{"title":"Comprehensive Insights into APOBEC Mutations in Thyroid Cancer: Prognostic and Therapeutic Discoveries.","authors":"Wei Luo, Feng Liu, Mengyu Li, Jialong Yu, Ziyun Liu, Xuan Cheng, Yue Huang, Yu Liu, Mei Tao, Yuqi Wang, Yiping Zou, Xiaobin Shang, Chao Yang, Xianhui Ruan, Yanchao Qin, Xiangqian Zheng","doi":"10.1186/s12575-025-00288-z","DOIUrl":"https://doi.org/10.1186/s12575-025-00288-z","url":null,"abstract":"<p><strong>Background: </strong>The APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) family plays a vital mutagenic role in diverse human malignancies. Nevertheless, the biological characteristics of APOBEC family members and their clinical significance in cancer have not been comprehensively explored. Our primary objective was to characterize the distribution and clinical relevance of APOBEC family members and their mutations across multiple cancer types, with a particular focus on thyroid carcinoma (THCA).</p><p><strong>Methods: </strong>In this study, we employed an integrated, multi-faceted approach combining diverse statistical and bioinformatics methods. Data sources included whole-exome sequencing (WES), targeted next-generation sequencing (NGS), bulk RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), Western blot assays, drug sensitivity analyses, and in vivo animal models.</p><p><strong>Results: </strong>APOBEC mutations occupy a significant position in the mutation landscape of THCA. High APOBEC mutation enrichment scores were strongly associated with poor prognosis, immune evasion, and increased risk of malignant progression in THCA patients. These mutations contribute to tumor advancement and influence cellular differentiation within the tumor microenvironment. Additionally, we developed a prognostic APOBEC mutagenesis model using machine learning, which was validated across multiple THCA cohorts. In vitro and in vivo experiments demonstrated that APOBEC2 inhibition effectively suppressed tumor proliferation, metastasis, and glycolytic activity, while simultaneously enhancing immune activation and boosting the efficacy of immune checkpoint inhibitors.</p><p><strong>Conclusion: </strong>Our study systematically characterizes APOBEC mutations across various cancer types and underscores their promise as biomarkers for aggressive tumor phenotypes, prognostic assessment, and immunotherapy response to THCA. These findings were accomplished through multi-omics sequencing and validated through comprehensive in vitro and in vivo experiments.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"28"},"PeriodicalIF":3.7,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuan Hepei, Zeng Jun, Khan Muhammad, Wang Baiyao, Hu Xiaoshan, Wei Hao, Wang Zhaotong, Yuan Yawei
{"title":"FNDC5 and ACOX1 as Biomarkers of Peroxisomal Activity with Contrast Outcomes in Colon Adenocarcinoma.","authors":"Yuan Hepei, Zeng Jun, Khan Muhammad, Wang Baiyao, Hu Xiaoshan, Wei Hao, Wang Zhaotong, Yuan Yawei","doi":"10.1186/s12575-025-00289-y","DOIUrl":"https://doi.org/10.1186/s12575-025-00289-y","url":null,"abstract":"","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"27"},"PeriodicalIF":3.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immunosenescence-Related Gene MAFF is Involved in Immune Regulation and Malignant Progression in Pancreatic Adenocarcinoma.","authors":"Fenglin Zhang, Kexin Liu, Mengfan Ao, Jiangang Zhao, Xinghe Liao, Ping Li, Hao Chen","doi":"10.1186/s12575-025-00278-1","DOIUrl":"10.1186/s12575-025-00278-1","url":null,"abstract":"<p><p>Immunosenescence has lately become a focal point in oncology investigations. Nevertheless, its significance in pancreatic adenocarcinoma (PAAD) remains to be elucidated. This research sought to examine the predictive value and treatment implications of immunosenescence-related genes in PAAD. We use the public datasets from TCGA and GEO to extract clinicopathological factors and RNA-sequencing data. Differentially expressed genes (DEGs) were ascertained, and then molecular subtypes were classified by consensus clustering. Functional enrichment analysis using KEGG and GO, GSEA, survival analysis, and the design of an immunosenescence-linked risk signature using Lasso-Cox regression