PTX3 as a diagnostic and prognostic biomarker in lung adenocarcinoma: a comprehensive analysis

Abstract

Background: Lung cancer remains a leading global cause of mortality, with lung adenocarcinoma (LUAD) as the predominant histological subtype. Current serum biomarkers like carcinoembryonic antigen (CEA) lack specificity, necessitating novel diagnostic targets. Pentraxin 3 (PTX3), a homo-multimeric protein downregulated in malignancies, was evaluated for its diagnostic and prognostic roles in LUAD.

Methods: PTX3 expression was analyzed using TCGA/GEO datasets and clinical serum samples (97 LUAD vs. 40 controls). Diagnostic utility was assessed via ROC curves for PTX3, CEACAM5, and their combination. Prognostic value was determined by Kaplan-Meier and Cox regression. PTX3-associated differentially expressed genes (DEGs) were explored through functional enrichment, tumor microenvironment (TME) analysis, and drug sensitivity profiling.

Result: The TCGA and GEO datasets revealed that PTX3 mRNA expression was significantly downregulated in LUAD, and the AUC values with PTX3 were > 0.7. Detection of CEACAM5 and PTX3 combined can improve diagnostic accuracy, and patients with high PTX3 level have shorter overall survival. Multivariate Cox analysis revealed that PTX3 is an independent predictor of overall survival. The result of ELISA further confirmed the low level of PTX3 protein. PTX3 is important in the functional analysis and TME of lung adenocarcinoma. In addition, the sensitivity of tumor cells to anti-cancer drugs is significantly correlated with the expression of PTX3.

Conclusion: PTX3 emerges as a dual biomarker for LUAD diagnosis and prognosis, with mechanistic ties to TME remodeling and therapeutic resistance, highlighting its potential for clinical translation.

Keywords: Diagnosis; Immune; Lung adenocarcinoma; PTX3.

Fig. 1

PTX3 mRNA expression in pan-cancer and LUAD. A PTX3 mRNA expression in pan-cancer. B PTX3 mRNA expression in TCGA. C, D PTX3 mRNA expression in GSE31210 (C) and GSE68571 (D). (E–J) Correlations between PTX3 mRNA expression and clinical features in LUAD patients according to Gender (E), Age (G), Clinical stage (H), N stage (I), M stage (F), and T classification (J). Statistical significance was determined by Mann-Whitney U test. Significance thresholds: ns, P > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001

Fig. 2

PTX3 mRNA expression ROC curve in TCGA and GEO LUAD patients. A PTX3, CEACAM5, and PTX3 combined CEACAM5 mRNA expression ROC curve in TCGA tumor and normal tissues. B PTX3, CEACAM5, and PTX3 combined CEACAM5 mRNA expression ROC curve in GSE68571 tumor and normal tissues. C PTX3, CEACAM5, and PTX3 combined CEACAM5 mRNA expression ROC curve in GSE31210 tumor and normal tissues. Statistical Analysis: AUC comparisons were performed using DeLong’s test

Fig. 3

Prognostic correlation analysis of PTX3 in LUAD in TCGA cohort. A Kaplan-Meier analysis for LUAD patients’ overall survival (Log-Rank test). B Time-dependent ROC curves at 3, 5- and 10- years. C Kaplan-Meier analysis of overall survival in four different subgroups of LUAD patients (Log-Rank test). D A forest plot of univariate Cox analysis risk factors for LUAD patients (Wald test). E A forest plot of multivariate Cox analysis risk factors for LUAD patients (Wald test)

Fig. 4

Identification of PTX3-related genes. A DEGs with high and low PTX3 expression are displayed in a heatmap. B These differentially expressed genes’ PPI network. C Correlation between PTX3 expression and 11 genes

Fig. 5

Correlations between PTX3 expression and sensitivity to drugs. Comparison of IC50 value for Oxaliplatin (A), Dasatinib (B), KRAS inhibitor(G12C)-12 (C), Nilotinib (D), Gefitinib (E), and Lapatinib (F) respectively. Statistical significance was determined by Mann-Whitney U test. Significance thresholds: ns, P > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001

Fig. 6

PTX3 and CEA serum protein level in clinical samples. A PTX3 protein level in the serum of tumor patients and healthy controls. B CEA level in the serum of tumor patients and healthy controls. C ROC curves of PTX3, CEA, and their combination for distinguishing tumor patients from healthy controls. D–I Correlation between PTX3 protein level and clinical features in LUAD patients according to T classification (H), M stage (F), N stage (G), clinical stage (I), Age (D), and Gender (E). Statistical significance was determined by Mann-Whitney U test. Significance thresholds: ns, P > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001