bims-meluca Biomed News
on Metabolism of non-small cell lung carcinoma
Issue of 2025–01–12
seven papers selected by
the Muñoz-Pinedo/Nadal (PReTT) lab, L’Institut d’Investigació Biomèdica de Bellvitge



  1. Cancers (Basel). 2024 Dec 12. pii: 4146. [Epub ahead of print]16(24):
       BACKGROUND: Immunotherapy has transformed cancer treatment; however, predicting treatment response remains challenging. Serum biomarkers can help identify patients who are most likely to benefit from immunotherapy.
    OBJECTIVE: This study evaluates the relationship between serum growth differentiation factor 15 (GDF-15) and interleukin-6 (IL-6) levels and treatment outcomes in cancer patients undergoing second-line immunotherapy.
    METHODS: We conducted a prospective observational study involving 85 patients with non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), or malignant melanoma treated with nivolumab. The baseline serum levels of GDF-15 and IL-6 were measured by using ELISA kits. The primary endpoints were progression-free survival (PFS) and overall survival (OS), with cachexia as a secondary outcome.
    RESULTS: Elevated GDF-15 levels were significantly associated with shorter PFS (HR: 0.55, 95% CI: 0.32-0.96, p = 0.032) and OS (HR: 0.47, 95% CI: 0.25-0.90, p = 0.020). Higher IL-6 levels correlated with shorter PFS, though statistical significance was not achieved. Additionally, high GDF-15 levels were linked to increased cachexia incidence (p = 0.037).
    CONCLUSION: Our findings indicate that GDF-15 could serve as a prognostic biomarker for immunotherapy response and may also be a target for cachexia management. Further studies should explore its potential to guide clinical decision making in oncology.
    Keywords:  Growth Differentiation Factor 15 (GDF-15); Interleukin-6 (IL-6); immunotherapy response
    DOI:  https://doi.org/10.3390/cancers16244146
  2. Discov Oncol. 2025 Jan 04. 16(1): 8
       OBJECTIVE: The purpose of this study is to analyze the predictive value of neutrophil to lymphocyte ratio (NLR), lymphocyte count to monocyte count ratio (LMR), platelet to lymphocyte ratio (PLR), platelet count multiplied by neutrophil count to lymphocyte count ratio (SII), red blood cell distribution width (RDW), packed cell volume (PCV), and plateletcrit (PCT) levels in advanced non-small cell lung cancer (NSCLC) patients treated with PD-1/PD-L1 inhibitors.
    MATERIALS AND METHODS: From March 2019 to August 2023, we screened 104 of 153 patients with stage III unresectable local advanced NSCLC and IV NSCLC who received PD-1/PD-L1 inhibitor therapy at our hospital and met the inclusion and exclusion criteria for analysis. All patients were collected for clinical information, including baseline blood indicator (NLR, PLR, LMR, SII, CRP, RDW, PCV and PCT) levels before PD-1/PD-L1 inhibitor therapy and blood indicator levels and imaging evaluation results every two cycles after PD-1/PD-L1 inhibitor therapy. We analyzed the predicted impact of baseline blood indicators on PD-1/PD-L1 inhibitor treatment response, the discriminatory power of blood indicators on treatment response after efficacy evaluation, and the dynamic changes in blood indicators during PD-1/PD-L1 inhibitor treatment.
    RESULTS: In our study data, baseline levels of NLR, PLR, LMR, SII, CRP, RDW, PCV, and PCT did not provide good predictive identification of PD-1/PD-L1 inhibitor primary resistance and effective treatment response populations. These indicators showed no significant distribution differences in Mann Whitney Wilcoxon analysis, univariate and multivariate logistic regression analysis between the primary resistance group and the effective treatment response group. We validated the NLR threshold of 5 from multiple previous studies in the data of this study, and patients with NLR > 5 also did not show a significant tendency towards the primary resistance group. The levels of NLR, PLR, LMR, SII, CRP, RDW, PCV, and PCT after efficacy evaluation also cannot effectively distinguish primary drug resistance and effective treatment response populations. However, in the longitudinal data analysis before and after PD-1/PD-L1 inhibitor treatment, we found that the NLR, SII, and CRP levels of patients who responded effectively were significantly reduced compared to baseline status. But this phenomenon was not observed in PD patients.
