Discover. Oncology最新文献

Background: Neoadjuvant chemoimmunotherapy (nCIT) has improved outcomes in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, accessible and reliable biomarkers to predict survival and pathological response remain limited. This study assessed the prognostic and predictive value of the Global Immune-Nutrition Index (GINI), cytokeratin-19 fragment (CYFRA 21 - 1), fibrinogen-albumin ratio index (FARI), and a composite score combining these markers-the GINI-CYFRA 21 - 1-FARI (GCF) score.

Methods: A retrospective analysis was conducted on 138 LA-ESCC patients who received nCIT followed by radical esophagectomy between 2021 and 2023. Optimal cut-off values for GINI, CYFRA 21 - 1, and FARI were determined using X-tile software. The composite GCF score was developed accordingly. Associations with disease-free survival (DFS) were evaluated using Kaplan-Meier analysis and multivariable Cox regression. Predictive performance was assessed via time-dependent ROC curves. Tumor regression grade (TRG) was analyzed using logistic regression, and a nomogram was constructed to predict pathological response.

Results: Elevated levels of GINI (median DFS: 20 vs. not estimable [NE] months; p = 0.001), CYFRA 21 - 1 (19 vs. NE months; p < 0.001), FARI (11 vs. 26 months; p < 0.001), and higher GCF scores (0 vs. 1 vs. ≥2: 18 vs. 22 vs. NE months; p < 0.001) were associated with worse DFS. The GCF score was independently predictive of DFS (low vs. high: HR = 0.264; p = 0.028) and demonstrated consistent discriminative capacity. For pathological response, the GCF score showed predictive value for TRG (AUC = 0.625; p = 0.004) and was independently associated with poor TRG (high vs. low: OR = 2.170; p = 0.048). A nomogram incorporating the GCF score outperformed models excluding it (AUC: 0.787 vs. 0.662; p < 0.05).

Conclusions: The GCF score-a composite of GINI, CYFRA 21 - 1, and FARI-independently predicts DFS and pathological response following nCIT and surgery in LA-ESCC, and may hold potential as a practical, blood-based biomarker. Its integration significantly enhances predictive model performance and may aid in individualized patient risk stratification.

Background: Lung adenocarcinoma (LUAD) remains a leading cause of cancer mortality worldwide. Although oxidative phosphorylation (OXPHOS) has been linked to tumor progression, its prognostic significance and underlying mechanisms in LUAD remain unclear.

Methods: RNA-seq data from TCGA were used as the discovery cohort, and multiple GEO datasets were used for independent validation. OXPHOS-related genes were obtained from MitoCarta3.0. Prognostic biomarkers were selected by LASSO-Cox regression. Immune cell infiltration was estimated using CIBERSORT and ssGSEA. Single-cell RNA-seq data were analyzed to examine biomarker expression, pathway enrichment, and cell-cell communication.

Results: Thirteen OXPHOS-associated genes were used to construct a prognostic model with robust predictive performance. Model performance was validated across independent cohorts and demonstrated reliable prognostic value. Higher risk scores correlated with poorer overall survival and reduced immune infiltration. UQCC3⁺ and RAB5IF⁺ epithelial cells were enriched in E2F target and G2M checkpoint pathways and showed enhanced interactions via TGF-β and Galectin signaling.

Conclusions: We present an OXPHOS-based prognostic model for LUAD. OXPHOS reprogramming, particularly involving UQCC3 and RAB5IF in epithelial cells, may promote malignant proliferation and immunosuppression. These findings provide novel prognostic biomarkers and potential therapeutic targets, which may support personalized treatment strategies and guide future translational studies.