Zi-Han Qiu, Zhou Huang, Dong-Xing Shen, Li Zhu, Xiao-Bo Huang, Wei-Hu Wang, Jian Tie, Liang-Fang Shen, Mei Shi, Jia-Yi Chen, Min Liu, Jing Cheng, Jun Zhang, Hui Fang, Hao Jing, Yong-Wen Song, Jing Jin, Yue-Ping Liu, Bo Chen, Yuan Tang, Shu-Nan Qi, Ning-Ning Lu, Yi-Rui Zhai, Wen-Wen Zhang, Xin Liu, Ye-Xiong Li, Yu Tang, Shu-Lian Wang
{"title":"A nomogram to predict pathological axillary lymph node status in neoadjuvant chemotherapy-treated patients with breast cancer.","authors":"Zi-Han Qiu, Zhou Huang, Dong-Xing Shen, Li Zhu, Xiao-Bo Huang, Wei-Hu Wang, Jian Tie, Liang-Fang Shen, Mei Shi, Jia-Yi Chen, Min Liu, Jing Cheng, Jun Zhang, Hui Fang, Hao Jing, Yong-Wen Song, Jing Jin, Yue-Ping Liu, Bo Chen, Yuan Tang, Shu-Nan Qi, Ning-Ning Lu, Yi-Rui Zhai, Wen-Wen Zhang, Xin Liu, Ye-Xiong Li, Yu Tang, Shu-Lian Wang","doi":"10.1007/s12672-026-05558-0","DOIUrl":"https://doi.org/10.1007/s12672-026-05558-0","url":null,"abstract":"<p><strong>Objectives: </strong>Accurately predicting axillary pathological complete response (ypN0) after neoadjuvant chemotherapy (NACT) is of vital importance for making decisions regarding the axillary treatment plan for breast cancer patients. This study aimed to identify factors influencing ypN0 and to develop a predictive nomogram to evaluate the probability of ypN0 in NACT-treated patients with breast cancer.</p><p><strong>Methods: </strong>Overall, 1559 patients with cT1-4N1-2M0 breast cancer who received NACT and mastectomy between 2000 and 2014 in 12 institutions in China were analyzed retrospectively. Patients treated in three cancer hospitals (training set, n = 1072) were used to construct a nomogram based on multivariate logistic regression analyses. The nomogram was validated by determining the area under the receiver operating characteristic curve (AUC) and calibration curve values in patients from nine other general hospitals (validation set, n = 487).</p><p><strong>Results: </strong>In the training and validation sets, 26.8% (287 of 1072) and 22.4% (109 of 487) patients, respectively, achieved ypN0. The nomogram incorporated seven predictive factors including clinical T and N stages, histological grade, lymphovascular invasion, molecular subtype, NACT cycles, and clinical response to NACT. The AUC values for the training and validation sets were 0.748 (95% CI, 0.714-0.782) and 0.739 (95% CI, 0.684-0.794), respectively. In addition, the calibration curve showed good agreement between the nomogram-based predictions and the actual observations.</p><p><strong>Conclusion: </strong>A nomogram was established to predict the status of axillary lymph nodes in NACT-treated patients with breast cancer. The predictive model performed well both in the training and external validation sets. This nomogram can serve as a preoperative, non-invasive decision-support tool to assist clinicians in identifying candidates for axillary de-escalation strategies.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Applications of circulating tumor cells in esophageal cancer detection and treatment.","authors":"Fangyuan Long, Shungeng Zhang, Zongfu Dong, Xupeng Huang, Dingfei Li, Ronghang Hu","doi":"10.1007/s12672-026-05600-1","DOIUrl":"10.1007/s12672-026-05600-1","url":null,"abstract":"<p><p>Esophageal cancer (EC) is highly invasive, recurrent, and metastatic, with high incidence and mortality rates, particularly in China, where it remains endemic. Although metastasis has traditionally been considered a late event in tumor progression, increasing experimental and clinical evidence suggests that dissemination of tumor cells may occur at earlier disease stages than previously recognized [1]. Detection of circulating tumor cells (CTCs) in the bloodstream may indicate tumor dissemination, making CTCs a key factor in the metastatic cascade. In recent years, despite progress in CTC research, there is still a lack of systematic and significant evidence to confirm the diagnostic, monitoring, and prognostic value of CTCs in EC. This review aims to summarize current evidence on the relationship between CTCs and EC and to provide insights that may support improved management and treatment strategies for EC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integrative analysis of bulk and single-cell RNA sequencing reveals PHLDA3 as a key regulator of Hypoxic TAMs and prognostic biomarker in HNSC.","authors":"Jingxin Guo, Zifeng Cui, Jinhang Wang, Ran Sun","doi":"10.1007/s12672-026-05596-8","DOIUrl":"https://doi.org/10.1007/s12672-026-05596-8","url":null,"abstract":"<p><strong>Background: </strong>Head and neck squamous cell carcinoma (HNSC) is a highly aggressive malignancy characterized by a complex tumor microenvironment (TME). Despite advances in immunotherapy, the immunosuppressive microenvironment driven by metabolic reprogramming remains a critical factor contributing to treatment failure. The prognostic value of PHLDA3, a target gene of the p53 family, in HNSC and its specific mechanisms in shaping TME heterogeneity remain ill-defined.