A method for the identification of lactate metabolism-related prognostic biomarkers and its validations in non-small cell lung cancer

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 17, 2025

Lactate metabolism (LM) plays a crucial role in tumor progression and therapy resistance non-small cell lung cancer (NSCLC). Several methods had been developed for NSCLC prognosis prediction based on lactate metabolism-related information. The existing the construction of models are mostly single such as linear models, SVM, decision trees. Prognosis biomarkers this kind often have limited prognostic performance. In study, we proposed novel methodology constructing model identifying lactate-related NSCLC. We first screened malignant genes from scRNA-Seq data cells. Cox elastic-net regression combined with genetic algorithm (GA-EnCox) to predict optimize selection key biomarkers. identified five LM-related (LYPD3, KRT8, CCT6A, PSMB7, HMGA1) that significantly correlated patient LUAD cohorts. constructed these outperformed other currently popular across multiple datasets, demonstrating stable predictive capability. Survival analysis bulk RNA-Seq demonstrated low-risk group better overall survival compared high-risk group. Further revealed risk might be associated monocyte lineages macrophages DC's infiltration may indicate therapeutic responses immune checkpoint inhibitors patients. More importantly, validated HMGA1 KRT8 at protein level their association histologic grades, stages, clinical outcomes consistently treated in-house Finally, experimentally one biomarkers, HMGA1, confirming its promoting phenotypes This study provides valuable insights into impact outcomes, it was expected provide important reference value assessment personalized treatment

Language: Английский

---

Transcriptome-based insights into the role of cancer-associated fibroblasts in lung adenocarcinoma prognosis and therapy

Computer Methods in Biomechanics & Biomedical Engineering, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 16

Published: March 12, 2025

Cancer-associated fibroblasts (CAFs) are related to drug resistance and prognosis of tumor patients. This study aimed investigate the relationship between treatment response in patients with CAF lung adenocarcinoma (LUAD). The data pertaining LUAD were obtained from Cancer Genome Atlas-LUAD GSE68465 datasets. Four different algorithms used quantify infiltration stromal scores. Weighted gene network co-expression analysis was identify CAF-related modules hub genes. Univariate Cox regression analysis, least absolute shrinkage selection operator multivariate construct signatures, whose ability predict verified by individual signature eight genes constructed, score calculated. high scores significantly worse than that low an independent risk factor for prognosis. Patients sensitive some chemotherapy drugs, most cases, they non-responsive immunotherapy. Eight-gene may patient evaluate clinical responses immunotherapy, enabling individualized

Language: Английский

---

Molecular signatures bidirectionally link myocardial infarction and lung cancer

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: April 9, 2025

Myocardial Infarction (MI) and lung cancers are major contributors to mortality worldwide. While seemingly diverse, the two share common risk factors, such as smoking hypertension. There is a pressing need identify bidirectional molecular signatures that link MI cancer, in order improve clinical outcomes for patients. In this study, we identified differentially expressed genes between cancer. Specifically, 1,496 upregulated 1,482 downregulated datasets. By focusing on 1,000 most Lung Adenocarcinoma (LUAD) Squamous Cell Carcinoma (LUSC), 35 across MI, LUAD, LUSC. Functional enrichment analysis revealed shared biological processes, "inflammatory response" "cell differentiation." The Cox proportional hazards model demonstrated significant association overall survival cancer patients, well with history these addition, machine learning based expression of distinguished patients from controls, achieving an AUROC 0.72 AUPRC 0.86. Finally, drug repurposing analysis, proposed FDA-approved drugs potentially targeting novel therapeutic options co-occurring conditions Overall, our findings highlight similarities makeup MI.

Language: Английский

---

A tumour necrosis factor-α responsive cryptic promoter drives overexpression of the human endogenous retrovirus ERVK-7

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108568 - 108568

Published: April 1, 2025

Endogenous retroviruses (ERVs) shape human genome functionality and influence disease pathogenesis, including cancer. ERVK-7, a significant ERV, acts as an immune modulator prognostic marker in lung adenocarcinoma (LUAD). Although ERVK-7 overexpression has been linked to the amplification of 1q22 locus approximately 10% LUAD cases, it predominantly arises from alternative regulatory mechanisms. Our findings indicate that canonical 5' long terminal repeat (LTR) is methylated inactive, necessitating use upstream promoters. We identified two novel transcripts, ERVK-7.long ERVK-7.short, arising distinct promoters located 2.8 kb 13.8 5'LTR respectively. overexpressed LUAD. Through comprehensive epigenetic mapping single-cell transcriptomics, we demonstrate activation predetermined by cell lineage, specifically small airway epithelial cells (SAECs), where its promoter displays tumor-specific H3K4me3 modifications. Single-cell RNA sequencing further reveals enrichment tumor alveolar type 2 cells, underscoring cell-type-specific origin. Additionally, inflammatory signaling significantly influences expression; TNF-α enhances ERVK-7.long, while interferon preferentially augments ERVK-7.short differential recruitment NF-κB/RELA IRF their respective This regulation clarifies elevated expression compared squamous carcinoma (LUSC). study elucidates complex mechanisms governing proposes these transcripts potential biomarkers therapeutic targets, offering new avenues improve patient outcomes.

Language: Английский

---

NOC4L serves as a novel prognostic marker and therapeutic target for lung adenocarcinoma

European Journal of Medicinal Chemistry Reports, Journal Year: 2025, Volume and Issue: unknown, P. 100274 - 100274

Published: May 1, 2025

Language: Английский

---

PIK3CA Mutations and Co-Mutations in Operated Non-Small Cell Lung Carcinoma

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(23), P. 7472 - 7472

Published: Dec. 8, 2024

Understanding

Language: Английский

---