    CONCLUSIONS: PD-1/PD-L1 inhibitors treatment significantly altered the levels of NLR, SII, and CRP in patients with advanced NSCLC. Dynamic monitoring of NLR, SII, and CRP levels may have potential application value in monitoring the therapeutic efficacy of ICIs. In our study, the baseline status of blood indicator levels did not achieve good primary drug resistant patient identification. The potential value of blood indicators in predicting primary resistance to ICI should be further explored in larger research cohorts.
    Keywords:  Immune checkpoint inhibitor; Inflammatory MARKERS; Non-small cell lung cancer; Therapeutic effect prediction
    DOI:  https://doi.org/10.1007/s12672-025-01753-7
  3. J Proteome Res. 2025 Jan 08.
      Non-small cell lung cancer (NSCLC) is frequently diagnosed late and has poor survival. The two predominant subtypes of NSCLC, adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), are currently differentially diagnosed using immunohistochemical markers; however, they are increasingly recognized as very different cancer types suggestive of potential for new, more targeted therapies. There are extensive efforts to find more precise and noninvasive differential diagnostic tools. Here, we examined these two NSCLC subtypes for differences that may inform treatment and identify potential novel therapeutic pathways. We presented a comparative analysis of transcriptomic and proteomic expression in tumors from a cohort of 22 NSCLC patients: 8 LUSC and 14 LUAD. Comparing NSCLC subtypes, we found differential gene expression related to cell differentiation for LUSC and cellular structure and immune response regulation for LUAD. Differential protein expression between NSCLC subtypes was related to extracellular structure for LUSC and metabolic processes, including glucose metabolism for LUAD. This direct comparison was more informative about subtype-specific pathways than between each subtype and control (nontumor) tissues. Many of our observations between NSCLC subtypes support and inform existing observations and reveal differences that may aid research seeking to identify and validate novel subtype biomarkers or druggable targets.
    Keywords:  gene expression; non-small cell lung cancer; proteomics
    DOI:  https://doi.org/10.1021/acs.jproteome.4c00773
  4. BMC Cancer. 2025 Jan 06. 25(1): 17
       INTRODUCTION: The systemic immune-inflammation index (SII) has emerged as a promising prognostic marker in various malignancies. However, its prognostic significance in patients with small-cell lung cancer (SCLC) treated with immune checkpoint inhibitors (ICIs) remains unclear. In this study, we evaluated the prognostic impact of the SII in patients with SCLC after ICI use.
    METHODS: Of 62 patients with SCLC who received chemoimmunotherapy at our institution between September 2019 and July 2024, we retrospectively analyzed 36 patients who subsequently received ICI maintenance therapy following the initial chemoimmunotherapy treatment. The SII was calculated at the start of the second cycle of the ICI maintenance therapy. Patients were stratified into high (≥ 570) and low (< 570) SII groups. Overall survival (OS) and progression-free survival (PFS) were compared between the groups using the Kaplan-Meier method and log-rank test. Multivariate analysis using the Cox proportional hazards model was performed to identify independent prognostic factors.
    RESULTS: The high SII group exhibited a significantly shorter OS (median 12.1 vs. 24.1 months, P = 0.010) and PFS (median 5.2 vs. 8.1 months, P = 0.026) than those in the low SII group. A multivariate analysis identified SII ≥ 570 as an independent negative prognostic factor for OS (hazard ratio 3.83, 95% confidence interval 1.38-10.6, P = 0.010).
    CONCLUSIONS: Elevated SII in the initial phase of ICI maintenance therapy was associated a with poor prognosis in patients with SCLC, supporting its utility as a prognostic biomarker in this setting. Therefore, prospective validation is required to confirm these findings.
    Keywords:  Immune checkpoint inhibitor; Neutrophil-to-lymphocyte ratio; Prognostic biomarker; Small-cell lung cancer; Systemic immune-inflammation index
    DOI:  https://doi.org/10.1186/s12885-025-13440-5
  5. Bull Cancer. 2025 Jan 03. pii: S0007-4551(24)00469-7. [Epub ahead of print]
       BACKGROUND: Lung adenocarcinoma (LUAD) is the most prevalent histological subtype of lung cancer. Pyroptosis is a programmatic cell death linked to inflammation.
    METHODS: The data information of 541 LUAD samples and 59 normal samples were obtained from TCGA database. The analysis of differentially expressed genes (DEGs) was carried out on LUAD patients. The intersection of integrated PRGs and IRGs with DEGs yielded IPRGs. We utilized univariate Cox regression to determine IPRGs linked to overall survival (OS). Based on their expression levels, unsupervised clustering of LUAD was conducted. Patients were divided into two clusters. Analyses of immunity and drugs were performed in two clusters.
