Checkpoint kinase1 (CHK1) is an important biomarker in breast cancer having a role in chemotherapy response.

Publisher: Nature Publishing Group on behalf of Cancer Research UK Country of Publication: England NLM ID: 0370635 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-1827 (Electronic) Linking ISSN: 00070920 NLM ISO Abbreviation: Br J Cancer Subsets: MEDLINE

Publication: 2002- : London : Nature Publishing Group on behalf of Cancer Research UK
Original Publication: London, Lewis.

Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*drug therapy ; Breast Neoplasms/*pathology ; Protein Kinases/*metabolism ; alpha Karyopherins/*metabolism; Adolescent ; Adult ; Aged ; Breast Neoplasms/metabolism ; Cell Nucleus/metabolism ; Checkpoint Kinase 1 ; Cytoplasm/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Phosphorylation ; Signal Transduction ; Survival Analysis ; Treatment Outcome ; Young Adult

Background: Checkpoint kinase1 (CHK1), which is a key component of DNA-damage-activated checkpoint signalling response, may have a role in breast cancer (BC) pathogenesis and influence response to chemotherapy. This study investigated the clinicopathological significance of phosphorylated CHK1 (pCHK1) protein in BC.
Method: pCHK1 protein expression was assessed using immunohistochemistry in a large, well-characterized annotated series of early-stage primary operable invasive BC prepared as tissue microarray (n=1200).
Result: pCHK1 showed nuclear and/or cytoplasmic expression. Tumours with nuclear expression showed positive associations with favourable prognostic features such as lower grade, lower mitotic activity, expression of hormone receptor and lack of expression of KI67 and PI3K (P<0.001). On the other hand, cytoplasmic expression was associated with features of poor prognosis such as higher grade, triple-negative phenotype and expression of KI67, p53, AKT and PI3K. pCHK1 expression showed an association with DNA damage response (ATM, RAD51, BRCA1, KU70/KU80, DNA-PKCα and BARD1) and sumoylation (UBC9 and PIASγ) biomarkers. Subcellular localisation of pCHK1 was associated with the expression of the nuclear transport protein KPNA2. Positive nuclear expression predicted better survival outcome in patients who did not receive chemotherapy in the whole series and in ER-positive tumours. In ER-negative and triple-negative subgroups, nuclear pCHK1 predicted shorter survival in patients who received cyclophosphamide, methotrexate and 5-florouracil chemotherapy.
Conclusions: Our data suggest that pCHK1 may have prognostic and predictive significance in BC. Subcellular localisation of pCHK1 protein is related to its function.

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0 (Biomarkers, Tumor)
0 (KPNA2 protein, human)
0 (alpha Karyopherins)
EC 2.7.- (Protein Kinases)
EC 2.7.11.1 (CHEK1 protein, human)
EC 2.7.11.1 (Checkpoint Kinase 1)

Date Created: 20150218 Date Completed: 20150430 Latest Revision: 20181113

20250114

PMC4453942

10.1038/bjc.2014.576

25688741