ArticleTranslational lung cancer research2021
One carbon metabolism in human lung cancer.
Article in Translational lung cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 45 citations in OpenAlex.
- Expression of Thymidylate Synthase in Cancer: A Tissue Microarray Study Involving 17,371 Cancers from 136 Tumor Entities.Biomedicines · 2026Article
- MTHFD2: a promising metabolic checkpoint for diseases.Journal of translational medicine · 2026Review
- NADPH-Related Enzymes and Cancer: Facts and Insights Into the Application of Immunohistochemistry.Biochemistry research international · 2026Review
- Multifaceted role of serine hydroxymethyltransferase in health and disease.Molecules and cells · 2025Review
- MTHFD2 marks pemetrexed resistance in pulmonary adenocarcinoma with EGFR wild type.Discover oncology · 2025Article
- Serine synthesis and catabolism in starved lung cancer and primary bronchial epithelial cells.Cancer & metabolism · 2024Article
- Developing technologies and areas of interest in lung cancer screening adjuncts.Journal of thoracic disease · 2024Review
- Constructing a folate metabolism gene signature for predicting prognosis in pulmonary neuroendocrine carcinomas.Journal of Cancer · 2024Article
- Integrative single-cell analysis of LUAD: elucidating immune cell dynamics and prognostic modeling based on exhausted CD8+ T cells.Frontiers in immunology · 2024Article
- Article
- A Systematic Role of Metabolomics, Metabolic Pathways, and Chemical Metabolism in Lung Cancer.Vaccines · 2023Review
- Total coumarins of Pileostegia tomentella induces cell death in SCLC by reprogramming metabolic patterns, possibly through attenuating β-catenin/AMPK/SIRT1.Chinese medicine · 2023Article
- Phosphorylation by IKKβ Promotes the Degradation of HMGCL via NEDD4 in Lung Cancer.International journal of biological sciences · 2023Article
- Regulation and Therapeutic Targeting of MTHFD2 and EZH2 in KRAS-Mutated Human Pulmonary Adenocarcinoma.Metabolites · 2022Article
- Prediction of axillary lymph node metastasis in triple-negative breast cancer by multi-omics analysis and an integrated model.Annals of translational medicine · 2022Article
- Comprehensive analyses of one-carbon metabolism related genes and their association with prognosis, tumor microenvironment, chemotherapy resistance and immunotherapy in lung adenocarcinoma.Frontiers in molecular biosciences · 2022Article
- Arginine Deprivation in SCLC: Mechanisms and Perspectives for Therapy.Lung Cancer (Auckland, N.Z.) · 2022Review
- ATF4/MYC Regulates MTHFD2 to Promote NSCLC Progression by Mediating Redox Homeostasis.Disease markers · 2022Article
- A Cluster of Metabolic-Related Genes Serve as Potential Prognostic Biomarkers for Renal Cell Carcinoma.Frontiers in genetics · 2022Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLung cancer remains the major cause of cancer related death worldwide. The discovery of targeted therapies against activating mutations in genes like EGFR considerably improved the prognosis for a subgroup of patients but still leaves a large part without a targeted therapy. One carbon metabolism (1CM) has been investigated in several cancer entities and its increased activity has been linked to higher tumor aggressiveness and reduced prognosis. In spite of 1CM enzymes role and correlation to cancer cells progression, comprehensive analysis for the diagnostic and functional role of the complete 1CM enzymes in lung cancer has not been conducted so far.
methodsWe investigated the prognostic and functional relevance of five major 1CM factors (MTHFD2, PGDH3, SHMT2, MTHFD1 and TYMS) in the three major subclasses of lung cancer [pulmonary adenocarcinoma (AC), squamous cell lung cancer (SQCLC) and small cell lung cancer (SCLC)]. We analyzed 1CM enzymes expression and clinicopathological correlation in patient derived tissue samples of 103 AC, 183 SQCLC and 37 SCLC patients by immunohistochemistry. Furthermore, the effect of 1CM enzymes expression on lung cancer cell proliferation and the response to chemotherapy was investigated in 15 representative AC, SQCLC and SCLC cell lines.
resultsExpression of MTHFD2 and PGDH3 was significantly correlated to a worse overall survival only in AC patients. Cell proliferation assays resolved that all 1CM enzymes have a significant impact on cell growth in AC cell lines and are partially involved in cell proliferation in SQCLC and SCLC cell lines. In addition, expression of MTHFD2 correlated significantly with an increased pemetrexed chemoresistance.
conclusionsExpression of MTHFD2 significantly reduces the prognosis of AC patients. Furthermore, MTHFD2 expression is crucial for survival of AC cell lines and its expression correlates with resistance against Pemetrexed. As MTHFD2 is almost not expressed in healthy adult tissue, we therefore suggest that the inhibition of MTHFD2 might be a potential therapeutic strategy to surround pemetrexed resistance in AC.
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