bims-metorg 2026-02-15 papers

Issue of 2026–02–15
three papers selected by
Bruna Martins Garcia, CABIMER

Cancers (Basel). 2026 Feb 03. pii: 501. [Epub ahead of print]18(3):

Differential Metastatic Patterns and Prognostic Value of Systemic Inflammation Scores in Anaplastic Lymphoma Kinase Rearranged Versus Anaplastic Lymphoma Kinase Negative Non-Small Cell Lung Cancer.

Melek Özdemir, Gamze Gököz Doğu, Burcu Yapar Taşköylü, Arzu Yaren, Serkan Değirmencioğlu, Atike Gökçen Demiray, Ferda Bir, Bensu Selbest Altay, Burçin Çakan Demirel, Tolga Doğan, Semra Taş, Taliha Güçlü Kantar, Ömer Acar.

Background: Non-small cell lung cancer (NSCLC) is the most prevalent form of malignancy and the leading cause of cancer-related fatalities. In clinical practice, metastatic sites are identified on a case-by-case basis. ALK rearrangements are detected in 3-5% of NSCLC cases and are known to have a tendency (tropism) to metastasize to the brain. Methods: Data from 81 ALK-positive and 91 ALK-negative metastatic NSCLC patients were retrospectively analyzed. Systemic markers, including HALP score, NLR, PLR, LMR, and LDH, were calculated from blood tests at the time of metastasis. Optimal cut-off values were determined using ROC analysis. Survival outcomes and prognostic factors were assessed using Kaplan-Meier and Cox regression analyses. Results: ALK-positive patients were significantly associated with female gender (p = 0.002), non-smoking status (p = 0.001), adenocarcinoma histology (p = 0.001), and a higher incidence of brain metastases (p = 0.001). In univariate analysis, age, time to metastasis, liver metastasis, and NLR were prognostic for survival. Crucially, multivariate analysis identified liver metastasis as an independent predictor of poor prognosis (HR = 1.618; 95% CI: 1.050-2.494; p = 0.029), indicating a 61.8% increased risk of death or progression. While inflammation markers (NLR, HALP, PLR, LMR) did not predict metastasis to specific sites, elevated LDH levels were significantly associated with liver metastasis (p = 0.007). Conclusion: ALK-positive NSCLC demonstrates a marked CNS tropism; however, liver metastasis remains a more critical adverse prognostic factor than brain metastasis in real-world settings. While routine inflammation markers showed limited utility in predicting site-specific metastasis, LDH levels correlated significantly with liver involvement. Aggressive management strategies are warranted for ALK-positive patients presenting with liver metastases.

Keywords: ALK rearrangement; brain metastasis; liver metastasis; non-small cell lung cancer; overall survival; systemic inflammation

DOI: https://doi.org/10.3390/cancers18030501

Bio Protoc. 2026 Feb 05. 16(3): e5586

The Generation of Tissue-Specific ECM Hydrogels From Melanoma and Associated Organs to Study Cancer Biology.

Yuval Mogilevsky, Chen Sharon-Yagol, Bar Manobla, Shahaf Saad, Ziv Raviv, Yuval Shaked.

The extracellular matrix (ECM) critically shapes melanoma progression and therapeutic response, yet commonly used matrices such as Matrigel fail to capture tissue- and disease-specific ECM properties. This protocol provides a streamlined and scalable method for generating murine, tissue-specific ECM hydrogels from skin, lung, and melanoma tumors, therefore overcoming the restricted materials of mouse-derived ECM. The workflow integrates tissue-tailored decellularization, lyophilization, mechanical fragmentation, pepsin digestion, and physiological polymerization to produce hydrogels that reliably preserve fibrillar collagen architecture and organ-specific ECM cues. Decellularization efficiency and ECM integrity are validated by DNA quantification, H&E staining, and Picrosirius Red staining analysis. These hydrogels provide a species- and tissue-matched platform for studying melanoma-ECM-immune interactions, pre-metastatic niche features, and therapy-induced ECM remodeling. Overall, this protocol offers a reproducible and physiologically relevant ECM model that expands experimental capabilities for melanoma biology and treatment-resistance research and that can be easily extended to other tumors and tissues. Key features • A miniaturized, tissue-specific workflow for generating ECM hydrogels from small murine skin, lung, and melanoma tissues, overcoming size limitations of existing protocols. • Preservation of native ECM architecture using tailored decellularization steps validated by DNA quantification, H&E, and Picrosirius Red staining. • A standardized digestion-gelation process optimized for heterogeneous and lipid-rich murine tissues, enabling reproducible hydrogel formation at defined ECM concentrations. • A physiologically relevant platform capturing melanoma- and organ-specific ECM cues for studying ECM-tumor-immune interactions and therapy-induced remodeling.

Keywords: Collagen; Decellularization; Extracellular matrix (ECM); Hydrogel; Melanoma; Tumor microenvironment

DOI: https://doi.org/10.21769/BioProtoc.5586

Discov Oncol. 2026 Feb 12.

Integrated analysis of glutamine metabolism and immune microenvironment identifies GOT2 as a prognostic gene in head and neck squamous cell carcinoma.

Xikong Pan, Tingbo Ye, Jianjun Liu, Xucai Zheng.

Glutamine metabolism plays a key role in cancer initiation and progression. This study aims to explore the independent and interactive roles of glutamine metabolism-related genes and immune characteristic in head and neck squamous cell carcinoma (HNSCC). Clinical and gene expression data from HNSCC patients were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA). A comprehensive evaluation of 21 glutamine metabolism-related genes in HNSCC tissues was conducted. A risk model based on glutamine metabolism-related genes was constructed using Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. The association between glutamine metabolism-related genes and immune infiltration was assessed using the Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) method. The expression levels of the hub gene were verified in vitro models. Four glutamine metabolism-related genes (GOT2, FAH, LAT, and SLC7A11) were identified for constructing a risk score model for HNSCC patients. High expression levels of GOT2 were identified as a poor prognostic factor in HNSCC, as demonstrated by Kaplan-Meier analysis (HR:1.006, p < 0.001). Patients with a low-risk score exhibited higher ESTIMATE scores and Immune Scores compared to those with a high-risk score. GOT2 emerged as a hub gene associated with the survival of HNSCC patients. In vitro functional experiments demonstrated that downregulation of GOT2 expression suppresses proliferation, invasion, and metastasis. In conclusions, we developed and validated a prognostic risk scoring system based on four glutamine metabolism-associated genes, which demonstrated robust predictive capacity for clinical outcomes and immune infiltration patterns in HNSCC. Mechanistically, GOT2 emerged as a central regulator interfacing with the immunosuppressive tumor microenvironment, potentially driving oncogenesis through dual metabolic-immune reprogramming. These findings highlight GOT2 as a novel therapeutic target, offering a promising strategy to overcome immunotherapy resistance in HNSCC.

Keywords: GOT2; Glutamine metabolism; Head and neck squamous cell carcinoma; Immunotherapy

DOI: https://doi.org/10.1007/s12672-026-04485-4