State Key Laboratory of Trauma, Burns and Combined Injury; Medical Center of Hematology, The Second Affiliated Hospital of Army Medical University, Key Subject of Chongqing, No. 83 Xinqiao Street, Shapingba District, Chongqing, 400037, PR China.
Department of Educational Technology, College of Basic Medical Sciences, Army Medical University, Chongqing, 400038, China.
BMC Med Genet. 2020 Oct 22;21(Suppl 1):174. doi: 10.1186/s12881-020-01108-9.
Deep vein thrombosis (DVT) is associated with stroke. Here, we hypothesize that genes associated with DVT may also play roles in the development of stroke.
we firstly conducted large-scale literature based disease-gene relationship data analysis to explore the genes implicated with DVT and stroke. Further, a mega-analysis was conducted for each of these genes that were linked to DVT but not stroke, using 11 independent stroke RNA expression datasets (176 stroke cases and 102 healthy controls). Then, a multiple linear regression (MLR) model was employed to study possible influential factors on the gene expression levels in stroke. After that, a functional pathway analysis was performed to identify the potential biological linkage between stroke and the target genes suggested by mega-analysis.
Over 81.10% genes implicated with DVT also suggested an association with stroke. Among the 24 DVT-specific genes, one DVT-inhibiting gene, SP1, presented significantly increased expression in stroke (LFC = 1.34, p-value = 0.0045). Pathway analysis showed that SP1 may play a therapeutic role in post-stroke patients by promoting multiple of stroke-inhibitors. Moreover, geographical region was indicated as an influential factor on the expression levels of SP1 in stroke samples (p-value = 0.037).
Our results suggested that DVT inhibitor SP1 could be a novel therapeutic target gene for post-stroke treatment. Further study of the potential relations between SP1 and stroke was guaranteed.
深静脉血栓形成(DVT)与中风有关。在这里,我们假设与 DVT 相关的基因也可能在中风的发展中起作用。
我们首先进行了大规模的基于文献的疾病-基因关系数据分析,以探索与 DVT 和中风相关的基因。进一步,我们对与 DVT 相关但与中风无关的这些基因进行了 Mega 分析,使用了 11 个独立的中风 RNA 表达数据集(176 例中风病例和 102 例健康对照)。然后,我们使用多元线性回归(MLR)模型研究了中风基因表达水平的可能影响因素。之后,我们进行了功能途径分析,以确定 Mega 分析提示的中风与靶基因之间的潜在生物学联系。
超过 81.10%与 DVT 相关的基因也提示与中风有关。在 24 个 DVT 特异性基因中,一个 DVT 抑制基因 SP1 在中风中表达显著增加(LFC=1.34,p 值=0.0045)。途径分析表明,SP1 可能通过促进多种中风抑制剂在中风后患者中发挥治疗作用。此外,地理位置被表明是中风样本中 SP1 表达水平的一个影响因素(p 值=0.037)。
我们的结果表明,DVT 抑制剂 SP1 可能是中风后治疗的一个新的治疗靶基因。进一步研究 SP1 与中风之间的潜在关系是有保证的。