by Tomoo Hidaka, Takeyasu Kakamu, Hideaki Kasuga, Yuko Suzuki, Toshihiro Terui, Shizuka Kawamoto, Tatsuya Sato
Municipal government officials (MGOs) have played key roles in managing decontamination project of radioactive materials in the aftermath of the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident. However, the subjective distress experienced by MGOs during the decontamination project, mainly stemming from challenges in coordination with the national government, is not yet fully documented. The purpose of this study is to descriptively understand the nature and causes of subjective distress among MGOs and to make an exploratory conceptual model of the process through which such subjective distress becomes manifest. Narratives from three MGOs were collected through interviews and subjected to qualitative analysis using the Steps for Coding and Theorisation method. For the first purpose, the results indicate that inconsistencies in national reconstruction and decontamination designs impose substantial burdens at the operational level; these burdens are further amplified by inadequate management by national authorities, and subjective distress emerges through a breakdown of trust among national government officials, municipalities, and residents. For the second purpose, an exploratory conceptual model explaining the progression toward subjective distress through the following four stages was created: the emergence of distrust and adversarial orientations toward the national government, the dilemma of occupying an intermediate position, the erosion of ties with residents, and the threat to professional pride. Overall, through experiences such as questioning the national government’s reconstruction policies, enduring the psychological burden of occupying an intermediate position, and witnessing a breakdown in trust with residents, MGOs may find their professional pride undermined; consequently, subjective distress, manifesting as a profound sense of emptiness, may arise. As MGOs are likely to stand at the frontline of managing post-radiation-disaster reconstruction and decontamination efforts, it is essential to develop protective measures for their mental health from both macro-level, organisational perspectives and micro-level, occupational and psychological perspectives.by Xiuxin Liu, Yuhui Han, Ruixue Kuang, Wenjiong Sheng, Yan Zhang, Xinyu Jia, Xiaoxiao Gao, Yanchao Ma
DNA damage-induced by radiotherapy is a critical factor in promoting the death of colorectal cancer cells (CRC). Although high mobility group box 1 (HMGB1) reportedly plays a vital role in tumor radioresistance by modulating DNA damage repair, the precise mechanisms remain unclear. In this study, HMGB1 knockdown markedly enhanced cell apoptosis after radiation. HMGB1 downregulation significantly inhibited DNA damage repair and reactive oxygen species (ROS)-mediated redox homeostasis after irradiation in CRC cells. Mechanistically, HMGB1 interacts with KU70 via its region spanning residues 95–163. This interaction subsequently activates the non-homologous end joining (NHEJ) pathway to facilitate DNA damage repair, ultimately leading to reduced radiation-induced cell apoptosis. KU70 silencing showed the same effect as HMGB1 depletion mediated cell apoptosis and DNA damage response both in vitro and in vivo. Additionally, HMGB1 and KU70 were overexpressed in CRC tissues. Analysis of the GEPIA database indicated that elevated levels of both genes showed a trend toward association with poor patient prognosis, although this did not reach statistical significance. The current study revealed that HMGB1 may promote DNA damage repair through KU70 and its mediated NHEJ pathway to affect apoptosis in CRC cells after irradiation. Thus, targeting the HMGB1/KU70/NHEJ axis may be a potential therapeutic target to promote the response of CRC to radiotherapy and in-depth study of the specific mechanism of this axis in CRC radioresistance will help to the develop more effective treatment strategies.by Hang Sun, Haozhi Xu, Junying Li, Xiaoman Xie, Junmei Zhang, Hongjie Dong, Huanhuan Xie, Qi Wang, Guihua Zhao, Kun Yin, Jingyu Yang, Jianwei Zhou, Ruili Wu, Chao Xu
Gastric cancer (GC) is one of the most common and lethal cancers globally. methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) RNA methylation plays a crucial role in tumor initiation and progression by regulating RNA function. STM2457, a highly efficient METTL3 inhibitor, can inhibit METTL3 activity and may serve as a potential therapeutic strategy in cancers. However, the role of STM2457 for GC cells is still unknown. In this study, we analyzed the expression profile data of GC in TCGA and GEO databases, and further explored the expression involvement of METTL3 in GC cell line, investigated the therapeutic effect of STM2457 targeted inhibition of METTL3 in GC both in vitro and in vivo experiments. The results indicated that STM2457 could suppress GC cell proliferation and migration by inhibiting METTL3, and also promoted cell apoptosis and arrest the cell cycle in S phase. In addition, STM2457 could inhibit tumor growth in subcutaneous xenotransplantation mouse model. Our findings suggested that STM2457 had great potential for the treatment of GC and could serve as a foundation for future clinical applications.To explore the complex relationships among non-suicidal self-injury, depression and anxiety symptoms in adolescents, identify key symptoms and provide a theoretical foundation for targeted interventions.