</p><p><strong>Methods: </strong>This study integrated large-scale transcriptomic data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, alongside single-cell RNA sequencing (scRNA-seq) data. A prognostic nomogram incorporating PHLDA3 and clinical characteristics was constructed using multivariate Cox regression analysis. Biological functions were assessed utilizing Weighted Gene Co-expression Network Analysis (WGCNA), Gene Set Variation Analysis (GSVA), and the drug sensitivity prediction algorithm, oncoPredict. At the single-cell resolution, algorithms including Seurat, CellChat, scMetabolism, and Monocle 2 were employed to comprehensively characterize cell type annotation, intercellular communication, metabolic activity scoring, and pseudotime differentiation trajectories.</p><p><strong>Results: </strong>PHLDA3 was significantly upregulated in HNSC tissues and strongly correlated with poor overall survival (OS). The PHLDA3-based nomogram demonstrated superior calibration and discrimination capabilities in both the training and validation cohorts. Genomic analysis revealed that high PHLDA3 expression was associated with a lower Tumor Mutation Burden (TMB) but an increased sensitivity to the PLK1 inhibitor, BI-2536. Single-cell analysis further unveiled that PHLDA3 expression was not ubiquitous; rather, it was specifically enriched in tumor-associated macrophage (TAM) subsets characterized by hypoxic and lipid metabolic signatures (Hypoxic TAMs and Lipid TAMs). These subpopulations exhibited transcriptomic signatures indicative of enhanced glycolysis and orchestrated immunosuppressive communication networks within the TME, predominantly via the SPP1-CD44 and MIF-CD74 signaling axes. Ultimately, through its specific enrichment in these metabolically reprogrammed TAM subsets, PHLDA3 intimately participates in remodeling an immunosuppressive TME, thereby facilitating tumor progression and immune evasion.</p><p><strong>Conclusions: </strong>PHLDA3 serves as a robust prognostic biomarker for HNSC. Its elevated expression is indicative not only of a low TMB status but also of a critical association with metabolically reprogrammed SPP1<sup>+</sup> TAM subpopulations. By potentially sustaining the survival and function of these specific TAMs under hypoxic conditions, PHLDA3 drives the formation of an immunosuppressive microenvironment, highlighting a promising therapeutic target for combined metabolic-immune strategies in HNSC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular mechanisms and adjuvant therapeutic potential of α-mangostin in cervical cancer.","authors":"Zheng Liu, Weilong Liu, Zhiqiang Liu","doi":"10.1007/s12672-026-05534-8","DOIUrl":"https://doi.org/10.1007/s12672-026-05534-8","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer remains a significant global health challenge for women. Conventional treatments, including surgery, radiotherapy, and chemotherapy, are frequently limited by side effects and the development of drug resistance.</p><p><strong>Objective: </strong>This review synthesizes the therapeutic potential of α-mangostin in cervical cancer, with particular emphasis on its anticancer properties and underlying molecular mechanisms.</p><p><strong>Methods: </strong>We searched Google Scholar, PubMed, Scopus, Web of Science Core Collection, and ScienceDirect for preclinical and clinical studies on α-mangostin in cervical cancer, and the retrieved evidence was critically evaluated and summarized narratively.</p><p><strong>Results: </strong>α-Mangostin exhibits multiple anticancer effects in cervical cancer. It induces apoptosis, suppresses proliferation, modulates key signaling pathways, downregulates the human papillomavirus (HPV) oncogenes E6 and E7, and reverses chemoresistance.</p><p><strong>Conclusions: </strong>Although these findings position α-mangostin as a promising adjuvant candidate for cervical cancer, the evidence remains preclinical. Dedicated clinical trials are needed before any therapeutic claim can be made, but continued investigation may ultimately help improve treatment outcomes and address the rising mortality associated with this disease.