Department of General and Visceral Surgery, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
Ulm University, Institute of General Physiology, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
BMC Cancer. 2018 Feb 6;18(1):140. doi: 10.1186/s12885-018-4019-0.
Colorectal cancer (CRC) is the fourth leading cause of cancer related deaths worldwide and prognosis in advanced tumor stage still remains poor. Since CK1 isoforms have been reported to be deregulated in several tumor entities CK1 has emerged as a novel drug target in cancer therapy. In this study we set out to investigate whether CK1α might have the potential to serve as prognostic marker.
CK1α RNA and protein expression levels in healthy and tumor tissue of CRC patients were analyzed using quantitative real-time PCR and Western Blot analysis, respectively. Prognostic relevance was investigated by correlating obtained CK1α expression levels with patients' survival rate generating Kaplan-Meier survival plots.
It could be shown that CK1α is overexpressed in colorectal tumor tissue compared to normal tissue and CK1α overexpression in tumor tissue correlates with poor survival in CRC patients. Results become more significant when only considering patients with high-grade tumors, as well as patients assigned to UICC II and UICC III stage. Furthermore, Cox regression analysis revealed that CK1α is an independent prognostic factor. In addition, tumors expressing decreased levels of the kinase reveal positive effects on overall survival when localized in the right colon compared to those in the left side.
In summary, this study provides evidence for the first time that CK1α RNA levels might serve as prognostic marker for CRC.
结直肠癌（CRC）是全球癌症相关死亡的第四大主要原因，晚期肿瘤的预后仍然较差。由于 CK1 同工型已在几种肿瘤实体中被报道失调，因此 CK1 已成为癌症治疗的新药物靶点。在这项研究中，我们着手研究 CK1α 是否有可能作为预后标志物。
使用定量实时 PCR 和 Western Blot 分析分别分析了 CRC 患者的健康组织和肿瘤组织中的 CK1α RNA 和蛋白表达水平。通过生成 Kaplan-Meier 生存图，将获得的 CK1α 表达水平与患者的生存率相关联，来研究预后相关性。
结果表明，与正常组织相比，结直肠肿瘤组织中 CK1α 过表达，并且肿瘤组织中 CK1α 的过表达与 CRC 患者的不良预后相关。仅考虑高级别肿瘤患者以及 UICC II 和 UICC III 期患者时，结果更为显著。此外，Cox 回归分析表明 CK1α 是独立的预后因素。此外，与左侧相比，当位于右侧结肠时，表达降低的激酶的肿瘤对总生存期有积极影响。
综上所述，本研究首次提供了证据，表明 CK1α RNA 水平可能作为 CRC 的预后标志物。
