bims-meluca Biomed News
on Metabolism of non-small cell lung carcinoma
Issue of 2025–08–10
four papers selected by
the Muñoz-Pinedo/Nadal (PReTT) lab, L’Institut d’Investigació Biomèdica de Bellvitge



  1. J Cachexia Sarcopenia Muscle. 2025 Aug;16(4): e70021
       BACKGROUND: AI-driven automated body composition analysis (BCA) may provide quantitative prognostic biomarkers derived from routine staging CTs. This two-centre study evaluates the prognostic value of these volumetric markers for overall survival in lung cancer patients.
    METHODS: Lung cancer cohorts from Hospital A (n = 3345, median age 65, 86% NSCLC, 40% M1, 40% female) and B (n = 1364, median age 66, 87% NSCLC, 37% M1, 38% female) underwent automated BCA of abdominal CTs ±60 days of primary diagnosis. A deep learning network segmented muscle, bone and adipose tissues (visceral = VAT, subcutaneous = SAT, intra-/intermuscular = IMAT and total = TAT) to derive three markers: Sarcopenia Index (SI = Muscle/Bone), Myosteatotic Fat Index (MFI = IMAT/TAT) and Abdominal Fat Index (AFI = VAT/SAT). Kaplan-Meier survival analysis, Cox proportional hazards modelling and machine learning-based survival prediction were performed. A survival model including clinical data (BMI, ECOG, L3-SMI, -SATI, -VATI and -IMATI) was fitted on Hospital A data and validated on Hospital B data.
    RESULTS: In nonmetastatic NSCLC, high SI predicted longer survival across centres for males (Hospital A: 24.6 vs. 46.0 months; Hospital B: 13.3 vs. 28.9 months; both p < 0.001) and females (Hospital A: 37.9 vs. 53.6 months, p = 0.008; Hospital B: 23.0 vs. 28.6 months, p = 0.018). High MFI indicated reduced survival in males at both hospitals (Hospital A: 43.7 vs. 28.2 months; Hospital B: 28.8 vs. 14.3 months; both p ≤ 0.001) but showed center-dependent effects in females (significant only in Hospital A, p < 0.01). In metastatic disease, SI remained prognostic for males at both centres (p < 0.05), while MFI was significant only in Hospital A (p ≤ 0.001) and AFI only in Hospital B (p = 0.042). Multivariate Cox regression confirmed that higher SI was protective (A: HR 0.53, B: 0.59, p ≤ 0.001), while MFI was associated with shorter survival (A: HR 1.31, B: 1.12, p < 0.01). The multivariate survival model trained on Hospital A's data demonstrated prognostic differentiation of groups in internal (n = 209, p ≤ 0.001) and external (Hospital B, n = 361, p = 0.044) validation, with SI feature importance (0.037) ranking below ECOG (0.082) and M-status (0.078), outperforming all other features including conventional L3-single-slice measurements.
    CONCLUSION: CT-based volumetric BCA provides prognostic biomarkers in lung cancer with varying significance by sex, disease stage and centre. SI was the strongest prognostic marker, outperforming conventional L3-based measurements, while fat-related markers showed varying associations. Our multivariate model suggests that BCA markers, particularly SI, may enhance risk stratification in lung cancer, pending centre-specific and sex-specific validation. Integration of these markers into clinical workflows could enable personalized care and targeted interventions for high-risk patients.
    Keywords:  body composition analysis; deep learning; lung cancer; myosteatosis; sarcopenia
    DOI:  https://doi.org/10.1002/jcsm.70021
  2. Biomark Med. 2025 Aug 03. 1-10
       AIM: Metastatic non-small cell lung cancer (NSCLC) patients face a poor prognosis, with a 5-year overall survival (OS) rate of under 10%. In this investigation, we examined the prognostic implications of sarcopenia and metabolic metrics obtained from 18F-FDG PET/CT imaging in individuals diagnosed with metastatic non-squamous NSCLC (nsNSCLC).
    METHODS: The investigation included 124 individuals with metastatic nsNSCLC who underwent 18F-FDG PET/CT imaging on diagnosis. Sarcopenia was determined by evaluating the skeletal muscle index at the L3 vertebral level. Metabolic metrics obtained from 18F-FDG PET/CT imaging, maximum standard uptake, metabolic tumor volume, and total lesion glycolysis were measured for whole body lesions (SUVmax_WB, MTV_WB, and TLG_WB) and primary tumors (SUVmax_T, MTV_T, and TLG_T). Primary endpoints examined were OS and the rate of sarcopenia diagnosis.