is part of the analytical approach. We used TIMER, TISCH, etc., to further elaborate its relationship with the tumor immune microenvironment. Drug sensitivity analysis is conducted using GSCA. The independent prognostic gene MAFF's expression was validated utilizing GEPIA2, real-time quantitative PCR (RT-qPCR), and western blot (WB). We identify two immunosenescence-associated subtypes of PAADwith distinct gene expression profiles and clinical outcomes. The creation of a risk signature model utilizing IMSRGs reveals three genes-NCAM1, SESN1, and MAFF-that are significantly correlated with overall survival. The elevated-risk cohort, as identified by the risk assessment metric, correlates with poorer survival rates. Additionally, we uncover an association between the risk indicator and the tumor milieu, encompassing immune cell infiltration patterns and drug sensitivity profiles. Our results and published data show that MAFF levels in pancreatic cancer tissues markedly exceeds that of normal tissues and have a bad effect on prognosis. The study identifies a prognostic gene signature for PAAD, revealing its potential in personalized medicine and immunotherapy, and highlights the role of immunosenescence in cancer treatment.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"26"},"PeriodicalIF":3.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoyu Yang, Bin Luo, Jianhui Tian, Yanhong Wang, Xinyi Lu, Jian Ni, Yun Yang, Lei Jiang, Shengxiang Ren
{"title":"Biomarkers and ImmuneScores in lung cancer: predictive insights for immunotherapy and combination treatment strategies.","authors":"Xiaoyu Yang, Bin Luo, Jianhui Tian, Yanhong Wang, Xinyi Lu, Jian Ni, Yun Yang, Lei Jiang, Shengxiang Ren","doi":"10.1186/s12575-025-00287-0","DOIUrl":"10.1186/s12575-025-00287-0","url":null,"abstract":"<p><p>Lung cancer remains the leading cause of cancer related deaths worldwide. Immunotherapy and combination therapies, involving chemotherapy, radiotherapy, and tumor anti-angiogenesis therapy, have shown promising clinical results and are expected to become a key approach in the future management of lung cancer. However, due to immune resistance, immunotherapy remains highly effective in only a subset of patients, while many others either do not respond initially or develop resistance over time. Moreover, immune-related adverse events induced by immunotherapy, further complicate treatment outcomes and prognosis. Immune-related biomarkers and ImmuneScores have driven the development of personalized immunotherapy strategies for lung cancer, and they can aid in predicting immune resistance, and forecasting immune-related adverse events (irAEs). This review summarizes the prognosis value of immune-related biomarkers and ImmuneScores in immunotherapy and combination therapies for lung cancer. The aim is to provide a foundation for personalized treatment and management of lung cancer, while offering guidance for future research directions in immunotherapy.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"25"},"PeriodicalIF":3.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12243280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yao Liu, Zujun Que, Tianqi An, Zhipeng Zhang, Jianhui Tian
{"title":"Mitigating Tumor Recurrence through Mitochondrial Metabolism Inhibition: A Novel NIR Laser-Induced Therapeutic Strategy.","authors":"Yao Liu, Zujun Que, Tianqi An, Zhipeng Zhang, Jianhui Tian","doi":"10.1186/s12575-025-00283-4","DOIUrl":"10.1186/s12575-025-00283-4","url":null,"abstract":"<p><p>Tumor recurrence driven by mitochondrial hypermetabolism remains a critical challenge in cancer therapy, as aberrant energy metabolism fuels therapeutic resistance and disease progression. We aimed to develop a multifunctional nanoplatform combining mitochondrial metabolism inhibition, photothermal therapy, and controlled chemotherapy to overcome tumor recurrence mechanisms. Biodegradable polydopamine nanoparticles (PDA-DOX-CO NPs) were engineered via molecular self-assembly, co-loading doxorubicin (DOX) and a carbon monoxide (CO) prodrug. The PDA-DOX-CO NPs demonstrated three synergistic therapeutic effects: (1) Photothermal ablation (48.38 °C tumor hyperthermia), (2) CO-mediated mitochondrial suppression, and (3) Spatiotemporally controlled DOX release. In HCT-116 tumor models, PDA-DOX-CO NPs with NIR irradiation induced 60% tumor complete ablation. Histopathological analysis confirmed significant apoptosis induction and mitochondrial morphology alterations in treated tumors. This \"metabolic blockade + energy depletion + precision delivery\" paradigm provides a synergistic solution to tumor recurrence, demonstrating enhanced therapeutic efficacy and biosafety through mitochondrial-targeted multimodal action.