Hua Yang, Ma Xiukun, Liu Xianglong, Yuan Xiangfei, Qin Hai, Zhang Xipeng
Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China.
Department of Surgery, Sino-Singapore Eco-City Hospital of Tianjin Medical University, Tianjin, China.
APMIS. 2017 Feb;125(2):93-100. doi: 10.1111/apm.12633. Epub 2016 Dec 28.
Rectal cancer is a common malignant tumor of the digestive tract, with a high incidence and high mortality. This study aimed to identify the potential biomarkers and therapeutic targets for rectal adenocarcinoma (RAC) metastasis. The expression profiling of RAC patients with metastasis and RAC patients without metastasis was downloaded from The Cancer Genome Atlas (TCGA) database. The datasets were used to identify the genes associated with RAC metastasis. Fifty up-regulated genes and seventeen down-regulated genes were identified in the primary tumor loci of RAC metastasis compared with non-metastasis. Sixty-seven dysregulated gens were conducted to construct the protein-protein network, and CCND3 was the hub protein. The dysregulated genes were significantly enriched in pancreatic secretion, cell adhesion molecules pathways, response to vitamin D of biological process, and retinoid binding of molecular function. Quantitative real-time polymerase chain reaction results demonstrated that CCND3, AQP3, PEG10, and RAB27B had the up-regulated tendency in RAC metastasis; ADCY1 had the down-regulated tendency in RAC metastasis. CCND3, AQP3, PEG10, RAB27B, and ADCY1 might play essential roles in the metastasis process of RAC through pancreatic secretion and cell adhesion molecules pathways. The five genes could be potential diagnosis biomarkers or therapeutic targets for RAC metastasis.
直肠癌是消化道常见的恶性肿瘤,发病率和死亡率都很高。本研究旨在确定直肠腺癌(RAC)转移的潜在生物标志物和治疗靶点。从癌症基因组图谱(TCGA)数据库下载了有转移的RAC患者和无转移的RAC患者的表达谱。这些数据集用于鉴定与RAC转移相关的基因。与无转移的RAC相比,在RAC转移的原发肿瘤位点中鉴定出50个上调基因和17个下调基因。对67个失调基因构建蛋白质-蛋白质网络,发现细胞周期蛋白D3(CCND3)是枢纽蛋白。这些失调基因在胰腺分泌、细胞黏附分子途径、对维生素D的生物学过程反应以及分子功能的视黄醇结合方面显著富集。定量实时聚合酶链反应结果表明,CCND3、水通道蛋白3(AQP3)、印记基因10(PEG10)和RAB27B在RAC转移中有上调趋势;腺苷酸环化酶1(ADCY1)在RAC转移中有下调趋势。CCND3、AQP3、PEG10、RAB27B和ADCY1可能通过胰腺分泌和细胞黏附分子途径在RAC转移过程中发挥重要作用。这五个基因可能是RAC转移的潜在诊断生物标志物或治疗靶点。