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bacteria mediated tumor therapy recent advances challenges and future perspectives.","authors":"Weihong Mao, Chunmin Deng","doi":"10.1007/s12672-026-05611-y","DOIUrl":"10.1007/s12672-026-05611-y","url":null,"abstract":"<p><p>Bacteria, as simple unicellular microorganisms, can directly lyse tumor cells following intratumoral administration. Flagellin and cell wall components derived from bacteria can reshape the tumor microenvironment and activate host anti-tumor immune responses. Notably, certain anaerobic and facultative anaerobic bacteria exhibits preferential colonization in the hypoxic core of solid tumors, where they can serve as in situ \"micro-bioreactors\" and targeted delivery vectors for synergistic tumor therapy. Based on rapid advances in synthetic biology, diverse engineered bacteria and bacteria-based biohybrid systems have been developed for precision tumor therapy, including gene restoration, environment-responsive programmable expression, cytotoxic protein production, and multimodal combination therapy with nanomaterials, immune modulators, or photothermal agents. These living platforms enable targeted drug/gene delivery, sustained local therapeutic output, and durable anti-tumor immune activation. However, clinical translation remains hindered by insufficient biosafety control, off-target colonization, uncontrolled proliferation, immune clearance, and lack of standardized manufacturing and regulatory guidelines. This review systematically summarizes the historical development, inherent anti-tumor mechanisms, genetic engineering strategies, and multimodal biohybrid systems of bacteria-mediated tumor therapy. We comprehensively discuss the advantages, limitations, comparative characteristics, and core bottlenecks of different platforms, and propose rational design strategies for next-generation intelligent, controllable, and clinically translatable bacteria-derived living anti-tumor systems.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13486457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An entosis-anchored hybrid prognostic signature identifies immunotherapy-resistant subgroups in head and neck squamous cell carcinoma.","authors":"Pan Xie, Ying Zhang, Zhichao Xiao, Mengting Tan, Zhikui Luo, Fusen Peng","doi":"10.1007/s12672-026-05567-z","DOIUrl":"https://doi.org/10.1007/s12672-026-05567-z","url":null,"abstract":"<p><strong>Background: </strong>Entosis is a non-apoptotic form of cell-in-cell death implicated in tumor progression and immune evasion. However, the prognostic and immunological significance of entosis-related genes in head and neck squamous cell carcinoma (HNSCC) has not been systematically studied. This study aimed to construct and validate an entosis-anchored hybrid prognostic signature for HNSCC and to characterize its association with the tumor immune microenvironment and therapeutic response.</p><p><strong>Methods: </strong>Gene expression and clinical data of 565 HNSCC patients from The Cancer Genome Atlas (TCGA) were used as the discovery cohort, randomly split into training (n = 396) and testing (n = 169) sets. A hybrid strategy integrating entosis pathway genes with genome-wide candidates was employed to construct a 14-gene prognostic signature via LASSO-Cox regression. External validation was performed in GSE65858, GSE41613, and CPTAC cohorts, with a fixed-effect meta-analysis synthesizing the results. Immune infiltration, immune checkpoint expression, TIDE-based immune evasion, drug sensitivity (oncoPredict/GDSC2 cell-line data), and a clinical nomogram were also evaluated.</p><p><strong>Results: </strong>The 14-gene entosis-anchored signature (ERS-14) comprised four entosis core genes (MYL2, CDKN2A, LAMP1, SPP1) and ten genome-wide prognostic genes. In the TCGA cohort, ERS-14 achieved a concordance index (C-index) of 0.703 and time-dependent AUC values of 0.737, 0.739, and 0.725 at 1, 3, and 5 years, respectively. Meta-analysis across external cohorts confirmed its prognostic value (HR = 1.551, 95% CI 1.147-2.096, p = 0.004, I² = 0%). Multivariate Cox regression demonstrated that ERS-14 was an independent predictor (HR = 4.362, p < 2 × 10⁻²⁰), and subgroup analysis revealed consistent prognostic performance across all 13 clinical subgroups tested. The high-risk group exhibited a T cell exclusion phenotype characterized by elevated cancer-associated fibroblast (CAF) scores (p = 0.008), downregulated immune checkpoints, and significantly increased resistance to cisplatin (p = 0.0001) and multiple targeted agents.</p><p><strong>Conclusions: </strong>We developed and validated ERS-14, an entosis-anchored hybrid prognostic signature in HNSCC that predicts survival, identifies an immunosuppressive microenvironment driven by T cell exclusion, and reveals therapeutic vulnerabilities that may inform treatment selection.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huanzhi Peng, Lili Tang, Kai Wang, Manyuan Li, Li Tang, Quanxing Liu
