Differential Expression of PEG10 Contributes to Aggressive Disease in Early Versus Late-Onset Colorectal Cancer.
Differential Expression of PEG10 Contributes to Aggressive Disease in Early Versus Late-Onset Colorectal Cancer.
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DOI：
10.1097/dcr.0000000000001774
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发表时间：
2020-12
影响因子：
3.9
通讯作者：
Tsikitis VL
中科院分区：
文献类型：
--
作者：
Watson KM;Gardner IH;Byrne RM;Ruhl RR;Lanciault CP;Dewey EN;Anand S;Tsikitis VL
结直肠癌是癌症相关死亡的主要原因。早发性结直肠癌（年龄≤45岁）正在增加，并与晚期疾病相关。虽然结直肠癌的不同分子亚型已被表征，但尚不清楚是否存在年龄相关的分子差异。我们试图确定早发和晚发（年龄≥65岁）结直肠癌之间基因表达的差异。我们回顾了我们机构的结直肠癌登记处，并确定了结直肠癌患者的组织标本可用于分析。我们使用癌症基因组图谱来初步确定早发型和晚发型结直肠癌之间基因表达的差异。体外实验在两种结直肠癌细胞系上进行。这项研究是在一家三级医疗中心进行的。纳入了诊断时早发（N=28）或晚发（年龄≥65岁，N=38）的患者。主要结果是早发和晚发结直肠癌患者的差异基因表达。次要结局为患者死亡率。使用癌症基因组图谱，七个基因在年轻患者中的表达增加。只有PEG 10被定量聚合酶链反应充分表达，并且在我们的早发组中表达增加。多变量线性回归分析表明，年龄是PEG 10表达增加的重要独立预测因子。来自癌症基因组图谱的结果数据表明，PEG 10与总体生存率低相关。在HCT-116和HT-29细胞系中的体外研究表明，PEG 10有助于结直肠癌的细胞增殖和侵袭。组织样本来自福尔马林固定的石蜡包埋切片。许多患者没有突变状态可供审查。PEG 10在早发性结直肠癌中差异表达，可能在功能上有助于肿瘤细胞增殖和侵袭。PEG 10表达增加与总生存期降低相关。参见http://links.lww.com/DCR/Bxxx上的视频摘要。
Colorectal cancer is a leading cause of cancer-related death. Early onset colorectal cancer (age ≤45 years) is increasing and associated with advanced disease. While distinct molecular subtypes of colorectal cancer have been characterized, it is unclear whether age-related molecular differences exist. We sought to identify differences in gene expression between early and late onset (age ≥65 years) colorectal cancer. We performed a review of our institution’s colorectal cancer registry and identified patients with colorectal cancer with tissue specimens available for analysis. We used The Cancer Genome Atlas to initially identify differences in gene expression between early and late onset colorectal cancer. In vitro experiments were performed on two colorectal cancer cell lines. The study was conducted at a tertiary medical center. Patients with early onset (N=28) or late onset (age ≥65 years old, N=38) at time of diagnosis were included. The primary outcome was differential gene expression in patients with early versus late onset colorectal cancer. The secondary outcome was patient mortality. Seven genes had increased expression in younger patients using The Cancer Genome Atlas. Only PEG10 was sufficiently expressed with quantitative polymerase chain reaction and had increased expression in our early onset group. Multivariable linear regression analysis identified age as a significant independent predictor of increased PEG10 expression. Outcomes data from The Cancer Genome Atlas suggests that PEG10 is associated with poor overall survival. In vitro studies in HCT-116 and HT-29 cell lines showed PEG10 contributes to cellular proliferation and invasion in colorectal cancer. Tissue samples were from formalin-fixed paraffin-embedded slides. Many patients did not have mutational status for review. PEG10 is differentially expressed in early onset colorectal cancer and may functionally contribute to tumor cell proliferation and invasion. Increase in PEG10 expression correlates with decreased overall survival. See Video Abstract at http://links.lww.com/DCR/Bxxx.