Dysregulation of LINC00324 promotes poor prognosis in patients with glioma

Abstract

Background: LINC00324 is a long-stranded non-coding RNA, which is aberrantly expressed in various cancers and is associated with poor prognosis and clinical features. It involves multiple oncogenic molecular pathways affecting cell proliferation, migration, invasion, and apoptosis. However, the expression, function, and mechanism of LINC00324 in glioma have not been reported.

Material and methods: We assessed the expression of LINC00324 of LINC00324 in glioma patients based on data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) to identify pathways involved in LINC00324-related glioma pathogenesis.

Results: Based on our findings, we observed differential expression of LINC00324 between tumor and normal tissues in glioma patients. Our analysis of overall survival (OS) and disease-specific survival (DSS) indicated that glioma patients with high LINC00324 expression had a poorer prognosis compared to those with low LINC00324 expression. By integrating clinical data and genetic signatures from TCGA patients, we developed a nomogram to predict OS and DSS in glioma patients. Gene set enrichment analysis (GSEA) revealed that several pathways, including JAK/STAT3 signaling, epithelial-mesenchymal transition, STAT5 signaling, NF-κB activation, and apoptosis, were differentially enriched in glioma samples with high LINC00324 expression. Furthermore, we observed significant correlations between LINC00324 expression, immune infiltration levels, and expression of immune checkpoint-related genes (HAVCR2: r = 0.627, P = 1.54e-77; CD40: r = 0.604, P = 1.36e-70; ITGB2: r = 0.612, P = 6.33e-7; CX3CL1: r = -0.307, P = 9.24e-17). These findings highlight the potential significance of LINC00324 in glioma progression and suggest avenues for further research and potential therapeutic targets.

Conclusion: Indeed, our results confirm that the LINC00324 signature holds promise as a prognostic predictor in glioma patients. This finding opens up new possibilities for understanding the disease and may offer valuable insights for the development of targeted therapies.

Fig 1. Expression of LINC00324 in glioma.

(A) The expression of LINC00324 in glioma and normal tissues(*, P<0.05). (B) Order of receiver operating characteristic curves for LINC00324 expression in normal and glioma tissues. TPR, true positive rate; FPR, false positive rate.

Fig 2. Clinical relevance of LINC00324 in glioma patients.

For OS outcome, (A) Kaplan-Meier plot of the LINC00324 signature and overall survival, (B) ROCs for 1-, 3- and 5-year survival prediction, and (C) AUCs for predicting 1–10 year survival. For DSS outcome, (D) Kaplan-Meier plot of the LINC00324 signature and disease-specific survival. (E) ROCs for 1-, 3- and 5-year disease-specific survival prediction, (F) AUCs for predicting 1–10 years disease-specific survival. OS, overall survival; DSS, disease-specific survival; ROC, receiver operating characteristic curve; AUC, area under ROC curve; TPR, true positive rate; FPR, false positive rate.

Fig 3. Nomogram development and validation.

For OS(A) and DSS(D), hazard ratios and P-value of the constituents involved in multivariate Cox regression considering clinical information and prognostic LINC00324 in glioma. Nomogram to predict the 1-, 3- and 5-year OS(B) and DSS(E) rate of glioma patients. Calibration curve for the OS(C) and DSS(F) nomogram model in glioma. A dashed diagonal line represents the ideal nomogram. OS, overall survival; DSS, disease-specific survival; G2, grade 2; G3, grade 3; G4, grade 4; CR, complete remission; PD, progressive disease; PR, partial remission; SD, stable disease.

Fig 4

Expression of LINC00324 in a different age stage(A), pathologic stage(B), histological type(C), IDH1 status(D), 1p/19q codeletion status(E), and primary therapy outcome(F) of glioma patients, respectively. G2, grade 2; G3, grade 3; G4, grade 4; CR, complete remission; PD, progressive disease; PR, partial remission; SD, stable disease(*, P<0.05;**, P<0.01;***, P<0.001).

Fig 5. Differential expression analysis of high- and low-expression LINC00324 groups in the volcano map.

Fig 6. Enrichment plots from gene set enrichment analysis (GSEA).

Fig 7

Enrichment plots from GO (A, B and C) and KEGG (D) analysis. GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; BP, biological process; CC, cellular component; MF, molecular function.

Fig 8. Visual map of the protein-protein interaction network for high- and low-expression LINC00324 groups.

Fig 9. Correlation between LINC00324 expression and immune infiltration.

Fig 10

Association between LINC00324 and HAVCR2(A), CD40(B), ITGB2(C), CX3CL1(D), IFNA2(E) and ADORA2A(F) expression in glioma patients, respectively.