Elevated expression of POLD1 is associated with poor prognosis in breast cancer

POLD1 表达升高与乳腺癌预后不良相关

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作者:Qinghong Qin, Qixing Tan, Jinyuan Li, Weiping Yang, Bin Lian, Qinguo Mo, Changyuan Wei

Abstract

Polymerase δ catalytic subunit gene 1 (POLD1) may serve an important function in the development of tumors. However, its role in breast cancer remains unclear. The aim of the present study was to observe the expression and the function of POLD1 in breast cancer. A total of 84 patients with invasive breast carcinoma were recruited between 2011 and 2013. The expression of POLD1 was detected in paired tumor and adjacent normal tissues. Gene expression level of POLD1 was assessed using reverse transcription quantitative polymerase chain reaction. The protein expression of POLD1 was assessed using western blot analysis. The association between the clinicopathological features of patients with breast cancer and POLD1 expression was analyzed using a χ2 test. Disease-free survival (DFS) was analyzed using Kaplan-Meier method, and Cox regression analysis was performed to investigate clinicopathological significance of POLD1 expression. Additionally, the effects of POLD1 in regulating cell cycle and proliferation of MCF-7 cells were evaluated in vitro. The results demonstrated that gene and protein expression levels of POLD1 were significantly elevated in breast cancer tissues compared with those in adjacent normal tissues. Increased expression of POLD1 was significantly associated with positive lymph node status (P=0.028), histological grade (P=0.025), p53 status (P<0.001) and ki-67 index (P=0.020). Survival analysis demonstrated that increased expression of POLD1 was associated with poor DFS (P=0.033). Additionally, increased expression of POLD1 was associated with shorter DFS at early-stage (P=0.037), late-stage cases (P=0.023) and with the presence of triple-negative tumors (TNBC; P=0.049). Multivariate analysis revealed that POLD1 may be used as an independent prognostic factor in patients with breast cancer. In vitro studies revealed that downregulation of POLD1 suppressed cell cycle progression and proliferation in MCF-7 cells. In conclusion, POLD1 may be considered as a potential prognostic marker for invasive breast carcinoma.

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