A cross-sectional study.
In total, 1126 adolescents from a tertiary hospital in Shandong Province were assessed using the Adolescent Self-Injury Questionnaire, Patient Health Questionnaire and Generalised Anxiety Disorder Scale. Network analysis was employed to construct symptom networks and identify central and bridging symptoms.
The network analysis revealed that nodes GAD5 (Restlessness), GAD2 (Uncontrollable worry), and GAD4 (Trouble relaxing) exhibited the highest centrality indices, establishing them as core symptoms within the overall symptom network. The highest bridge intensity nodes were GAD1 (Nervousness), GAD5 (Restlessness) and non-suicidal self-injury.
By accurately identifying core and bridging symptoms, a scientific foundation is provided for developing precise and effective symptom management plans.
The study identified the most influential nodes in anxiety and depression among adolescents with non-suicidal self-injury. The findings would help in carrying out personalised and precise interventions to reduce non-suicidal self-injury occurrence and alleviate anxiety and depression symptoms among adolescents.
This study adheres to the STROBE guideline of reporting.
This study did not include patient or public involvement in its design, conduct or reporting.
To identify adverse outcomes and factors associated with diabetes mellitus among children and youths in East Africa.
This review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
No date restrictions were applied to searches of the Ovid MEDLINE, Embase, PubMed, CINAHL, Scopus, Web of Science, Cochrane Library databases and Google Scholar. The review identified and included literature published between 2007 and 2024.
Independent reviewers conducted study selection, data extraction, and quality assessment. Data were organised in Microsoft Excel, detailing study characteristics, demographics, exposures, and outcomes. Narrative synthesis summarised the data, while meta-analysis yielded pooled proportions.
From 3797 publications, 30 studies involving 6109 children and youths with type 1 diabetes were included. Findings revealed that between 39.3% and 99% did not achieve target glycaemic levels. Diabetic ketoacidosis at diagnosis ranged from 35.8% to 78.7%. Pooled estimates indicated mortality in 6.47%, nephropathy in 15.66%, and retinopathy in 27.49% of the cases. Other complications included decreased health-related quality of life, lipodystrophy, psychiatric disorders, and stunting.
This review highlights the need for context-specific, personalised diabetes care for children and youths in East Africa. It underscores the need for healthcare professionals, particularly nurse diabetes educators, to provide personalised, holistic care and education. Policies that strengthen health systems, expand health insurance, and improve access to care are critical priorities to improve outcomes for these populations.
This study provides new information on diabetes-related complications and management challenges among children and youths in East Africa. Findings flag the urgent need for integrated care, standardised diagnostic criteria, and improved access to resources, with implications for healthcare providers, policymakers, and researchers to enhance health outcomes and quality of life.
This study did not include patient or public involvement in its design, conduct, or reporting.
To consolidate and synthesise the literature reporting perceptions of nurses and nursing students regarding evidence-based nursing.
Qualitative systematic review.
Seven electronic databases (Cumulative Index to Nursing and Allied Health Literature, Embase, ProQuest Dissertations & Theses Global, PsycInfo, PubMed, Scopus and Web of Science) were searched from their respective inception dates to January 2025.
The Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines guided this review. The quality of included studies was assessed using the Critical Appraisal Skills Programme tool, and data were synthesised thematically using Sandelowski and Barroso's two-step approach.
Thematic analysis of the 19 included studies, published from 2007 to 2025, identified three key themes: (1) Advancing nursing through evidence, (2) Personal, structural and systemic challenges and (3) Promoting a new evidence-based nursing culture.
Evidence-based nursing can elevate nursing care standards and enhance patient outcomes. Numerous factors that encourage and hinder the implementation of evidence-based nursing among nurses and nursing students were reported.
This review suggests the need to incentivise nurses to champion evidence-based nursing initiatives, provide nurses and nursing students with continuing education, and develop updated evidence-based nursing guidelines. These strategies could help in cultivating a supportive evidence-based nursing workplace culture and improving the implementation of evidence-based nursing.