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"24"},"PeriodicalIF":3.7,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12219048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Photothermal Hyperthermia Suppresses Liver Tumor Growth Via Hippo Signaling Pathway-Dependent Inhibition of Cell Proliferation and Induction of Apoptosis.","authors":"Jian Li, Yuanhua Qin, Yingying Yang, Hang Chen, Mengjuan Li, Yadi Liu, Bingjie Liu, Jingli Shang, Yu Zhang, Tao Han, Yuhan Hu, Feng Ren","doi":"10.1186/s12575-025-00282-5","DOIUrl":"10.1186/s12575-025-00282-5","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) ranks as the third most common malignant tumor globally. Although hyperthermia has shown promise as a non-invasive treatment for tumors, its specific mechanisms and impact on HCC remain underexplored. This study aims to investigate the effects of hyperthermia on HCC proliferation and apoptosis and to elucidate the role of the Hippo signaling pathway in these processes. Huh7 and HepG2 HCC cells were cultured at various temperatures (37 °C, 40 °C, 43 °C, and 46 °C), with 37 °C as the control. Cell proliferation, apoptosis, and cell cycle distribution were assessed via CCK-8 assays and flow cytometry. A subcutaneous xenograft model in nude mice, treated with indocyanine green (ICG) and near-infrared (NIR) irradiation to achieve local hyperthermia, was used to evaluate in vivo tumor growth. RNA-seq and KEGG pathway analyses identified differentially expressed genes, and Western blotting and immunofluorescence were used to confirm the involvement of the Hippo signaling pathway. Hyperthermia at 43 °C significantly inhibited Huh7 and HepG2 cell proliferation and induced apoptosis, accompanied by cell cycle arrest. In vivo, local hyperthermia reduced tumor volume and weight in the ICG + NIR-treated group. RNA-seq and KEGG analyses revealed that the Hippo signaling pathway was activated under hyperthermic conditions, with YAP expression and nuclear translocation markedly downregulated. Further experiments showed that YAP overexpression mitigated hyperthermia-induced effects on cell proliferation and apoptosis, underscoring the role of the Hippo pathway. These findings demonstrate that hyperthermia inhibits HCC growth by regulating the Hippo signaling pathway, reducing cell proliferation, and promoting apoptosis. This study highlights the potential of hyperthermia as an effective therapeutic approach for HCC, with implications for developing targeted hyperthermic therapies.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"22"},"PeriodicalIF":3.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Establishment of a mouse lung cancer organoid model and its applications for therapeutic screening.","authors":"Yajing Liu, Jingyuan Ning, Donglai Wang","doi":"10.1186/s12575-025-00284-3","DOIUrl":"10.1186/s12575-025-00284-3","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer exhibits a high degree of heterogeneity, rendering its treatment one of the most difficult challenges. Current laboratory lung cancer models cannot fully preserve the diversity of the disease and predict drug responses. Owing to the rarity of human-derived samples, transgenic mouse models can be extensively used in fundamental research.</p><p><strong>Results: </strong>We established a mouse lung cancer organoid (LCO) model derived from a genetically engineered mouse model that can spontaneously develop lung cancer. Morphological and molecular assays demonstrated that the lung cancer organoids retained the histological architecture and stem-like characteristics of their parental tumors. Successfully constructed lung cancer organoids were amenable for high-throughput drug screening in vitro.</p><p><strong>Conclusions: </strong>This method can be used for the construction and identification of mouse-derived lung cancer organoids, which can be used to further comprehend the pathophysiology of lung cancer and evaluate drug responses in personalized medicine.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"21"},"PeriodicalIF":3.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rafid Jihad Albadr, Hayder Naji Sameer, Zainab H Athab, Mohaned Adil, Ahmed Yaseen, Omer Qutaiba B Allela
