Al-Khatib Sohaib M, Al-Bzour Ayah N, Al-Majali Mohammad N, Sa'd Laila M, Alramadneh Joud A, Othman Nour R, Al-Mistarehi Abdel-Hameed, Alomari Safwan
Department of Pathology and Laboratory Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan.
Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan.
Cancers (Basel). 2024 Mar 10;16(6):1112. doi: 10.3390/cancers16061112.
Serpins are serine proteinase inhibitors, with several serpins being overexpressed in cancer cells. Thus, we aim to analyze the single-nucleotide polymorphism (SNP) of and its association with GBM survival. A cohort of 63 GBM patients recruited from King Abdullah University Hospital in Jordan underwent polymorphism analysis and overall survival (OS) assessments. The Cancer Genome Atlas (GBM) cohort was useful for validation. We constructed a risk score using the principal component analysis for the following Serpin genes: and , and patients were grouped into high- vs. low-risk groups based on the median cutoff. Univariable Cox models were used to study the survival outcomes. We identified a significant association between rs4940595 and survival. In the TCGA cohort, alterations showed worse OS. Univariable Cox showed worse PFS outcomes with higher SERPINB5 and SERPINB6 expression. A Serpin B 5-gene risk score showed a trend towards worse PFS in the high-risk group. Upregulated DEGs showed GO enrichment in cytokine regulation and production, positive regulation of leukocyte activation, and the MAPK cascade. The high-risk group showed a significantly higher infiltration of M2 macrophages and activated mast cells. Our findings showed a significant role of the Serpin B family in GBM survival in the Jordanian population.
丝氨酸蛋白酶抑制剂（Serpins）是丝氨酸蛋白酶的抑制剂，有几种丝氨酸蛋白酶抑制剂在癌细胞中过表达。因此，我们旨在分析[具体基因名称未给出]的单核苷酸多态性（SNP）及其与胶质母细胞瘤（GBM）生存的关联。从约旦阿卜杜拉国王大学医院招募的63例GBM患者队列进行了多态性分析和总生存（OS）评估。癌症基因组图谱（GBM）队列用于验证。我们使用主成分分析对以下丝氨酸蛋白酶抑制剂基因构建风险评分：[具体基因名称未给出]，并根据中位数临界值将患者分为高风险组和低风险组。使用单变量Cox模型研究生存结果。我们发现rs4940595与生存之间存在显著关联。在TCGA队列中，[具体基因名称未给出]改变显示出更差的总生存期。单变量Cox分析显示，较高的丝氨酸蛋白酶抑制剂B5（SERPINB5）和丝氨酸蛋白酶抑制剂B6（SERPINB6）表达导致更差的无进展生存期（PFS）结果。丝氨酸蛋白酶抑制剂B5基因风险评分显示高风险组的无进展生存期有变差趋势。上调的差异表达基因（DEGs）在细胞因子调节和产生、白细胞活化的正调节以及丝裂原活化蛋白激酶（MAPK）级联反应中显示出基因本体（GO）富集。高风险组显示M2巨噬细胞和活化肥大细胞的浸润显著更高。我们的研究结果表明丝氨酸蛋白酶抑制剂B家族在约旦人群的GBM生存中发挥了重要作用。
