PBX3 as a biomarker for the early diagnosis and prediction of prognosis of glioma

Abstract

Background: Increasing evidence have elucidated that PBX3 played a crucial role in cancer initiation and progression. PBX3 was differentially expressed in many cancer types. However, PBX3 potential involvement in gliomas remains to be explored.

Methods: The expression level of PBX3 in glioma tissues and glioma cells, and its correlation with clinical features were analyzed by data from TCGA, GEPIA, CGGA and CCLE. Univariable survival and Multivariate Cox analysis was used to compare several clinical characteristics with survival. We also analyzed the correlation between PBX3 expression level and survival outcome and survival time of LGG and GBM patients by using linear regression equation. GSEA was used to generate an ordered list of all genes related to PBX3 expression and screening of genes co-expressed with PBX3 mRNA by "limma" package.

Results: The results showed that PBX3 was highly expressed in gliomas and its expression increased with the increase of malignancy. Survival analysis found that PBX3 is more valuable in predicting the OS and PFI of LGG patients than that of GBM. For further study, TCGA and CGGA data were downloaded for univariate Cox analysis and multivariate Cox analysis which showed that the expression of PBX3 was independent influencing factors for poor prognosis of LGG patients. Meanwhile, Receiver operating characteristic (ROC) curve showed that PBX3 was a predictor of overall survival rate and progression-free survival rate of LGG. Linear regression model analysis indicated that the higher expression of PBX3 the higher the risk of death of LGG patients, and the higher expression of PBX3 the higher the risk of disease progression of LGG patients. Next, TCGA data were downloaded for GSEA and Co-expression analyses, which was performed to study the function of PBX3.

Conclusion: PBX3 may be involved in the occurrence and development of glioma, and has potential reference value for the early diagnosis and prediction of prognosis of glioma.

Fig 1. Expression level of PBX3 in normal brain, glioma tissues and glioma cells by analyzing data from TCGA, GTEx, GEPIA and CCLE databases.

(A-C) Expression level of PBX3 in full-grade gliomas, LGG and GBM in comparison with the normal brain tissues according to TCGA and GTEx. (D) Expression level of PBX3 in LGG and GBM in comparison with the normal brain tissues according to GEPIA. (E) and (F) The expression level of PBX3 between LGG and GBM according to TCGA and CGGA databases. (G) and (H) The expression level of PBX3 in histological types of gliomas according to TCGA and CGGA databases. (I) The expression level of PBX3 in glioma cell lines according to CCLE databases.

Fig 2. Correlation analysis between PBX3 differential expression and clinical features according to TCGA and CGGA.

A, histologic-grade by TCGA; B, histologic-grade by CGGA; C, sample type by TCGA; D, sample type by CGGA; E, IDH-mutant by TCGA; F, IDH-mutant by CGGA; G, Age by TCGA; H, Age by CGGA; (I and J), cancer-status and karnofsky performance score by TCGA; K, 1p19q-codeletion by CGGA.

Fig 3. Relationship between PBX3 expression and OS of patients with glioma.

(A and B), full-grade gliomas according to TCGA and CGGA databases;(C-E), LGG according to TCGA, CGGA and GEPIA databases;(F-H), GBM according to TCGA, CGGA and GEPIA databases.

Fig 4. Relationship between PBX3 expression and PFI of patients with glioma.

(A), full-grade gliomas according to TCGA databases;(B and C), LGG according to TCGA and GEPIA databases;(D and E), GBM according to TCGA and GEPIA databases.

Fig 5. ROC curve analysis of the predictive efficacy of PBX3 mRNA on 1 -, 3-and 5-year overall survival rate and progression-free survival rate of LGG.

(A)and(B), overall survival rate;(C) progression-free survival rate.

Fig 6. The integrated GSEA analysis.

Abbreviations: GSEA, gene set enrichment analysis; NES, normalized ES; NOM p-value, normalized p-value; FDR, false discovery rate.

Fig 7. Analysis of Gene Co-expression of PBX3 mRNA.

The circle diagram of the genes with positive and negative correlation with PBX3 mRNA expression (green: negative correlation, red: positive correlation).