Decreased CK1δ expression predicts prolonged survival in colorectal cancer patients
Decreased CK1δ expression predicts prolonged survival in colorectal cancer patients
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DOI：
10.1007/s13277-015-4745-8
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发表时间：
2016-07-01
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影响因子：
--
通讯作者：
Knippschild, Uwe
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文献类型：
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作者：
Richter, Julia;Rudeck, Steven;Knippschild, Uwe
大肠或直肠癌称为结直肠癌（CRC），是全球癌症相关死亡的第四大原因。由于酪蛋白激酶1（CK 1）亚型参与许多细胞过程，并已被报道在各种肿瘤实体中失调，CK 1已成为一个有趣的药物靶点。在这项研究中，我们研究了CRC患者肿瘤组织中CK 1 δ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CK 1 δ表达水平降低可预测生存率延长。CK 1 δ染色的肿瘤组织的随机取样表明CK 1 δ基因表达与CK 1 δ蛋白表达相对应。特别是在低级别（1级，2级）和UICC II/III分类的肿瘤中，当肿瘤位于右结肠时，CK 1 δ RNA水平降低与生存率显著提高相关。我们还发现了这些亚组中的性别特异性差异，揭示了在表达低水平CK 1 δ RNA的右半结肠肿瘤的男性患者中，总生存率的增加最显著。当只考虑50岁以上的男性患者时，结果变得更加清晰。总之，这些发现支持了CK 1 δ可能是CRC的预后生物标志物的假设，从而为开发新的治疗概念提供了一个有趣的药物靶点。
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 CK1 delta expression levels in tumor tissue of CRC patients as a prognostic biomarker. We show by quantitative RNA expression analyses that decreased CK1 delta expression levels in tumor tissue predict prolonged survival rates. Random sampling of CK1 delta stained tumor tissue indicates that CK1 delta gene expression corresponds with CK1 delta protein expression. Especially in low grade (grade 1, grade 2) and in UICC II/III classified tumors decreased CK1 delta 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 CK1 delta RNA. Results become even clearer, when only male patients over 50 years were considered. Together, these findings support the assumption that CK1 delta might be a prognostic biomarker for CRC thereby providing an interesting drug target for the development of new therapy concepts.