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细胞周期蛋白依赖性激酶1δ(CK1δ)表达降低预示着结直肠癌患者生存期延长。

Decreased CK1δ expression predicts prolonged survival in colorectal cancer patients.

作者信息

Richter Julia, Rudeck Steven, Kretz Anna-Laura, Kramer Klaus, Just Steffen, Henne-Bruns Doris, Hillenbrand Andreas, Leithäuser Frank, Lemke Johannes, Knippschild Uwe

机构信息

Department of General and Visceral Surgery, Surgery Centre, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany.

Department of Internal Medicine II, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany.

出版信息

Tumour Biol. 2016 Jul;37(7):8731-9. doi: 10.1007/s13277-015-4745-8. Epub 2016 Jan 7.

Abstract

Cancers arising from the large intestine or rectum are called colorectal cancer (CRC) and represent the fourth leading cause of cancer-related death worldwide. Since casein kinase 1 (CK1) isoforms are involved in many cellular processes and have been reported to be deregulated in various tumor entities, CK1 has become an interesting drug target. In this study, we examined the potential of CK1δ expression levels in tumor tissue of CRC patients as a prognostic biomarker. We show by quantitative RNA expression analyses that decreased CK1δ expression levels in tumor tissue predict prolonged survival rates. Random sampling of CK1δ stained tumor tissue indicates that CK1δ gene expression corresponds with CK1δ protein expression. Especially in low grade (grade 1, grade 2) and in UICC II/III classified tumors decreased CK1δ RNA levels correlate with significantly improved survival rates when the tumor was located in the right colon. We furthermore found gender-specific differences within these subgroups, revealing most significant increase in overall survival rates in male patients with tumors in right colon expressing low levels of CK1δ RNA. Results become even clearer, when only male patients over 50 years were considered. Together, these findings support the assumption that CK1δ might be a prognostic biomarker for CRC thereby providing an interesting drug target for the development of new therapy concepts.

摘要

起源于大肠或直肠的癌症称为结直肠癌(CRC),是全球癌症相关死亡的第四大主要原因。由于酪蛋白激酶1(CK1)亚型参与许多细胞过程,并且据报道在各种肿瘤实体中失调,CK1已成为一个有趣的药物靶点。在本研究中,我们检测了CRC患者肿瘤组织中CK1δ表达水平作为预后生物标志物的潜力。我们通过定量RNA表达分析表明,肿瘤组织中CK1δ表达水平降低预示着生存率延长。对CK1δ染色的肿瘤组织进行随机抽样表明,CK1δ基因表达与CK1δ蛋白表达相对应。特别是在低级别(1级、2级)以及UICC II/III分类的肿瘤中,当肿瘤位于右半结肠时,CK1δ RNA水平降低与生存率显著提高相关。我们还在这些亚组中发现了性别差异,揭示了右半结肠表达低水平CK1δ RNA的男性患者总体生存率有最显著的提高。当仅考虑50岁以上的男性患者时,结果更加明显。总之,这些发现支持了CK1δ可能是CRC预后生物标志物的假设,从而为新治疗方案的开发提供了一个有趣的药物靶点。

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