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Mo et al. Cancer Cell Int (2017) 17:83 DOI 10.1186/s1***-1 Cancer Cell International PRIMARY RESEARCH Open Access The clinicopathological significance of UBE2C in breast cancer: a study based on immunohistochemistry, microarray and RNA sequencing data Chao hua Mo1†, Li Gao1†, Xiao fei Zhu1,2, Kang lai Wei1, Jing jing Zeng1, Gang Chen1*‡ and Zhen bo Feng1*‡ Abstract  Background:  Ubiquitin-conjugating enzyme E2C (UBE2C) has been previously reported to correlate with the malig  nant progression of various human cancers, however, the exact molecular function of UBE2C in breast carcinoma (BRCA) remained elusive. We aimed to investigate UBE2C expression in BRCA and its clinical significance. Methods:  The expression of UBE2C in 209 BRCA tissue samples and 53 adjacent normal tissue samples was detected using immunohistochemistry. The clinical role of UBE2C was analyzed. Public databases including the human protein atlas and Oncomine were used to assess UBE2C expression in BRCA. Moreover, the cancer genome atlas (TCGA) data  base was employed to investigate the prognostic value of UBE2C in BRCA. Results:  The positive expression rate of UBE2C in BRCA was 70.8% (148/209), and UBE2C expression in the adjacent breast tissue was negative. The expression of UBE2C was positively correlated with tumor size (r = 0.32, P < 0.001), histological grade (r = 0.237, P = 0.001), clinical stage (r = 0.198, P = 0.004), lymph node metastasis (r = 0.155, P = 0.026), HER2 expression level (r = 0.356, P < 0.001), Ki-67 expression level (r = 0.504, P < 0.001), and P53 expres  sion level (r = 0.32, P = 0.001). Negative correlations were found between UBE2C expression and the ER (r = − 0.403, P < 0.001) and PR (r = − 0.468, P < 0.001) status. UBE2C gene expression data from the public databases all proved that UBE2C was overexpressed in BRCA. According to the TCGA data analysis, a higher positive expression of UBE2C was associated with worse survival of BRCA patients (P = 0.0428), and data from cBioPortal indicated that 11% of all sequenced BRCA patients possessed a gene alteration of UBE2C, predominately gene amplification and mRNA regulation. Conclusion:  Ubiquitin-conjugating enzyme E2C might pose an oncogenic effect on the progression of BRCA. Keywords:  Breast cancer, Ubiquitin-conjugating enzyme E2C, Immunohistochemistry, Public database, Clinico-pathological significance, Gene alteration *Correspondence: chen_gang_triones@163.com; guanghu1963@126.com †Chao-hua Mo and Li Gao contributed equally as first authors ‡Gang Chen and Zhen-bo Feng contributed equally as corresponding authors 1 Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China Full list of author information is available at the end of the article © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Mo et al. Cancer Cell Int (2017) 17:83 Page 2 of 17 Background Breast carcinoma (BRCA) is one of the most common malignant neoplasms in humans and has a high cancerrelated morbidity in females, ranking 6th in mortality for females [1]. BRCA is a highly heterogeneous neoplasm [2], and the mechanism underlying its initiation and development remains unclear. Therefore, the identification of biomarkers for early diagnosis, prognosis judgment and treatment of BRCA is urgently needed. Ubiquitin-conjugating enzyme E2C (UBE2C), a crucial part of the ubiquitin-conjugating enzyme complex, is involved in the ubiquitin–proteasome system. The ubiquitin–proteasome pathway is one of the main pathways of protein degradation in eukaryotes and serves as an important component in the post-translational modification of proteins. The process of ubiquitination is associated with many biological processes [3–6]. In recent studies, the dysregulation of the ubiquitination process has been discovered to play essential roles in the occurrence and progression of cancers, and ubiquitination has, thus, become a new therapeutic target for cancer [7–9]. Previous studies