Department of Pathology, Faculty of Medicine, King Abdulaziz University, Rabigh, Kingdom of Saudi Arabia.
Neuromuscular Unit, King Fahad Medical Research Center, Jeddah, Saudi Arabia.
J Neurooncol. 2023 Jul;163(3):693-705. doi: 10.1007/s11060-023-04385-5. Epub 2023 Jul 4.
Corticosteroid is commonly used before surgery to control cerebral oedema in brain tumours and is frequently continued throughout treatment. Its long-term effect of on the recurrence of WHO-Grade 4 astrocytoma remains controversial. The interaction between corticosteroid, SRC-1 gene and cytotoxic T-cells has never been investigated.
A retrospective cohort of 36 patients with WHO-Grade 4 astrocytoma were examined for CD8 + T-cell and SRC-1 gene expressions through IHC and qRT-PCR. The impact of corticosteroid on CD8T-cells infiltration, SRC-1 expression, and tumour recurrence was analyzed.
The mean patients age was 47-years, with a male to female ratio 1.2. About 78% [n = 28] of the cases showed reduced or no CD8T-cell expression while 22% [n = 8] of cases have showed medium to high CD8T-cell expression. SRC-1 gene was upregulated in 5 cases [14%] and 31 cases [86%] showed SRC-1 downregulation. The average of total days and doses of administered corticosteroid from the preoperative period to the postoperative period was at range of 14-106 days and 41-5028 mg, respectively. There was no significant statistical difference in RFI among tumours expressing high or low CD8T-cells when corticosteroid was administered in recommended or exceeded doses [p-value = 0.640]. There was a significant statistical difference in RFI between CD8T-Cell expression and SRC-1 gene dysregulation [p-value = 002]. Tumours with high CD8T T-cell expression and SRC-1 gene downregulation had late recurrence.
Corticosteroid treatment can directly affect the SRC-1 gene regulation but does not directly influence cytotoxic T-cells infiltration or tumor progression. However, SRC-1 gene downregulation can facilitate late tumor recurrence.
皮质类固醇在脑肿瘤手术前常用于控制脑水肿,并且在治疗过程中经常持续使用。其对世界卫生组织(WHO)四级星形细胞瘤复发的长期影响仍存在争议。皮质类固醇、SRC-1 基因和细胞毒性 T 细胞之间的相互作用从未被研究过。
通过免疫组化和 qRT-PCR 检查了 36 名 WHO 四级星形细胞瘤患者的 CD8+T 细胞和 SRC-1 基因表达情况。分析了皮质类固醇对 CD8+T 细胞浸润、SRC-1 表达和肿瘤复发的影响。
患者平均年龄为 47 岁,男女比例为 1.2。约 78%(n=28)的病例显示 CD8+T 细胞表达减少或缺失,而 22%(n=8)的病例显示中至高 CD8+T 细胞表达。SRC-1 基因在 5 例(14%)中上调,31 例(86%)下调。从术前到术后皮质类固醇给药的总天数和剂量范围分别为 14-106 天和 41-5028mg。当皮质类固醇以推荐剂量或超过剂量给药时,高或低 CD8+T 细胞表达的肿瘤之间的 RFI 无显著统计学差异(p 值=0.640)。CD8+T 细胞表达与 SRC-1 基因失调之间存在显著统计学差异(p 值=0.002)。高 CD8+T 细胞表达和 SRC-1 基因下调的肿瘤复发较晚。
皮质类固醇治疗可直接影响 SRC-1 基因的调控,但不会直接影响细胞毒性 T 细胞的浸润或肿瘤进展。然而,SRC-1 基因下调可促进肿瘤的晚期复发。