Valuable insights into the facilitators and barriers associated with the implementation of evidence-based nursing were reported by nurses and nursing students—the key personnel responsible for practising evidence-based nursing. Future research could be undertaken to explore the perceptions of nurses and nursing students across varied cultural settings and in underrepresented regions.
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.
This study did not include patient or public involvement in its design, conduct, or reporting.
To measure and compare the temporal variations in sub-bandage pressure compression systems in the Andalusian Health System (SAS). Additional objectives included assessing the relationship between pressure and healing, analysing the influence of the healthcare professional applying the bandage, and determining bandage stiffness. This prospective observational and multicentre study included 140 patients with active VLUs in Andalusia. Sub-bandage pressures were measured at three anatomical points in the leg for 96 h, under different positions and activities. The bandage application technique was standardised through specific training provided to advanced practice nurses. The initial pressures were higher than those recommended by guidelines, but showed a notable reduction within the first 24 h, stabilising within therapeutic ranges for the remainder of the 96-h study period. Most systems showed low dynamic and static stiffness. No significant pressure differences were found attributable to the nurses or the location of the injury. The observed pressure dynamics, initially high, with a subsequent drop and final stabilisation, suggest a high material settlement or application to compensate for the expected loss. The sustained pressure stability confirms the effectiveness of the systems over 96 h.
Negative pressure wound therapy (NPWT) is widely used to facilitate healing by improving local perfusion, reducing edema and controlling exudate. The porous foam dressing is central to NPWT effectiveness, however, its performance in viscous, particle-rich exudates remains challenging. Standard industry tests often rely on protein-free aqueous solutions, which overlook the complex rheology and particulate load of real wounds. This study reports a bench evaluation of a multilayer foam prototype compared with three commercial dressings under NPWT, using a simulated viscous exudate with suspended particles. We recorded 60-min drainage curves and quantified effluent turbidity as a simple, interpretable proxy for particulate transport, summarised as percentage of input turbidity recovered. The mass-based endpoint (percent solid matter recovered) showed the same ranking as turbidity. At −75 mmHg, the prototype recovered 31.6% of input turbidity, exceeding commercial foams (≤ 9.7%). At −125 mmHg, particulate recovery decreased across all dressings (≤ 9.1%). A matrix-only control indicated that commercial effluents, particularly at −75 mmHg, clustered near background level, whereas the prototype evacuated substantially more particulate while maintaining robust fluid drainage. These findings suggest that moderate negative pressure and multilayer architecture can help preserve channel patency and reduce clogging in complex exudates. We highlight the need for test methodologies that incorporate viscosity and particulate content, and for practical guidance that links dressing architecture and pressure settings to exudate characteristics. Prospective validation, including larger-sample confirmation, particle-size distributions and ultimately clinical endpoints, is warranted.
by Xiaocan Li, Rui Min
PurposeObesity is strongly associated with hepatocellular carcinoma (HCC), yet the molecular mechanisms linking them remain unclear. This study aimed to identify mitochondrial metabolism-related genes bridging obesity and HCC and to investigate their role in regulating the metabolic-immune microenvironment.
MethodsPublic transcriptomic datasets from obesity (derived from peripheral blood mononuclear cells) and HCC (derived from liver tissue) cohorts were integrated. A multi-step bioinformatic pipeline combining differential expression analysis (DEA), weighted gene co-expression network analysis (WGCNA), and machine learning (ML) algorithms was applied to identify and validate hub genes. Associations with the tumor immune microenvironment were assessed using ssGSEA and correlation analyses.
Results27 core genes were identified, significantly enriched in lipid metabolism and immune response pathways. Among these, ML highlighted ACAA1 and ADI1 as downregulated candidate genes. While discovery datasets showed high diagnostic potential, ADI1 exhibited more variable performance in obesity external validation compared to the robust consistency of ACAA1. Downregulation of both genes correlated with effector T/NK cell lipid-mediated functional exhaustion and disrupted networks of immune checkpoints and chemokines, reflecting an immunosuppressive microenvironment.
ConclusionsACAA1 and potentially ADI1 are downregulated candidate genes linking obesity to HCC. Their suppression likely drives obesity-related HCC progression by coupling mitochondrial metabolic reprogramming with immunosuppressive tumor microenvironment remodeling, representing potential therapeutic targets.
Skin temperature, including absolute temperature (at bony prominence areas under long-term compression) and relative temperature (the difference between bony prominence and adjacent control area), may serve as early warning indicators for PI. However, the optimal indicator remains unclear. This meta-analysis therefore synthesises evidence on their association with PI risk to identify the best indicator and evaluate its early-warning accuracy.
