title: The Expression and Clinical Outcome of pCHK2-Thr68 and pCDC25C-Ser216 in Breast Cancer.
abstract: Checkpoint kinase 2 (CHK2) and cell division cycle 25C (CDC25C) are two proteins involved in the DNA damage response pathway, playing essential roles in maintaining genome integrity. As one of the major hallmarks of abnormal cellular division, genomic instability occurs in most cancers. In this study, we identified the functional expression of pCHK2-Thr68 and pCDC25C-Ser216 in breast cancer, as well as its association with breast cancer survival. Tissue microarray analysis using immunohistochemistry was constructed to identify the expression of pCHK2-Thr68 and pCDC25C-Ser216 in 292 female breast cancer patients. The relationship among protein expression, clinicopathological factors (e.g., human epidermal growth factor receptor 2 (HER 2), tumor size, tumor-node-metastasis (TNM) classification), and overall survival of the breast cancer tissues were analyzed using Pearson's χ-square (χ²) test, Fisher's exact test, multivariate logistic regression and Kaplan-Meier survival analysis. Significantly higher expressions of pCHK2-Thr68 and pCDC25C-Ser216 were observed in the nucleus of the breast cancer cells compared to the paracancerous tissue (pCHK2-Thr68, 20.38% vs. 0%; pCDC25C-Ser216, 82.26% vs. 24.24%). The expression of pCHK2-Thr68 and pCDC25C-Ser216 in breast cancer showed a positive linear correlation (p= 0.026). High expression of pCHK2-Thr68 was associated with decreased patient survival (p= 0.001), but was not an independent prognostic factor. Our results suggest that pCHK2-Thr68 and pCDC25C-Ser216 play important roles in breast cancer and may be potential treatment targets.
authors: Department of Radiation Oncology, PLA Army General Hospital, Beijing 100700, China. doctorjhy@163.com.
authors: Huayong
authors: H
authors: Jiang
authors: Department of Oncology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China. qcwangb@163.com.
authors: Bin
authors: B
authors: Wang
authors: Department of Radiation Oncology, PLA Army General Hospital, Beijing 100700, China. radiozfli@163.com.
authors: Fuli
authors: F
authors: Zhang
authors: Department of Emergency, Chinese PLA General Hospital, Beijing 100853, China. qyy301@sina.com.
authors: Yuanyu
authors: Y
authors: Qian
authors: Radiologic Sciences and Respiratory Therapy Division, School of Health and Rehabilitation Sciences, The Ohio State University College of Medicine, Columbus, OH 43210, USA. chuang.107@osu.edu.
authors: Chia-Chen
authors: CC
authors: Chuang
authors: Department of Oncology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China. yingmz@163.com.
authors: Mingzhen
authors: M
authors: Ying
authors: Department of Oncology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China. yajiewangch@163.com.
authors: Yajie
authors: Y
authors: Wang
authors: Radiologic Sciences and Respiratory Therapy Division, School of Health and Rehabilitation Sciences, The Ohio State University College of Medicine, Columbus, OH 43210, USA. zuo.4@osu.edu.
authors: Li
authors: L
authors: Zuo
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D064447:Checkpoint Kinase 2 / Q000096:biosynthesis* / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D046228:Microarray Analysis; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D020687:cdc25 Phosphatases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D064447:Checkpoint Kinase 2; D018719:Erb-b2 Receptor Tyrosine Kinases; D020687:cdc25 Phosphatases; C508053:ERBB2 protein, human; C578634:CHEK2 protein, human; C517009:CDC25C protein, human
keywords: breast cancer; genomic instability; immunohistochemistry; pCDC25C-Ser216; pCHK2-Thr68