In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 699-699
Kurzfassung:
DNA polymerase eta (Pol β, POLH) is a eukaryotic DNA polymerase involved in DNA repair by translesion synthesis. To address whether Pol ≤ impacts breast cancer survival, we conducted a retrospective outcome study on 145assessable cases of breast cancers collected from affiliated hospital of Zhejiang University (ZJU set). The results were validated on six published microarray data sets (1,154 cases) with pathoclinical and follow-up information. In the ZJU set, the protein levels of Pol ≤ were determined by IHC. The specificity of antibody against Pol ≤ was validated by using peptide blocking assay. It was shown that protein expression level of Pol ≤ positively correlates with cell proliferative marker Ki-67 (trends P=0.019). The Kaplan-Meier analysis revealed that Pol ≤ was significantly related that better overall survival in breast cancer patients who received chemotherapy or radiotherapy (Log rank p=0.003). Multivariate COX analysis further confirmed that the hazard ratio (HR) of Pol ≤ for overall and progress-free survival were 0.23(95% CI 0.05-0.95) and 0.32(0.11-0.96). Further stratification analysis demonstrated that Pol ≤ prognoses better survival in Luminal A and B molecular subtypes (HR=0.155 95% CI 0.04-0.62), but not HER 2 Positive or Triple negative breast cancer. Above findings were further validated in public microarray database. In Ivshina's dataset, the increase of POLH mRNA was significantly and negatively related with lymphnode involvement in a dose-dependent manner (trend p=0.044). The Kaplan-Meier analysis also revealed that the mRNA levels of POLH was significantly related to progress-free survival of breast cancer. In Chin's data, multivariate COX analysis also revealed that the HR increased significantly as with increase of POLH mRNA levels (HR= 0.22 95% CI 0.03-0.86, highest quartile vs. lowest quartile). Above findings suggested that the protein and mRNA expression levels of Pol ≤ prognoses better survival in breast cancer, especially in Luminal A or B breast cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 699. doi:1538-7445.AM2012-699
Materialart:
Online-Ressource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-699
Sprache:
Englisch
Verlag:
American Association for Cancer Research (AACR)
Publikationsdatum:
2012
ZDB Id:
2036785-5
ZDB Id:
1432-1
ZDB Id:
410466-3