Systematic review and meta-analysis.
We included prospective cohort studies of adult patients investigating longitudinal associations between skin temperature and subsequent PI development. We pooled standardised mean difference (SMD) and odds ratios, complemented by summary receiver operating characteristic (SROC) curve analysis. The overall quality of evidence was evaluated using the GRADE method.
We researched PubMed, Embase, CINAHL, Cochrane Library (CENTRAL), Wanfang and CNKI databases from inception to September 25, 2024.
After screening 1354 titles and abstracts, ten studies comprising 1742 participants were included in the final synthesis. No significant difference in absolute temperature (combined SMD) was found between the PI and non-PI groups (seven studies included). In addition, decreased relative temperature (< −0.1°C) was associated with a 16-fold increased likelihood of PI (95% CI 6.38–40.19, I 2 = 79.4%) (three studies included), with the SROC curve analysis showing an AUC of 0.776. According to GRADE, the evidentiary certainty was very low for AT and low for RT.
Relative temperature is significantly related to the risk of PI, supporting its role as a promising early warning indicator. Future studies should establish a standardised measurement protocol to facilitate its clinical application.
Monitoring skin temperature changes holds promise as a non-invasive tool for early warning of PI risk. However, the amount and quality of available evidence limit our confidence in these findings, underscoring the need for further research before a definitive conclusion can be drawn.
This study followed PRISMA guidelines.
No patient or public contribution.
PROSPERO CRD42024550099
To identify and describe instruments used to assess obstetric violence and evaluate their methodological quality and psychometric properties.
A scoping review.
Ten databases [Medline (via PubMed), Web of Science, the Cochrane Library, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), SinoMed, Wanfang Database, China National Knowledge Infrastructure (CNKI), VIP Database and China Medical Journal Full-text Database] were searched from inception to June 2025.
Studies focusing on the development or validation of obstetric violence measurement tools were eligible for this review. Methodological quality and psychometric properties were evaluated using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist and criteria.
A total of 19 studies encompassing 25 obstetric violence measurement tools were included. These studies were conducted in 15 countries between 2018 and 2025. The tools targeted postnatal and pregnant women, healthcare providers, students and other populations. Most studies reported data on content validity, structural validity and internal consistency. Limited information was available on cross-cultural validity/measurement invariance, reliability, measurement error, criterion validity, hypotheses testing for construct validity and responsiveness.
This review identified multiple obstetric violence instruments used across diverse populations and settings. Whilst the methodological quality and measurement properties of the included tools were sub-optimal, they nevertheless provide a foundation for the timely assessment of obstetric violence and subsequent research.
Future research should prioritise the establishment of a unified definition of obstetric violence, alongside the development, adaptation and rigorous validation of measurement instruments to enhance their reliability and validity.
This review underscores the need for maternity care professionals and educators to critically evaluate existing tools for measuring obstetric violence, given their current methodological limitations.
The PRISMA Extension for Scoping Reviews (PRISMA-ScR) checklist.
No patient or public contribution.
by Hongfei Yang, Chao Sun, Ya Li, You Zhou, Rui Wang, Yingxue Li
ObjectiveThe triglyceride-glucose index and estimated glucose disposal rate serve as notable surrogate markers of insulin resistance, demonstrating established links to cardio-cerebrovascular disease. However, their combined prognostic value in predicting cardio-cerebrovascular disease outcomes remains unexplored. The current investigation examined the interaction between the TyG (triglyceride–glucose index) index and eGDR (estimated glucose disposal rate) concerning the danger of cardiovascular disease within a clinical population.
MethodsThis investigation employed data sourced from the China Health and Retirement Longitudinal Study (CHARLS). The median TyG index and eGDR scores were used to stratify the participants into 4 categories: low TyG/high eGDR, high TyG/high eGDR, low TyG/low eGDR, and high TyG/low eGDR. Clinical characteristics across groups were systematically compared. Cox proportional hazards regression models evaluated the distinct and interconnected associations of the TyG index and eGDR with the risk of cardio-cerebrovascular disease, with multiplicative and additive interaction effects subsequently assessed through formal interaction analysis.