    RESULTS: Patients with sarcopenia, comprising 74.2% of the cohort, experienced a markedly reduced median OS of 4.7 months compared to 9.8 months in the non-sarcopenic cohort, which accounted for 25.8% of the population. Multivariate analysis revealed that sarcopenia, as well as metabolic metrics, including SUVmax_T, MTV_T, TLG_T, and SUVmax_WB, were independent predictors of OS in metastatic nsNSCLC patients.
    CONCLUSION: The presence of sarcopenia and unfavorable metabolic metrics on 18F-FDG PET/CT are linked to worse survival outcomes in metastatic nsNSCLC patients.
    Keywords:  MTV; PET/CT; SUVmax; Sarcopenia; TLG; non-squamous NSCLC; prognosis
    DOI:  https://doi.org/10.1080/17520363.2025.2540758
  3. Discov Oncol. 2025 Aug 04. 16(1): 1464
       BACKGROUND: This study aims to establish a hypoxia-immune-related gene signature within the tumor microenvironment (TME) to reliably predict prognosis in non-small cell lung cancer (NSCLC).
    METHODS: Transcriptomic profiles and clinical data of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases (GSE74777, GSE68465). Hypoxia- and immune-related genes were curated from MSigDB, ImmPort, and INATDB. Prognostic genes were identified via Cox and LASSO regression analyses, and a risk model was constructed. Model validity was assessed through Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, and external validation.
    RESULTS: An eight-gene prognostic signature (AKAP12, MT2A, SERPINE1, CD1E, CD79A, CXCL13, XCL2, ANGPTL4) was established. The model demonstrated significant predictive accuracy for NSCLC survival (AUC: 0.643/0.649/0.620 at 1/3/5 years in TCGA cohort). Patients with high immune activity exhibited superior survival outcomes compared to those with low-immune counterparts (log-rank P < 0.001). Multivariate Cox regression confirmed the risk score as an independent prognostic factor (HR = 1.82, 95% CI: 1.44-2.30, P < 0.001).
    CONCLUSIONS: The hypoxia-immune microenvironment signature serves as a robust prognostic classifier for NSCLC, providing a quantitative framework for personalized risk stratification and clinical decision support.
    Keywords:  Genetic markers; Hypoxia; Immunity; Non-small cell lung cancer; Prognostic model
    DOI:  https://doi.org/10.1007/s12672-025-03319-z
  4. Int Immunopharmacol. 2025 Aug 02. pii: S1567-5769(25)01284-6. [Epub ahead of print]163 115293
       BACKGROUND: To investigate the role of PRKR-like Endoplasmic Reticulum Kinase (PERK) pathway in the development of osteosarcoma, its impact on the polarization and metabolism of Tumor-Associated Macrophages (TAMs), and its potential as a therapeutic target.
    RESULTS: High PERK expression is associated with poor survival and increased M2 macrophage infiltration in osteosarcoma patients. Inhibition of PERK promotes the polarization of TAMs towards the anti-tumor M1 phenotype, enhances glycolytic metabolism, and reduces immunosuppression. Additionally, PERK inhibition induces endoplasmic reticulum (ER) stress and apoptosis in osteosarcoma cells, thereby enhancing the cytotoxic effect of TAMs on osteosarcoma cells. In vivo experiments demonstrated that GSK2606414 significantly slows tumor growth in the osteosarcoma mouse model and increases the immune infiltration of M1 macrophages.
    CONCLUSION: Inhibition of the PERK pathway could exacerbate ER stress and promote apoptosis in osteosarcoma cells, while also altering the polarization state of TAMs from the immunosuppressive M2 phenotype to the anti-tumorigenic M1 phenotype, thereby disrupting tumor immunosuppression. This study provides a new perspective on the biological mechanisms of osteosarcoma and opens up a new direction for its therapeutic strategies.
    Keywords:  ER stress; Glycolysis; M1 polarization; Osteosarcoma; PERK pathway; Tumor-associated macrophages
    DOI:  https://doi.org/10.1016/j.intimp.2025.115293