bims-necame 2025-06-08 papers

Issue of 2025–06–08
two papers selected by
Grigor Varuzhanyan, UCLA

Front Mol Biosci. 2025 ;12 1592888

Metabolic reprogramming signature predicts prognosis and immune landscape in small cell lung cancer: MOCS2 validation and implications for personalized therapy.

Junyan Wang, Panpan Sun, Fan Zhang, Yu Xu, Shenghu Guo.

Introduction: Small cell lung cancer (SCLC) remains a leading cause of cancer mortality worldwide, characterized by rapid progression and poor clinical outcomes, and the function of metabolic reprogramming remains unclear in SCLC.
Methods: We performed multi-omics analysis using public SCLC datasets, analyzing single-cell RNA sequencing to identify metabolic reprogramming patterns between chemotherapy-resistant and sensitive samples. Bulk RNA sequencing from GSE60052 and cBioportal cohorts was used to identify metabolism-related gene modules through WGCNA and develop a Gradient Boosting Machine prognostic model. Functional validation of MOCS2, the top-ranked gene in our model, was conducted through siRNA knockdown experiments in SCLC cell lines.
Results: Single-cell analysis revealed distinct metabolic reprogramming patterns between chemotherapy-resistant and sensitive samples. WGCNA identified a turquoise module strongly correlated with metabolic reprogramming (cor = 0.56, P < 0.005). The GBM-based prognostic model demonstrated excellent performance (C-index = 0.915) with MOCS2, USP39, SMYD2, GFPT1, and PRKRIR identified as the most important variables. Kaplan-Meier analysis confirmed significant survival differences between high-risk and low-risk groups in both validation cohorts (P < 0.001). In vitro experiments showed that MOCS2 knockdown significantly reduced SCLC cell proliferation, colony formation, and migration capabilities (all P < 0.01), confirming its crucial role in regulating SCLC cell biology. Immunological characterization revealed distinct immune landscapes between risk groups, and drug sensitivity analysis identified five compounds with significantly different response profiles between risk groups.
Conclusion: Our study established a robust metabolism-based prognostic model for SCLC that effectively stratifies patients into risk groups with distinct survival outcomes, immune profiles, and drug sensitivity patterns. Functional validation experiments confirmed MOCS2 as an important regulator of SCLC cell proliferation and migration, providing valuable insights for treatment selection and prognosis prediction in SCLC.

Keywords: drug sensitivity; immune microenvironment; metabolic reprogramming; prognosis; small cell lung cancer

DOI: https://doi.org/10.3389/fmolb.2025.1592888

Cancer Res. 2025 Jun 06.

A spotlight on oxidative metabolism in oncogenic transformation and cell competition.

Yogaspoorthi J Subramaniam, Eugenia Piddini.

Normal tissues actively employ a phenomenon called cell competition to drive the elimination and replacement of less fit loser cells by fitter winner cells. This quality control mechanism promotes tissues health, by favouring the selective expansion of fitter cells. Indeed, through cell competition, many mutant cells are eliminated from tissues by fitter normal cells. However, some oncogenic mutations can turn cells into super-competitors that outcompete normal cells, promoting tumorigenic growth and metastasis. Several cellular stresses have been associated with the loser status such as oxidative stress, DNA damage responses, unfolded protein response and mitochondrial dysfunction. By affecting these pathways, metabolism and dietary choices can regulate cellular fitness and cell competition. However, how these pathways affect competitive interactions in vivo, during the early establishment of mutant clones, is relatively little understood. Recent work from Hemalatha and colleagues introduces real-time fluorescence ratio metric imaging of NAD(P)H and FAD, to investigate cellular redox status - live and over time, at single cell level - as cells compete in the mouse epidermis. Their work demonstrates that redox status changes dynamically during competition between cell carrying oncogenic mutations. It further shows that drugs that modulate mitochondrial metabolism and cellular redox are strong modulators of cell competition. The introduction of live redox imaging will prove a powerful tool to further dissect how metabolic states affect cell competition in normal physiology and in tumorigenesis.

DOI: https://doi.org/10.1158/0008-5472.CAN-25-2374