Transl Lung Cancer Res. 2025 Sep 30;14(9):3645-3658. doi: 10.21037/tlcr-2025-603. Epub 2025 Sep 25.

ABSTRACT

BACKGROUND: Lung cancer poses a major public health challenge, accounting for the highest cancer-related mortality worldwide. This study aimed to identify non-invasive biomarkers for the early detection of non-small cell lung cancer (NSCLC) risk.

METHODS: We randomly selected 150 incident NSCLC cases during follow-up from the Korean Cancer Prevention Study-II. Controls (n=150) were matched to cases by age, gender, and the time of blood collection. Non-targeted metabolite screening by ultra-high-performance liquid chromatography (UHPLC)/mass spectrometry (MS) was conducted on the pre-diagnostic biological samples. The 11 reported lung cancer-associated single-nucleotide polymorphisms (SNPs) in Koreans were extracted from DNA genotyping data of the study population. Metabolite markers related to NSCLC risk were identified through clustering using hierarchical density-based spatial clustering of applications with noise. The associations between smoking, dietary factors, and NSCLC were also examined.

RESULTS: Six discriminative serum metabolites were identified as having an association with NSCLC incidence. Notably, the relationship between specific metabolite levels and NSCLC risk differed by rs7086803 genotype. Smoking status and occupational exposures appear to influence specific metabolite profiles, while dietary vegetable intake may modulate the risk of NSCLC among smokers.

CONCLUSIONS: The meaningful biomarkers revealed in the current research could be used to enhance the predictive ability for NSCLC risk. Furthermore, we suggest that the protective role of dietary vegetables against NSCLC may be attenuated or absent in smokers.

PMID:41133005 | PMC:PMC12541849 | DOI:10.21037/tlcr-2025-603

OMICS. 2025 Oct 16. doi: 10.1177/15578100251387518. Online ahead of print.

ABSTRACT

Lung adenocarcinoma (LUAD) remains the most common subtype of lung cancer, characterized by high heterogeneity and poor survival outcomes. Although transcriptomic and metabolomic alterations have been individually studied, integrated multi-omics analyses are needed to uncover the convergent pathways that drive tumor progression. Differentially expressed genes (DEGs) were identified from the GSE229253 transcriptomic dataset comprising LUAD tumor and adjacent normal tissues, while significantly altered metabolites were obtained from the Lung Cancer Metabolome Database. The top 10 DEGs and metabolites were analyzed using the search tool for interacting chemicals (STITCH) to construct gene-metabolite networks, and Integrated Molecular Pathway Level Analysis (IMPaLA) was employed for integrated pathway enrichment to identify overlapping molecular processes. Transcriptomic profiling revealed 973 DEGs (410 upregulated and 563 downregulated), and metabolomic analysis identified significant alterations in metabolites linked to redox balance, amino acid derivatives, and nucleotide metabolism. Integration through STITCH generated a network of 16 nodes and 9 edges, highlighting gene-metabolite associations of probable biological relevance. Joint pathway enrichment analysis using IMPaLA consistently identified glycosylation-related pathways, particularly O-linked glycosylation of mucins, as major axes of convergence between transcriptomic and metabolomic alterations in LUAD (joint p = 0.00129-0.00434). Several genes (B3GNT6, FEZF1-AS1, and LCAL1) and metabolites (isoleucylleucine, leucylleucine, and isoleucylvaline) are probable novel candidates, warranting further investigation. These findings provide systems-level evidence that aberrant glycosylation is likely a central hallmark of LUAD, underscore the potential of glycosylation pathways as biomarkers and therapeutic targets, and demonstrate the utility of cross-omics approaches to unpack the molecular complexity of lung cancer.

PMID:41103242 | DOI:10.1177/15578100251387518

In Silico Pharmacol. 2025 Oct 17;13(3):154. doi: 10.1007/s40203-025-00440-3. eCollection 2025.

ABSTRACT

Breast, ovarian, lung, cervical, and colorectal cancers are among the most prevalent malignancies affecting women worldwide. This study aimed to elucidate the common molecular mechanisms of tumorigenesis and identify potential biomarkers using an integrative bioinformatics and network-based approach. Integrative profiling of five microarray datasets identified 66 differentially expressed genes (DEGs) that are common across five cancer types. Gene ontology and KEGG pathway analyses of common DEGs were performed using the DAVID database. The cell cycle processes were the most enriched functions, and oocyte meiosis, oocyte maturation, the p53 signaling pathway, cancer pathways, and cellular senescence were the most important pathways identified. Protein-protein interaction (PPI) networks for the DEGs were constructed using the STRING database, and the resulting networks were visualized in Cytoscape. Through PPI network analysis, ten hub genes were identified, and subsequent survival analysis confirmed that CHEK1, DLGAP5, CCNB2, and CCNA2 are significantly associated with poor patient survivability, establishing them as common biomarkers across multiple cancer types. Subsequently, ten transcription factors (TFs) and ten post-transcriptional regulators were identified through the assessment of regulatory networks involving TFs-DEGs and miRNAs-DEGs. Finally, drug-gene association analysis from the GSCA library was used to anticipate drug-like compounds using the drug repurposing approach. Overall, this comprehensive investigation holds promise for future in vitro and in vivo studies, offering a molecular foundation for the diagnosis, prognosis, and treatment of malignant cancers.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-025-00440-3.

PMID:41113171 | PMC:PMC12534660 | DOI:10.1007/s40203-025-00440-3