title: Decreased CK1δ expression predicts prolonged survival in colorectal cancer patients.
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.
authors.affiliation: Department of General and Visceral Surgery, Surgery Centre, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Richter
authors.affiliation: Department of Internal Medicine II, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
authors.forename: Steven
authors.initials: S
authors.lastname: Rudeck
authors.affiliation: Department of General and Visceral Surgery, Surgery Centre, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
authors.forename: Anna-Laura
authors.initials: AL
authors.lastname: Kretz
authors.affiliation: Department of General and Visceral Surgery, Surgery Centre, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Kramer
authors.affiliation: Department of Internal Medicine II, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Just
authors.affiliation: Department of General and Visceral Surgery, Surgery Centre, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Henne-Bruns
authors.affiliation: Department of General and Visceral Surgery, Surgery Centre, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hillenbrand
authors.affiliation: Department of Pathology, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Leithäuser
authors.affiliation: Department of General and Visceral Surgery, Surgery Centre, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Lemke
authors.affiliation: Department of General and Visceral Surgery, Surgery Centre, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany. uwe.knippschild@uniklinik-ulm.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Knippschild
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D048148:Casein Kinase Idelta / Q000235:genetics*; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012313:RNA / Q000235:genetics; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D012313:RNA; D048148:Casein Kinase Idelta
keywords: CK1δ; Colorectal cancer; Outcome; Prognosis; Prognostic marker; Survival