therapeutics. Preclinical studies have shown that RNA-mediated suppression of E6/E7 can restore p53 and Rb activity, causing apoptosis or senescence in cervical cancer cells and inhibiting tumor growth in animal models. Similarly, mRNA vaccination platforms encoding E6/E7 have been found to potently induce HPV T-cell responses and full tumor regression in animal models. RNA-based therapeutics in patients are now being evaluated in early-stage clinical studies, including novel mRNA vaccines for HPV-positive malignancies in combination with immunotherapies. While no RNA-based treatment for cervical cancer has yet achieved regulatory approval, this review summarizes the significant progress in this field that has been effective in therapies for cervical cancer using new strategies, such as advanced delivery systems, combinatorial treatments, and genome editing strategies.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":" ","pages":"18"},"PeriodicalIF":2.8,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12896261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146085733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generalized structural equation modeling of demographic disparities in human papillomavirus (HPV) vaccine uptake among female schoolteachers in a middle eastern country.","authors":"Saeed Akhtar, Juman Rezqalla, Mariam Alshatti, Amna Ibraheem, Danah Omar, Houda Al-Failakawi, Shamayel AlHaqqan, Sarah AlGhurair","doi":"10.1186/s13027-025-00728-1","DOIUrl":"10.1186/s13027-025-00728-1","url":null,"abstract":"<p><p>BACKGROUND: The complex mechanisms involving knowledge and behavioural factors in causing low human papillomavirus (HPV) vaccine uptake are not yet fully understood. This study sought to disentangle direct, indirect, and total effects (DE, IDE, TE) of age, unawareness of HPV causal role in cervical cancer and family history of cervical cancer on HPV vaccine uptake among females. METHODS: In a cross-sectional study, female schoolteachers employed in public and private-sector high schools were enrolled. Data were collected using a self-administered questionnaire during January 2018. Prevalence of HPV vaccine uptake was computed. The effects of age, and family history of cervical cancer through mediator (i.e. unawareness of HPV's causal role in cervical cancer) on HPV vaccine uptake were examined in a generalized structural equation modeling (GSEM) framework. RESULTS: Of 1,341 participants, 60% were unaware of HPV causal role in cervical cancer and 98.1% were HPV unvaccinated. The results of GSEM showed that participants had significantly higher odds of being unvaccinated if they were unaware of the causal role of HPV in cervical cancer (p = 0.001) or had no family history of cervical cancer (p < 0.001). Moreover, absence of a family history of cervical cancer had a significant (p = 0.020) indirect effect on HPV vaccine uptake. The proportion of indirect effect mediated was 61.61%. CONCLUSION: Increasing awareness about the HPV's causal role in cervical cancer, and benefits of HPV vaccine may augment the HPV vaccine uptake. If implemented, future studies may look at the impact of such efforts. </p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"21 1","pages":"6"},"PeriodicalIF":3.2,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12853900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146092958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial vaginosis in microscopic examination of Pap smears in patients with high-risk HPV is associated with viral persistence and cytological progression in a longitudinal study.","authors":"Lara Linz, Nina Zachau, Sibylle Spieth, Patrick Finzer","doi":"10.1186/s13027-026-00734-x","DOIUrl":"10.1186/s13027-026-00734-x","url":null,"abstract":"<p><p>BACKGROUND: The vaginal microbiome is increasingly studied using sequencing approaches; however, the exact bacterial community structure in vaginal diseases, e.g. bacterial vaginosis (BV), remains unclear. Vaginal Pap smears routinely obtained in preventive screening programs can also be evaluated with high accuracy regarding microbial colonization by means of microscopy. METHODS: This longitudinal retrospective case control study aims to investigate the relationship between microscopic vaginal flora observed in Pap-smears and Human Papilloma Virus (HPV) clearance, persistence or progression using HPV-PCR tests and the results of the Pap-smears. Two cohorts of high-risk HPV positive patients were formed. Cohort A (n = 136) was observed over a two-year time period 2020–2022, while cohort B (n = 160) was observed over a one-year period from 2021 to 2022. Each case group consisted of BV-positive patients that were compared to BV negative patients as controls. RESULTS: It was found that the case groups in both cohorts had a higher HPV persistence rate and a higher rate of progression at follow-up. Lactobacillus flora was consistently associated with favorable outcomes, particularly higher HPV clearance rates across both cohorts and the entire observation period. In contrast patients with bacterial vaginosis (BV) were associated with significantly increased risk of HPV progression, especially in Cohort B, supporting its role as risk factor in the development of precancerous cervical lesions. CONCLUSION: The integration of microscopic flora assessment into screening programs for cervical cancer may help to improve risk stratification in HPV positive women. Our findings suggest that, BV-positive patients may benefit from a closer follow-up period and earlier therapeutic intervention. CLINIAL TRIAL NUMBER: Not