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

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.

Dual Antimicrobial and Antiproliferative Activity of TcPaSK Peptide Derived from a Tribolium castaneum Insect Defensin

“…All of them were found to be present in MDA-MB-231 cells when searched in the proteomic landscape of TNBC database ( ; [ 37 ]), as well as in other different types of tumor tissues when searched in the human protein atlas database ( ; [ 38 ]). Moreover, the overexpression of several of these proteins has been specifically correlated with disease progression and adverse prognosis as with La-related protein 1 (LARP1) in cervical and non-small cell lung cancers [ 39 ], density-regulated protein (DENR) in hepatocellular carcinoma, gastric cancer, kidney cancer, laryngeal cancer and lung cancer [ 40 ], U2AF2 splicing factor in prostate cancer [ 41 ], adenylate kinase 2 (AK2) protein in pulmonary adenocarcinoma [ 42 ], DNA polymerase delta catalytic subunit in breast cancer (POLD1) in breast cancer [ 43 ], endophilin A in basal-like breast cancers [ 44 ], thioredoxin reductase (TRXR1) in hepatocellular carcinoma [ 45 ], matrix metalloproteinase 14 (MMP14) in colorectal cancer [ 46 ] and gluthatione peroxidase 1 (GPX1) in oral squamous cell carcinoma [ 47 ].…”

Integrated WGCNA and PPI Network to Screen Hub Genes Signatures for Infantile Hemangioma

“…POLD1 is involved in controlling DNA repair and has been shown to be associated with cancer ( Nicolas et al, 2016 ). High expression of POLD1 may serve as a potential prognostic indicator for invasive breast cancer ( Qin et al, 2018 ). The cell cycle gene RAD54L may be inhibited by p53 to regulate G2/M cell cycle ( Fischer et al, 2016 ).…”

The identification of six risk genes for ovarian cancer platinum response based on global network algorithm and verification analysis

“…It was proposed that POLD1 was directly or indirectly related to platinum resistance in mesothelioma 72 . It has been reported that POLD1 is expressed in a variety of tumour cells, such as breast cancer, 73 hepatocellular carcinoma, 74 head and neck cell cancer 75 and cervical cancer 76 . As for oesophageal squamous cell carcinoma, POLD1 mediated the chemical resistance to cisplatin through the regulation of HSP90/ERK signalling 77 …”