have reported overexpression of UBE2C in some cancers such as colorectal carcinoma [10], pancreatic carcinoma [11], cervical cancer [12], bladder carcinoma [13], esophageal squamous cell carcinoma [9] and lung cancer, etc. [14]. Particularly, cancers with a high degree of malignancy, low differentiation and high metastatic tendency usually present with higher UBE2C expression and poor patient survival [3]. Although several studies have confirmed UBE2C overexpression in BRCA and the prognostic significance of UBE2C in BRCA [8, 15–17], the specific role and molecular mechanism of UBE2C expression in BRCA is unclear. Therefore, in this study, we employed immunohistochemistry (IHC) and bioinformatics analysis guided by public databases containing data on gene expression in cancer to detect UBE2C expression in BRCA and adjacent tissues. Moreover, we investigated the clinico-pathological significance of UBE2C expression in BRCA and endeavored to elucidate the molecular mechanism underlying it. Materials and methods IHC Patient population We collected archived wax blocks of 209 pathologically diagnosed infiltrating ductal breast carcinoma tissues and 53 corresponding adjacent tissues that were 5 cm away from the tumor edges in Liuzhou Worker’s Hospital during the period of January 2013 to March 2015. All of the patients were females ranging from 31 to 81 years old with a median age of 50 years. The clinico-pathological information of the 209 infiltrating ductal carcinoma tissue samples is listed in Table 1. Study protocol was approved by The Table /1 Clinico-pathological features of the 209 cases of infiltrating ductal breast carcinoma tissues Clinico-pathological variables Group Number (%) Age (year) Histological grade Pathological stage (PTNM) Tumor size (cm) Lymph node metastasis Distant metastasis Clinical stage Molecular types ≤ 50 > 50 I II III I–II III–IV ≤2 2–5 >5 N0 N1 N2 N3 M0 M1 I II III IV Luminal A Luminal B (HER2−) Luminal B (HER2+) HER2 overexpression Triple-negative 110 (52.6) 99 (47.4) 18 (8.6) 97 (46.4) 94 (45.0) 145 (69.4) 64 (30.6) 57 (27.3) 131 (62.7) 21 (10.0) 104 (49.3) 54 (25.8) 22 (10.5) 29 (13.9) 204 (97.6) 5 (2.4) 23 (11.0) 122 (58.4) 59 (28.2) 5 (2.4) 62 (29.7) 33 (15.8) 33 (15.8) 42 (20.1) 39 (18.7) Ethical Committee of First Affiliated Hospital of Guangxi Medical University. All the patients signed the written informed consents before participating in the study. Major reagent The rabbit anti-human monoclonal antibody against UBE2C (1:100 dilution) was purchased from the Abnova Co., ltd. Fast enzyme-labeled Goat anti-mouse/rabbit IgG polymer, citrate buffer, phosphate buffer saline (PBS) and diaminobenzidine (DAB) indicator were all purchased from Fuzhou Maixin Biotechnology Development Co., ltd. Apart from the rabbit anti-human monoclonal antibody against UBE2C, the following antibodies were used in IHC: rabbit anti-human HER2 monoclonal antibody (EP3, Fuzhou Maixin Biotechnology Development Co., ltd), rabbit anti-human P53 monoclonal antibody (SP5, Fuzhou Maixin Biotechnology Development Co., ltd), rabbit anti-human ER monoclonal antibody (SP1, Fuzhou Maixin Biotechnology Development Co., ltd), rabbit anti-human PR monoclonal antibody (SP2, Fuzhou Maixin Biotechnology Development Co., ltd) and mouse anti-human Ki67 monoclonal antibody (MIB-1, Fuzhou Mo et al. Cancer Cell Int (2017) 17:83 Pag 内容过长，仅展示头部和尾部部分文字预览，全文请查看图片预览。 east cancer. Oncol Rep. 2015;34:877–83. doi:10.3892/ or.2015.4049. Submit your next manuscript to BioMed Central and we will help you at every step: • We accept pre-submission inquiries • Our selector tool helps you to ?nd the most relevant journal • We provide round the clock customer support • Convenient online submission • Thorough peer review • Inclusion in PubMed and all major indexing services • Maximum visibility for your research Submit your manuscript at doc.001pp.com/submit [文章尾部最后500字内容到此结束,中间部分内容请查看底下的图片预览]请点击下方选择您需要的文档下载。

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