    RESULTS: One hundred and thirty-two IPRGs were linked with OS. Cluster 1 had a longer OS. Two thousand two hundred and fifty-six DEGs were detected in various subtypes. The results of immune analysis showed that most of the immune cells in cluster 2, which had a worse prognosis, had a low degree of infiltration. High Th2 cell infiltration may be related to poor prognosis in LUAD patients. Higher tumor immune dysfunction and exclusion (TIDE) and immunophenotypic scores in Cluster 1 indicated that these patients may have a better response to immunotherapy. There were significant differences in human leukocyte antigen (HLA), immune checkpoints, immunophenoscore (IPS), and TIDE scores in the two subtypes. The mutation frequencies of the top 10 genes in cluster 2 were higher than those in cluster 1. Different subtypes also had distinct sensitivities to different drugs.
    CONCLUSION: IPRGs can be utilized for LUAD subtyping. Different subtypes have varied immune landscapes and immunotherapy responses.
    Keywords:  Gene typing; Immune landscape; Immune-related genes; Lung adenocarcinoma; Pyroptosis-related genes
    DOI:  https://doi.org/10.1016/j.bulcan.2024.11.009
  6. Cancers (Basel). 2024 Dec 12. pii: 4145. [Epub ahead of print]16(24):
      Lung cancer is a deadly disease with the highest rates of mortality. Over recent decades, a better understanding of the biological mechanisms implicated in its pathogenesis has led to the development of targeted therapies and immunotherapy, resulting in improvements in patient outcomes. To better understand lung cancer tumor biology and advance towards precision oncology, a comprehensive tumor profile is necessary. In recent years, novel in situ spatial multiomics approaches have emerged offering a more detailed view of the spatial location of tumor and tumor microenvironment cells, identifying their unique composition and functional status. In this sense, novel multiomics platforms have been developed to evaluate tumor heterogeneity, gene expression, metabolic reprogramming, signaling pathway activation, cell-cell interactions, and immune cell programs. In lung cancer research, several studies have used these spatial technologies to locate cells and associated them with histological features that are relevant to the pathogenesis of lung adenocarcinoma. These advancements may unveil further molecular and immune mechanisms in tumor biology that will lead to the discovery of biomarkers for treatment prediction and prognosis. In this review, we provide an overview of more widely used and emerging pathology-based approaches for spatial immune profiling in lung cancer and how they enhance our understanding of tumor biology and immune response.
    Keywords:  immune profiling; lung carcinoma; spatial cellular analysis
    DOI:  https://doi.org/10.3390/cancers16244145
  7. Int J Gen Med. 2024 ;17 6595-6604
       Purpose: To further identify the clinical impact of metformin on the prognosis of non-small cell lung cancer (NSCLC) with type 2 diabetes who received immunotherapy.
    Methods: Stage IV NSCLC patients with type 2 diabetes receiving the immunotherapy from 2017 to 2021 were retrospectively enrolled and divided into the metformin group or non-metformin group according to the treatment strategy for type 2 diabetes (metformin vs other hypoglycemic medicines). The overall response rate (ORR) was primary endpoint, and overall survival (OS), progression-free survival (PFS) and disease control rate (DCR) were secondary endpoints. These outcomes were compared between two groups.
    Results: A total of 34 patients were eventually enrolled, including 18 patients in the metformin group. No significant differences in the basic characteristics and incidence of adverse events were observed between two groups. In addition, there was no significant difference in ORR (44.4%, 8/18 vs 25.0%, 4/16, P = 0.236) and DCR (77.8%, 14/18 vs 75.0%, 12/16, P > 0.999) between the metformin and non-metformin groups. Kaplan-Meier survival curve (P = 0.039) and Cox regression analysis indicated that the use of metformin was an independent factor for OS (HR: 0.310, 95% CI: 0.113-0.845, P = 0.022), but not for PFS (Cox regression analysis: P = 0.145).
    Conclusion: For NSCLC patients with type 2 diabetes, the combination of metformin and immunotherapy may contribute to OS benefits. However, more high-quality prospective studies with big sample sizes are needed to further clarify the effect of metformin use on the efficacy of immunotherapy in advanced NSCLC patients with diabetes.
    Keywords:  immunotherapy; metformin; non-small cell lung cancer; prognosis
    DOI:  https://doi.org/10.2147/IJGM.S495449