ResultsThe final study cohort comprised 7,330 participants, with 1,336 individuals (18.2%) developing cardio-cerebrovascular disease during the 9-year follow-up. Stratification using median thresholds (TyG: 8.59; eGDR: 10.55 mg/kg/min) yielded four groups: low TyG/high eGDR (n = 2,991), high TyG/high eGDR (n = 1,375), low TyG/low eGDR (n = 1,372), and high TyG/low eGDR (n = 2,292). Multivariable-adjusted Cox regression analyses revealed markedly increased risks of cardio-cerebrovascular disease among the various exposure groups when contrasted with the low TyG/high eGDR reference: high TyG/high eGDR (HR: 1.31, 95%CI: 1.10–1.57, ppp Conclusion
The TyG index and eGDR demonstrate independent associations with cardio-cerebrovascular disease risk, while their combined assessment reveals synergistic predictive capacity. Combined assessment of the two allows for further accurate stratification of the population based on insulin resistance and improved prediction of cardio-cerebrovascular disease.
To explore survivors' perspectives and experiences of psychological detachment while living with a stoma.
A qualitative descriptive study was conducted. This study followed the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist.
A total of 15 semi-structured interviews were conducted between February 2024 and May 2024. The phenomenological method proposed by Colaizzi was used to analyze the data.
Four major themes emerged from the analysis: (1) Trapped in the Persistent Impact of Dual Traumas: Struggles with Adaptation; (2) Trapped by the Unrelenting Burden of Stoma Care: A Cycle of Powerlessness; (3) Trapped by the Shackles of a Stigmatised Identity: The Dilemma of Social Reintegration; and (4) Divergent Pathways of Detachment: Navigating Between Immersion and Transcendence. Within the main themes, eight subthemes were formulated.
This study thoroughly explored and elucidated the psychological detachment experiences of colorectal cancer survivors with a stoma, revealing its key role in mental health recovery and psychosocial rehabilitation and informing clinical interventions.
The study suggests that healthcare staff should guide survivors in drawing a clear boundary between stoma care and their personal life, encourage any correction of erroneous social cognition, and promote the positive development of psychological detachment among survivors.
This study explored the challenges of psychological detachment in stoma survivors, identifying key barriers like trauma, care burden, role misconceptions, and varying detachment levels. The findings can guide healthcare providers in supporting survivors' mental well-being and inform better survivorship care strategies.
There was no patient or public contribution.
This study aimed to (1) evaluate the effectiveness of e-health interventions in improving physical activity and associated health outcomes during pregnancy, (2) compare the e-health functions employed across interventions and (3) systematically identify the behaviour change techniques (BCTs) used and examine their interrelationships.
A systematic review and meta-analysis following the PRISMA 2020 guidelines.
Randomised controlled trials were included. Meta-analyses and subgroup analyses were performed using RevMan 5.3. Social network analysis was conducted to determine the most central BCTs within the intervention landscape.
Ten databases were searched, including PubMed, Embase, Web of Science, Cochrane Library, ProQuest, Scopus, SinoMed, China National Knowledge Infrastructure, WanFang and the China Science and Technology Journal Database, from inception to April 22, 2024.
Thirty-five studies were included. Pooled analyses indicated that e-health interventions significantly improved both total (SMD: 0.19; 95% CI: 0.10 to 0.27; I 2 = 55%) and moderate-to-vigorous physical activity (SMD: 0.16, 95% CI: 0.06 to 0.26; I 2 = 53%) in pregnant women. Subgroup analyses revealed that interventions based on theoretical frameworks and those not specifically targeting overweight or obese women demonstrated greater effectiveness. Additionally, e-health interventions were associated with significant reductions in both total and weekly gestational weight gain. Six of the twelve e-health functions were utilised, with ‘client education and behaviour change communication’ being the most prevalent. Thirty unique BCTs were identified; among them, ‘instruction on how to perform the behaviour’, ‘self-monitoring’, ‘problem solving’, and ‘goal setting’ showed the highest degree of interconnectedness.
E-health interventions are effective in enhancing physical activity and reducing gestational weight gain during pregnancy. Incorporating theoretical frameworks and well-integrated BCTs is recommended to optimise intervention outcomes.
Integrating e-health interventions into existing perinatal care models holds promise for enhancing physical activity among pregnant women and improving maternal health outcomes.
This study adhered to the PRISMA checklist.
No patient or public involvement.
The study protocol was preregistered in the International Prospective Register of Systematic Reviews (CRD42024518740)
Información relativa a las próximas Jornadas Internacionales de Cultura de los Cuidados que se celebrarán en Alicante (Sede Universidad de Alicante) durante los días 29 y 30 de junio de 2026
To explore the lived experience of young people aged 16–24 years diagnosed with melanoma and that of their significant other in England.
