Bioinformatics analysis of ALDOA expression in non-small cell lung cancer and its impact on prognosis and TME
10.3760/cma.j.cn115355-20241231-00604
- VernacularTitle:ALDOA在非小细胞肺癌中的表达及其对预后和TME影响的生物信息学分析
- Author:
Qiu LI
1
;
Jiashun CAO
Author Information
1. 清华大学北京清华长庚医院科研部，北京 102218
- Publication Type:Journal Article
- Keywords:
Carcinoma, non-small-cell lung;
Fructose-bisphosphate aldolase;
Tumor microenvironment;
Prognosis;
Immunity
- From:
Cancer Research and Clinic
2025;37(10):752-759
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the gene expression level of fructose-bisphosphate aldolase A (ALDOA) in non-small cell lung cancer (NSCLC) tissues and the effect of ALDOA on NSCLC prognosis and immune cell infiltration in tumor microenvironment (TME).Methods:The clinical data of patients with lung adenocarcinoma and squamous cell carcinoma, the data of corresponding gene in tumor tissues and corresponding normal lung tissues in The Cancer Genome Atlas (TCGA) database, and the data of healthy population in the Genotype Tissue Expression (GTEx) database were collected in June 2023. Gene Expression Profile Interaction Analysis (GEPIA) 2.0 online tool was used to explore the expression differences of ALDOA at transcription level in NSCLC tissues and normal lung tissues, as well as NSCLC tissues of different stages; the expression of ALDOA was obtained through immunohistochemical staining in different pathological types of NSCLC and normal lung tissues from the Human Protein Atlas (HPA) database; the survival of patients with high and low expression of ALDOA in NSCLC tissues in TCGA database was evaluated by plotting Kaplan-Meier survival curves (differentiated by the median expression of ALDOA at transcription level in NSCLC samples), and log-rank test was used for comparing survival between groups. Using the Tumor Immune Estimation Resource (TIMER) 2.0 database, the CIBERSORT algorithm was applied to evaluate the correlation between ALDOA expression and immune cell infiltration levels in NSCLC tissues from the TCGA database. Further analysis of the correlation between ALDOA expression levels and programmed death receptor ligand 1 (PD-L1), matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF), and various inflammatory factors in NSCLC tissues was conducted using the GEPIA 2.0 online tool to evaluate the impact of ALDOA expression levels on the tumor immune microenvironment.Results:The expression of ALDOA at transcription level in lung adenocarcinoma (483 cases) and lung squamous cell carcinoma (486 cases) tissues were higher than those in corresponding normal lung tissues (347 and 338 cases, respectively), and the differences were statistically significant (all P < 0.01). There was a statistically significant difference in the expression of ALDOA at transcription level among TNM stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ NSCLC tissues ( F = 4.55, P = 0.004), and the expression level of ALDOA gradually increased with the increase of stage. In the HPA database, ALDOA protein stained by immunohistochemistry showed mild to moderate staining in normal lung tissues, while it showed severe staining in lung adenocarcinoma and squamous cell carcinoma tissue samples. Kaplan-Meier survival analysis showed that the overall survival of lung adenocarcinoma patients (239 cases) with high ALDOA expression was worse than that of patients with low ALDOA expression (239 cases) ( P < 0.001), and there was no statistically significant difference in disease-free survival between the two groups ( P = 0.140). There was no statistically significant difference in overall survival and disease-free survival between patients with high expression (241 cases) and low expression (241 cases) of ALDOA in lung squamous cell carcinoma (both P > 0.05). TIMER 2.0 database analysis shows that in lung adenocarcinoma, the expression of ALDOA at transcription level was negatively correlated with the levels of activated mast cells ( Rho = -0.209) and memory B cells ( Rho = -0.133), and positively correlated with the levels of resting mast cells ( Rho = 0.210) and resting natural killer cells ( Rho = 0.110), with statistically significant differences (all P < 0.05). In lung squamous cell carcinoma, the expression of ALDOA at transcription level was negatively correlated with the levels of activated mast cells ( Rho = -0.105), memory B cells ( Rho = -0.213) and CD8 + T cells ( Rho = -0.148), and positively correlated with the levels of resting mast cells ( Rho = 0.173), plasma B cells ( Rho = 0.174) and resting natural killer cells ( Rho = 0.136), with statistically significant differences (all P < 0.05). In NSCLC tissues, the expression of ALDOA at transcription level was negatively correlated with PD-L1 ( R = -0.11), interleukin (IL)-2 ( R = -0.31), IL-4 ( R = -0.14), IL-5 ( R = -0.10), IL-6 ( R = -0.12), and IL-10 ( R = -0.24) levels (all P < 0.001), positively correlated with MMP-9 ( R = 0.11) and VEGF ( R = 0.18) levels (both P < 0.001), and positively correlated with IL-9 ( R = 0.11) and VEGF ( R = 0.18) levels (both P < 0.001), but it was not correlated with IL-17 level ( R = -0.02, P = 0.540). Conclusions:The expression level of ALDOA is elevated in NSCLC tissues, and high ALDOA level in lung adenocarcinoma may indicate poor survival of patients. ALDOA may affect the levels of immune cell infiltration, tumor markers and inflammatory factors in TME, and it may be a potential biomarker for prognosis.