{"title":"A retrospective study on the rehabilitation effects of IMB nursing intervention for lung cancer patients after cryoablation.","authors":"Huanzhi Peng, Lili Tang, Kai Wang, Manyuan Li, Li Tang, Quanxing Liu","doi":"10.1007/s12672-026-05606-9","DOIUrl":"https://doi.org/10.1007/s12672-026-05606-9","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate whether an Information-Motivation-Behavioral Skills (IMB)-based perioperative nursing program was associated with better self-efficacy, quality of life, complication profiles, and nursing satisfaction in patients with lung cancer undergoing cryoablation.</p><p><strong>Methods: </strong>This single-center retrospective cohort study included 552 patients treated between July 2023 and March 2025. Patients received either IMB-based perioperative nursing (n = 268) or routine care (n = 284) according to routine clinical allocation rather than randomization. SUPPH and FACT-L scores were assessed at baseline and 3 months. Longitudinal changes were examined with repeated-measures models, and follow-up differences were further assessed with baseline-adjusted ANCOVA. Complications were compared with χ² or Fisher's exact tests and summarized with risk ratios (RRs) and 95% confidence intervals (CIs). Adjusted logistic models were used for any complication, pneumothorax, and pain. Nursing satisfaction was compared with mean difference, 95% CI, and Cohen's d.</p><p><strong>Results: </strong>Baseline scores were similar between groups. At 3 months, the intervention group had higher SUPPH scores than the control group (104.66 ± 6.09 vs. 86.43 ± 4.35); the group-by-time interaction was 18.09 (16.96 to 19.22) (P < 0.001) and the baseline-adjusted mean difference was 18.23 (17.35 to 19.11) (P < 0.001). FACT-L scores also favored the intervention group (101.90 ± 12.72 vs. 94.57 ± 9.98), with a group-by-time interaction of 6.97 (4.93 to 9.01) (P < 0.001) and a baseline-adjusted mean difference of 7.34 (5.43 to 9.25) (P < 0.001). The overall complication rate was lower but not statistically significant (24 (9.0) vs. 37 (13.0); RR 0.69 (0.42 to 1.12); P 0.127). Pneumothorax (0.43 (0.22 to 0.85); P 0.012) and pain (0.51 (0.29 to 0.91); P 0.020) were significantly less frequent in the intervention group. Nursing satisfaction was higher in the intervention group (89.90 ± 1.84 vs. 78.06 ± 4.03; mean difference 11.83 (11.31 to 12.35); P < 0.001; Cohen's d = 3.74).</p><p><strong>Conclusion: </strong>In this retrospective real-world study, IMB-based nursing was associated with better patient-reported outcomes and lower risks of pneumothorax and pain after cryoablation. Because the study was non-randomized and unblinded, these findings should be interpreted as associative rather than causal and require prospective confirmation.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lixia Fan, Ruixue Wang, Mingchuang Peng, Qi Song, Yaqian Tan
{"title":"A bibliometric analysis of research hotspots and trends of nitric oxide donors application in cancer therapy from 1995 to 2025.","authors":"Lixia Fan, Ruixue Wang, Mingchuang Peng, Qi Song, Yaqian Tan","doi":"10.1007/s12672-026-05576-y","DOIUrl":"https://doi.org/10.1007/s12672-026-05576-y","url":null,"abstract":"<p><strong>Background: </strong>Nitric oxide (NO) is a critical signaling messenger that maintains normal physiological conditions in the human body. However, the complex roles of NO in cancer biology has stimulated the development of NO donors to achieve controllability and specificity of their anti-tumor effects. We aimed to investigate the research trends and hotspots of the applications of NO donors in cancer therapy from a bibliometric perspective.</p><p><strong>Methods: </strong>Literature associated with the applications of NO donors in cancer treatment published during 1995-2025 was extracted from the Web of Science Core Collection database. VOSviewer and R-bibliometrix were employed to conduct co-author analysis of countries, institutions, and authors, as well as co-occurrence analysis of journals, references, and keywords.</p><p><strong>Results: </strong>A total of 2752 publications were identified and the trends of yearly global production displayed a consistently rising tendency over the past three decades. The USA contributed the most extensive publications and the greatest number of citations in this field. China Pharmaceutical University contributed the most publications and Basil Rigas was the predominant researcher in this research domain. The analysis of keyword co-occurrence indicated that the main research hotspots included \"nitric-oxide\", \"mechanisms\", \"nanoparticles\", \"apoptosis\", \"oxidative stress\", \"synthase\", \"tumor-necrosis-factor\", and \"activation\".</p><p><strong>Conclusion: </strong>Research of NO donors in cancer therapy has received continuous attention over the past three decades and the USA has made significant contributions to this field. The frontiers of this topic have shifted from the broad anti-cancer therapeutic mechanisms of NO to precise molecular mechanisms, and ultimately translated to therapeutically translational applications of NO-based synergistic therapy.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mei Deng, Xueting Wu, Jinhui Bai, Jingzhi Song, Chao Xiong, Huixian Wu, Jie Qin