Interpretive phenomenological analysis.
Data were collected between August 2023 and January 2024 from one specialist cancer centre in England. Thirteen young people were approached, and 10 took part. Each young person was asked to nominate a significant other. Five nominated a significant other, and five nominated no one. Although interviews were offered face-to-face, virtual was the preferred method. In-depth semi-structured interviews were audio-recorded with the participant's consent. Interview data were transcribed verbatim and analysed.
The core conceptual thread woven throughout the findings was ‘It's like being on a rollercoaster,’ which is representative of the ups and downs of the treatment trajectory, often without the support of age-appropriate specialist care. Four superordinate themes were identified: ‘Is something wrong?’, ‘Suddenly it's serious’, ‘Out on a limb’ and ‘Finding our place’.
Although most young people were treated in a primary treatment centre for adults with cancer, their experience was challenging from route to diagnosis through their treatment and beyond. Few received age-appropriate care to support their physical, emotional, and social wellbeing to help them navigate the experience.
There is limited evidence exploring the experiences of teenagers and young adults living with melanoma or that of their significant other. This enriched understanding supports improvement of the care pathway and service delivery for these young people and their families.
One young person with lived experience was paid as a consultant to be part of the research team. He helped develop the grant application and research questions, data analysis, and writing this paper.
The study examines the associations between nursing competence, work environment, and health system resilience. It also analyzes how nursing competence and work environment relate to different patterns of health system resilience.
A multiple center cross-sectional study was conducted between December 2023 and January 2024 across 33 hospitals in eastern China, involving 2435 nurses.
Questionnaires measuring nursing competence, work environment resources, nurse disaster resilience, and organizational commitment to resilience were utilised, along with the collection of additional personal demographic data. Structural equation modelling and cluster analysis were performed to explore the underlying mechanisms within the overall model and across multiple groups. Multivariable regression was conducted to identify variables associated with resilience in different subgroups.
Structural equation modelling demonstrated significant influences of nursing competence and work environment support on system resilience. Cluster analysis identified four resilience patterns: strong, marginal, low, and critical vulnerability. Strong resilience correlated with balanced individual-organizational resources, while vulnerable systems relied heavily on environmental support.
Our findings support policymakers and managers in developing systematic strategies with distinct focal points—targeting nurse workforce investment and optimised work environment—to enhance health system resilience across varying levels of public health emergencies.
This study validated the framework connecting individual and organizational resilience, offering evidence-based insights for nurse training and resource allocation to enhance healthcare systems' adaptability during disasters.
The study addressed how nursing competence and work environment significantly influenced resilience during public health emergencies, identified four resilience patterns, and provided insights to guide policymakers and healthcare managers in developing targeted, effective strategies.
Strengthening the Reporting of Observational studies in Epidemiology checklist.
No patient or public contribution.
by Xinrui Zhao, Jie Li, Nan Hu, Xiaoming Wu, Junbo Duan
Amino acid metabolism plays a critical role in tumor growth and immune regulation, yet its comprehensive function in breast cancer remains underexplored. We developed an amino acid metabolism–related gene signature (AAMRGS) to predict prognosis and therapeutic response in breast cancer. The AAMRGS was constructed using a machine-learning framework integrating ten algorithms and validated across multiple independent cohorts. It served as an independent prognostic factor and outperformed existing amino acid metabolism–related signatures and clinical variables. Moreover, the prognostic utility of AAMRGS was further validated across pan-cancer datasets, and an AAMRGS-based nomogram was constructed to facilitate clinical application. Functional enrichment and protein–protein interaction analyses revealed that AAMRGS genes were primarily involved in metabolic reprogramming and cell proliferation. Experimental validation confirmed the downregulation of key genes such as SAV1 and IGF2R in breast cancer cells. Integrative analyses revealed that the high-AAMRGS subgroup exhibited a greater copy number variation burden, higher tumor mutation burden (TMB), enrichment of immunosuppressive cell populations, and increased sensitivity to most chemotherapeutic drugs. In contrast, the low-AAMRGS subgroup displayed higher immune scores, stronger immune activation, enrichment of anti-tumor immune cells, and greater responsiveness to immunotherapy. Collectively, our findings establish AAMRGS as a reliable prognostic signature and a potential tool to guide individualized therapeutic strategies for breast cancer patients.