Analysis of the EGFR Amplification and CDKN2A Deletion Regulated Transcriptomic Signatures Reveals the Prognostic Significance of SPATS2L in Patients With Glioma

Abstract

Purpose: This study was conducted in order to analyze the prognostic effects of epidermal growth factor receptor (EGFR) and CDKN2A alterations and determine the prognostic significance of EGFR and CDKN2A alterations on regulated genes in patients with glioblastoma (GBM) or lower grade glioma (LGG).Methods: The alteration frequencies of EGFR and CDKN2A across 32 tumor types were derived from cBioPortal based on The Cancer Genome Atlas (TCGA) datasets. The Kaplan–Meier analysis was used to determine the prognostic significance of EGFR and CDKN2A alterations. EGFR and CDKN2A alterations on regulated expression signatures were identified from RNA-seq data in the TCGA GBM datasets. The prognostic significance of EGFR and CDKN2A alterations on regulated genes in patients with glioma was determined using the TCGA and the Chinese Glioma Genome Atlas (CGGA) datasets.Results: Compared with the other 31 tumor types, EGFR amplification and CDKN2A deletion particularly occurred in patients with GBM. GBM patients with EGFR amplification or CDKN2A deletion demonstrated poor prognosis. Statistical analysis showed the coexistence of EGFR alteration and CDKN2A deletion in GBM patients. We identified 864 genes which were commonly regulated by EGFR amplification and CDKN2A deletion, and those genes were highly expressed in brain tissues and associated with the cell cycle, EBRR2, and MAPK signaling pathways. Spermatogenesis-associated serine-rich 2-like gene (SPATS2L) was upregulated in GBM patients with EGFR amplification or CDKN2A alteration. Higher expression levels of SPATS2L were associated with worse prognosis in patients with GBM in both TCGA and CGGA datasets. Moreover, the expression levels of SPATS2L were higher in patients with a mesenchymal subtype of GBM. Statistical analysis also showed that the coexistence of EGFR alteration and CDKN2A deletion was significant in patients with LGG. SPATS2L was upregulated in LGG patients with EGFR amplification or CDKN2A alteration. Furthermore, higher expression levels of SPATS2L were associated with worse prognosis in patients with LGG in both TCGA and CGGA datasets. The expression levels of SPATS2L were higher in patients with an astrocytoma subtype of LGG. Finally, the coexistence and unfavorable prognostic effects of EGFR amplification and CDKN2A alteration were validated using the Memorial Sloan Kettering Cancer Center (MSKCC) glioma datasets.Conclusions: EGFR amplification and CDKN2A deletion of the regulated gene SPATS2L have significant prognostic effects in patients with GBM or LGG.

RETRACTED ARTICLE: Long non-coding RNA HOXA11 antisense RNA upregulates spermatogenesis-associated serine-rich 2-like to enhance cisplatin resistance in laryngeal squamous cell carcinoma by suppressing microRNA-518a

“…Through a series of experiments, spermatogenesis-associated serine-rich 2-like (SPATS2L) was confirmed as a downstream gene of miR-518a. SPATS2L is ubiquitously expressed in multiple tissues and its overexpression is related to the carcinogenesis of glioma and hepatocellular carcinoma [ 33 , 34 ]. Our results demonstrated that SPATS2L was upregulated in CDDP-resistant LSCC, and miR-518a inhibited SPATS2L expression by direct interaction.…”

Sedoheptulose Kinase SHPK Expression in Glioblastoma: Emerging Role of the Nonoxidative Pentose Phosphate Pathway in Tumor Proliferation

“…For example, the most significant genes in each group were IDH1, which associates its mutated state with lower SHPK expression, and EGFR, which instead associates its mutated state with higher SHPK expression. This agrees perfectly with what we found in the literature, where strong evidence shows that IDH1 mutation is associated with a better prognosis for GBM patients [ 54 , 55 , 56 ], and on the other hand, EGFR mutation with a worse one [ 57 ].…”

CCT6A and CHCHD2 Are Coamplified with EGFR and Associated with the Unfavorable Clinical Outcomes of Lung Adenocarcinoma

“…EGFR amplification was associated with the LUAD overall survival [ 51 ]. Similarly, LUAD with CCT6A amplification had poor progression-free survival contrast with LUAD without CCT6A amplification ( Figure 1(c) ).…”