PMC9366390_01
Case presentation. (A) Timeline of disease diagnosis and treatment. (B-D) Magnetic resonance imaging (MRI) obtained during three resections. The red arrows indicate the tumor locations. (E) Slides of resected tissue collected from the same patient at three timepoints in the disease course were subjected to HE staining (100X).
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As shown in Figure 1A, he underwent the initial tumor resection of the right frontal lobe. Magnetic resonance imaging (MRI) revealed a heterogeneous tumor mass measuring 4 x 4 x 4 cm in the right lobe (Figure 1B). The MRI scan further confirmed that the tumor recurred and was significantly larger (Figure 1C). Two years prior to the current presentation, in 2020, the MRI scan showed an enhancing lesion in the right frontal lobe that was significantly increased in size, suggesting a worsening high-grade glioma (Figure 1D). The pathologic exam showed that the tumor underwent malignant transformation from an early disease stage (1st and 2nd resected tumors) to a late disease stage (3rd resected tumor) (Figure 1E) and was positive for GFAP, Ki-67, S-100, Syn and Olig-2 expression and negative for CD99, EMA, CgA, AE1/AE3 and LCA expression.
ISL2 was highly expressed with recurrence of oligodendroglioma. (A) Histopathological examination. The expression of Ki-67, ISL2, VEGFA, VMT and CD31/PAS in specimens collected from the same patient at three timepoints in the disease course was evaluated by IHC staining (40X). (B) The mRNA expression of Ki-67, ISL2, VEGFA, VMT and CD31 in specimens collected from the same patient at three timepoints in the disease course was determined by RT-PCR. **p<0.002; ##p<0.002.
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CD31 in the specimens, as determined by RT-PCR (Figure 2B). Collectively, these results showed that ISL2 and angiogenesis were associated with the malignant transformation of oligodendroglioma in this patient.
ISL2 correlates with poor overall survival in LGG patients. (A, B) The prognostic significance of ISL2 in LGG (A) and GBM (B) glioma tissues was analyzed in the TCGA database. (n (LGG)=509; n (GBM)=153). (C, D) The overall survival of female and male LGG patients with different ISL2 expression levels (n (female)=227; n (male)=282). (E, F) Kaplan-Meier survival curve showing the effects of isocitrate hydrogenase 1 (IDH1) status on overall survival in LGG patients with high versus low ISL2 expression levels. WT, wild-type; MT, mutated. HR (High exp) represents the risk coefficient of the samples in the high expression group relative to the samples in the low expression group: if HR > 1 means the gene is a risk factor, if HR < 1 means the gene is a protective factor. 95% CL represents the HR confidence interval; median time represents the time (in years) corresponding to a survival rate of 50% in both the high and low expression groups.
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In LGG, the OS of patients with high ISL2 expression (ISL2High) was significantly worse than that of patients with low ISL2 expression (ISL2Low) (Figure 3A). In contrast, there was no difference in prognosis between the ISL2High and ISL2Low patient groups in GBM (Figure 3B). Kaplan-Meier survival analysis revealed that the median survival times of female and male LGG patients were similar (Figures 3C, D). Kaplan-Meier analysis showed that IDH1 mutation status did not affect the negative correlation between ISL2 expression and OS ( Figures 3E, F ).