{"title":"Apoptosis-related TP53AIP1 inhibits breast cancer progression by inactivating the MAPK pathway and serves as a novel prognostic biomarker.","authors":"Mei Deng, Xueting Wu, Jinhui Bai, Jingzhi Song, Chao Xiong, Huixian Wu, Jie Qin","doi":"10.1007/s12672-026-05541-9","DOIUrl":"https://doi.org/10.1007/s12672-026-05541-9","url":null,"abstract":"<p><p>Tumor protein p53-regulated apoptosis-inducing protein 1 (TP53AIP1) has been implicated in tumor suppression, but its role in breast cancer remains unclear. This study evaluated the expression pattern, prognostic value, immune infiltration association, methylation status, and biological function of TP53AIP1 in breast cancer using TCGA transcriptomic data, public methylation datasets, immunohistochemistry, and in vitro experiments. TP53AIP1 was significantly downregulated in breast cancer tissues and was identified as an independent prognostic factor for poor survival. TP53AIP1 expression was positively associated with transcriptome-estimated infiltration of natural killer cells, mast cells, and plasmacytoid dendritic cells. Methylation analysis showed that TP53AIP1 promoter hypermethylation was associated with reduced TP53AIP1 expression, suggesting a potential epigenetic silencing mechanism. Functionally, TP53AIP1 overexpression suppressed breast cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition and, promoted apoptosis and cell-cycle arrest. Mechanistically, TP53AIP1 overexpression reduced MEK/ERK phosphorylation, whereas MAPK pathway reactivation partially reversed its inhibitory effects on malignant phenotypes. These findings suggest that TP53AIP1 may serve as a potential prognostic biomarker and tumor-suppressive candidate in breast cancer, with its effects at least partly associated with MAPK pathway attenuation.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integrative analysis identifies ALDOA and PGK1 as prognostic biomarkers and therapeutic targets in oral squamous cell carcinoma.","authors":"Wenyan Kang, Yanan Hou, Liling Xiang, Lu Wang, Jinghua Shi, Ziqi Yang, Weiyi Chen, Xiuzhen Jia, Tingting Jia, Xusha Chen, Yan Niu","doi":"10.1007/s12672-026-05590-0","DOIUrl":"https://doi.org/10.1007/s12672-026-05590-0","url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinoma (OSCC) is associated with high mortality and limited effective targeted therapies. Although metabolic reprogramming is closely linked to malignancy, the key metabolic regulators that functionally drive OSCC progression and may serve as therapeutic targets remain incompletely defined.</p><p><strong>Methods: </strong>We combined clinical transcriptomic analysis with functional genomic screening to identify metabolic vulnerabilities in OSCC. A Least Absolute Shrinkage and Selection Operator (LASSO)-derived prognostic gene signature was constructed using transcriptomic data from The Cancer Genome Atlas (TCGA)-OSCC cohort. To prioritize functionally critical targets, gene essentiality and tumor selectivity were evaluated using large-scale CRISPR-Cas9 dependency data from the Cancer Dependency Map (DepMap) project.</p><p><strong>Results: </strong>This analysis identified Aldolase A (ALDOA) and Phosphoglycerate Kinase 1 (PGK1) as candidate targets with prognostic relevance and strong dependency across OSCC cell lines. Elevated expression of ALDOA and PGK1 was significantly associated with poor patient survival. Mechanistically, genetic silencing of ALDOA or PGK1 impaired glycolytic activity, as evidenced by reduced extracellular acidification rates (ECAR), and suppressed tumor cell proliferation in vitro and in vivo. Furthermore, combined targeting of these two glycolytic enzymes produced synergistic anti-tumor effects. Bliss independence analysis showed synergy between the ALDOA inhibitor Aldometanib and the PGK1 inhibitor CBR-470-1, and the combination produced greater tumor suppression than either monotherapy in xenograft models.</p><p><strong>Conclusion: </strong>Our findings indicate that ALDOA and PGK1 contribute to metabolic reprogramming and poor prognosis in OSCC. These findings support further evaluation of dual ALDOA and PGK1 inhibition as a potential therapeutic strategy for OSCC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}