applicable. </p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":" ","pages":"16"},"PeriodicalIF":3.2,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12895659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146085687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel C-terminal HBx truncation (G135) in genotype D1 HBV: predicted effects on oncogenic signaling.","authors":"Kamyar Mazloum Jalali, Hamidreza Mollaei, Chiman Karami, Elahe Mosayebnejad Roudbaneh","doi":"10.1186/s13027-026-00730-1","DOIUrl":"10.1186/s13027-026-00730-1","url":null,"abstract":"<p><p>BACKGROUND & AIMS: Hepatitis B virus X protein (HBx) is a multifunctional viral regulator implicated in hepatocellular carcinoma (HCC). We aimed to characterize HBx mutations in liver tissue samples from Iranian patients with HCC and explore their potential structural and functional implications. METHODS: Liver tissue samples from 10 patients with HCC and chronic HBV infection were analyzed using high-resolution melting (HRM) and Sanger sequencing. Detected variants were assessed by phylogenetic analysis, 3D protein modeling, and STRING-based protein–protein interaction (PPI) mapping. Correlations with clinical and biochemical parameters were examined. RESULTS: Multiple HBx mutations were identified, including a novel nonsense mutation at codon 135 (G135*), resulting in C-terminal truncation. Additional substitutions were found in the H-box (V88A, K94E, A100T), BH3-like motif (L113P, Q116R, E122K, A126T), and CCCH zinc-binding domain (C61S, C69R). Structural modeling predicted that these variants may potentially disrupt DDB1 and Bcl-2 interactions, as well as zinc coordination. STRING analysis suggested altered HBx connectivity with TP53, BAX, TNF, IL6, and CREB1, potentially affecting apoptosis, transcriptional regulation, and inflammatory signaling. Phylogenetic analysis confirmed that variants clustered within genotype D1, indicating intra-genotypic adaptation. Clinically, higher viral loads and HBeAg positivity were associated with elevated liver injury markers, consistent with the predicted functional impacts of these variants. CONCLUSIONS: HBx mutations in genotype D1, particularly the novel C-terminal truncation, may potentially influence viral persistence, apoptotic resistance, and oncogenic signaling in HCC, pending experimental validation. These findings highlight intra-genotypic HBx diversity as a potential biomarker and therapeutic target for HBV-related liver cancer. CLINICAL TRIAL NUMBER: Not applicable. </p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"21 1","pages":"17"},"PeriodicalIF":3.2,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12895752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential expression and prognostic role of ACACA, ACLY, and FASN in schistosomiasis-associated versus hepatitis B virus-related liver cancer.","authors":"Xiao-Yi Wang, Yi-Hui Sun, Qiong-Le Wu, Man-Man Liang, Zi-Jian Wang, Yao Hao, Zhi-Yu Pan, Xiu-Liang Xu, Jiang-Hua Yang","doi":"10.1186/s13027-026-00732-z","DOIUrl":"10.1186/s13027-026-00732-z","url":null,"abstract":"<p><p>OBJECTIVE: To investigate the clinicopathological differences between schistosomiasis-related liver cancer (Sj-LC) and hepatitis B virus-related liver cancer (HBV-LC), as well as the expression and prognostic significance of key lipid metabolism enzymes (ACACA, ACLY, FASN). METHODS: A retrospective analysis was performed on 309 HBV-LC and 44 Sj-LC patients treated at the First Affiliated Hospital of Wannan Medical College from June 2016 to December 2024. AJCC staging was conducted for 183 HBV-LC and 25 Sj-LC cases (June 2016–June 2021). Transcriptome data of 111 HBV-LC cases were retrieved from the Cancer Genome Atlas (TCGA) database for analysis. Gender- and age-stratified tissue samples (Sj-LC, HBV-LC, and normal liver tissues) were subjected to immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (RT-qPCR) to detect the expression of ACACA, ACLY, and FASN. RESULTS: Compared with HBV-LC, Sj-LC had a lower male proportion (68.2% vs. 86.1%, P = 0.003), an older age at onset (66.38 ± 8.364 vs. 60.75 ± 11.682 years, P < 0.001), a lower proportion of hepatocellular carcinoma (P < 0.001), higher incidences of gastrointestinal bleeding, hepatic encephalopathy, metastasis, and extrahepatic spread (all P < 0.05), and a more advanced tumor stage (predominantly IVB, P < 0.001). Sj-LC also exhibited higher levels of D-dimer, cholesterol, and triglycerides (all P < 0.01). Bioinformatics analysis showed upregulated expression of ACACA, ACLY, and FASN in HBV-LC. IHC and RT-qPCR results confirmed higher expression of these enzymes in Sj-LC (larger positive areas, stronger staining intensity, and higher amplification folds), with ACLY expression significantly overexpressed compared to normal liver tissues. CONCLUSION: Sj-LC exhibits distinct clinicopathological features and lipid metabolism enzyme expression profiles compared with HBV-LC, characterized by older onset age, more complications, stronger invasiveness, and advanced stage at diagnosis. Elevated ACACA, ACLY, and FASN expression suggests that lipid metabolism reprogramming may be associated with the malignant phenotype of Sj-LC. Notably, these enzymes were not confirmed as independent prognostic factors for Sj-LC, and their direct association with prognosis requires further verification in expanded cohorts. Targeted individualized diagnosis, treatment, and early screening strategies are warranted for Sj-LC. </p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":" ","pages":"14"},"PeriodicalIF":3.2,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12874864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}