a Department of Pancreatic Cancer , National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital , Tianjin , China.
b Department of Gastrointestinal Cancer Biology , Tianjin Medical University Cancer Institute and Hospital , Tianjin , China.
Cancer Biol Ther. 2019;20(6):787-798. doi: 10.1080/15384047.2018.1564565. Epub 2019 Feb 3.
Pancreatic cancer is one of the most malignant diseases and has a poor prognosis. The screening and validation of biomarkers with predictive value for prognosis and treatment efficacy are important. To identify potential prognostic markers of pancreatic cancer patients, we conducted a study that included 99 pancreatic cancer patients. Three patients with PFS>18 months were enrolled in the treat group, and three patients with PFS<12 months were enrolled in the control group. Differentially expressed genes (DEGs) between these two groups were analyzed by whole-genome expression microarray. A total of 178 DEGs were identified, including 110 up-regulated and 68 down-regulated genes. Next, 24 candidate genes were selected for validation by qPCR based on fold change and previous studies. The results showed that the mRNA levels of four candidate genes, including ACSL5, SLC44A4, LOX, and TOX3, were correlated with PFS. Immunohistochemical staining was performed to validate the protein expression levels of these four markers. The results showed that patients with LOX , ACSL5 and TOX3 expression had a significantly shorter PFS than those with LOX , ACSL5 and TOX3 expression. Multivariable analysis revealed differentiation, tumor stage, LOX expression, and ACSL5 expression were independent prognostic factors for PFS. Then, we use the TCGA database to explore the underlying mechanism of LOX influence pancreatic cancer progression. Protein-protein interaction network of ACSL5 was established by STRING to uncover the potential regulation mechanism. Our findings reveal that LOX and ACSL5 are potential prognostic markers for the prognosis of pancreatic cancer patients.
胰腺癌是最恶性的疾病之一，预后不良。筛选和验证具有预测预后和治疗效果的生物标志物非常重要。为了鉴定胰腺癌患者的潜在预后标志物，我们进行了一项研究，纳入了 99 例胰腺癌患者。将 3 例无进展生存期（PFS）>18 个月的患者纳入治疗组，将 3 例 PFS<12 个月的患者纳入对照组。通过全基因组表达微阵列分析两组之间的差异表达基因（DEGs）。共鉴定出 178 个 DEGs，包括 110 个上调基因和 68 个下调基因。接下来，根据 fold change 和之前的研究，选择了 24 个候选基因通过 qPCR 进行验证。结果表明，4 个候选基因（ACSL5、SLC44A4、LOX 和 TOX3）的 mRNA 水平与 PFS 相关。进行免疫组织化学染色以验证这四个标志物的蛋白表达水平。结果表明，LOX、ACSL5 和 TOX3 表达的患者 PFS 明显短于 LOX、ACSL5 和 TOX3 表达的患者。多变量分析显示，分化、肿瘤分期、LOX 表达和 ACSL5 表达是 PFS 的独立预后因素。然后，我们使用 TCGA 数据库来探讨 LOX 影响胰腺癌进展的潜在机制。通过 STRING 建立 ACSL5 的蛋白质-蛋白质相互作用网络，以揭示潜在的调控机制。我们的研究结果表明，LOX 和 ACSL5 是预测胰腺癌患者预后的潜在标志物。