{"title":"Recent Advances in mRNA-Based Vaccines Against Several Hepatitis Viruses.","authors":"Rafid Jihad Albadr, Hayder Naji Sameer, Zainab H Athab, Mohaned Adil, Ahmed Yaseen, Omer Qutaiba B Allela","doi":"10.1186/s12575-025-00269-2","DOIUrl":"10.1186/s12575-025-00269-2","url":null,"abstract":"<p><p>Viral hepatitis is a significant danger to global public health as it is the primary cause of mortality worldwide. Hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV) are well-established infectious agents that significantly contribute to the development and transmission of hepatocellular carcinoma (HCC). Hepatitis E virus (HEV) is the pathogen responsible for acute viral hepatitis. 80% of liver malignancies are HCC, with HBV and HCV infections being the primary cause of seventy to eighty% of HCC cases. HEV may exacerbate liver inflammation and make other infections more severe. New vaccinations against the hepatitis virus are being developed to reduce the required doses for inducing an effective immune response and to help establish long-term protection in populations hyporesponsive to the vaccine. RNA-based vaccinations have emerged as a viable alternative. mRNA vaccines can help bridge the gap between the availability of effective vaccines and the rise of pandemic infectious diseases. Both human and animal studies have demonstrated that these vaccinations induce long-lasting and safe immunological responses. This review highlights the challenges faced in developing vaccines for the hepatitis virus, explicitly focusing on different vaccine candidates aimed at preventing or mitigating the illness. Here, we review the progress and comprehensive assessments of an mRNA-based vaccine designed to combat HAV, HBV, HCV, HDC, and HEV.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"20"},"PeriodicalIF":3.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanisms of drug resistance in hepatocellular carcinoma.","authors":"Yongchun Zou, Xinliang Wan, Qichun Zhou, Gangxing Zhu, Shanshan Lin, Qing Tang, Xiaobing Yang, Sumei Wang","doi":"10.1186/s12575-025-00281-6","DOIUrl":"10.1186/s12575-025-00281-6","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer, associated with high morbidity and mortality worldwide. Despite advancements in diagnostic methods and systemic treatments, including tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), the development of drug resistance remains a significant challenge in HCC management. Traditional treatments such as surgical resection and transarterial chemoembolization offer limited efficacy, especially in advanced stages. Although novel therapies like lenvatinib, sorafenib, regorafenib, and ICIs have shown promise, their effectiveness is often hindered by primary and acquired resistance, leading to poor long-term survival outcomes. This review focuses on the molecular mechanisms underlying resistance to targeted therapies and immunotherapies in HCC. Key factors contributing to resistance include alterations in the tumor microenvironment (TME), immune evasion, hypoxia, changes in cellular metabolism, and genetic mutations. Additionally, molecular players such as ferroptosis, autophagy, apoptosis, endoplasmic reticulum stress, ABC transporters, and non-coding RNAs(ncRNAs) are discussed as contributors to drug resistance. Understanding these mechanisms is critical for the development of novel therapeutic strategies aimed at overcoming resistance, improving patient outcomes, and ultimately enhancing survival rates in HCC patients.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"19"},"PeriodicalIF":3.7,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}