Potential tumor suppressor NESG1 as an unfavorable prognosis factor in nasopharyngeal carcinoma
Authors: Xiaoli Yu
Yajie Zhang
Yan Zhen
Yanfen Ye
Ying Zhou
Zhen Liu
Xin Li
Weiren Luo
Qinping Jiang
Hao Wang
Kaitai Yao
Weiyi Fang
Huiling Yang
Journal: PloS one (2011)
Discipline: Multidisciplinary
Keywords: NESG1; nasopharyngeal carcinoma; tumor suppressor; prognosis; cell proliferation
Affiliations: Department of Pathology, Basic School of Guangzhou Medical College, Guangzhou, People's Republic of China.

Abstract:  Background: Recently we identified nasopharyngeal epithelium specific protein 1 (NESG1) as a potential tumor suppressor in nasopharyngeal carcinoma (NPC). The purpose of this study is to investigate the involvement of NESG1 in tumor progression and prognosis of human NPC. Methodology/principal findings: NESG1 protein expression in NPC was examined. Survival analysis was performed using Kaplan-Meier method. The effect of NESG1 on cell proliferation, migration, and invasion were also investigated. Results: NESG1 expression was downregulated in atypical hyperplasia and NPC samples compared to normal and squamous nasopharynx tissues. Reduced protein expression was negatively associated with the status of NPC progression. Patients with lower NESG1 expression had a shorter overall survival and disease-free time than did patients with higher NESG1 expression. Multivariate analysis suggested NESG1 expression as an independent prognostic indicator for NPC patient survival. Proliferation, migration, and invasion ability were significantly increased in cell lines following lentiviral-mediated shRNA suppression of NESG1 expression. Microarray analysis indicated that NESG1 participated in multiple pathways, including MAPK signaling and cell cycle regulation. Finally, DNA methylation microarray examination revealed a lack of hypermethylation at the NESG1 promoter, suggesting other mechanisms are involved in suppressing NESG1 expression in NPC. Conclusion: Our studies are the first to demonstrate that decreased NESG1 expression is an unfavorable prognostic factor for NPC. 

Retracted: No

PubPeer comments:
 2020 Expression of Concern. https: journals.plos.org plosone article?id=10.1371 journal.pone.0231298 After publication of this article [1], concerns were raised about the identity of the cell lines used in part of the study, the representation of the western blot data, and the availability of the underlying data. Four of the eight nasopharyngeal carcinoma cell lines used in the western blot experiment shown in Fig 1A have been reported elsewhere to be possibly contaminated or misidentified (CNE1, CNE2, HONE1, and HNE1, see ICLAC Register of Misidentified Cell Lines (iclac.org databases cross-contaminations ) [2], Cellosaurus [3] and [4u20135]). These cell lines were not used in the functional and mechanism studies reported in the article. The corresponding author has provided STR profile reports for the 5-8F cells and the HONE1 cells (S1 File). The results reported in Figs 3u20135 in the article use a single cell line (2F4) or its subclones, limiting the generalizability of the findings as representative of nasopharyngeal cancer biology. 2F4 and Ctr-C6 were derived from 5-8F cells [6]. The authors provided clarification of the source and provenance of the cell lines used as follows: 5-8F, 6-10B, and SUNE1 are from stock kept at the Cancer Institute of Southern Medical University since 2003, originally obtained from Cancer Center, Sun Yat-sen University where these cell lines were generated [7, 8]. C666-1 [9] are from stock kept by the Cancer Institute of Southern Medical University since 2003, originally obtained from Cancer Center of Sun Yat-sen University. The C666-1 cell line was originally generated at the Chinese University of Hong Kong. CNE1 and CNE2 are from stock kept by the Cancer Institute of Southern Medical University since 1999. HONE1 and HNE1 are from stock kept by the Cancer Institute of Southern Medical University, originally obtained from the Cancer Institute of Hunan Medical University (now the Central Southern University) where these cell lines were generated. In the western blot shown in Fig 1A, there is a vertical discontinuity between lanes 5 and 6. The authors stated that lanes 1u20135 and lanes 6u20138 originate from different films. A longer exposure time was used for the film for the NPC samples compared to the film for the NP samples. The original uncropped blots underlying Fig 1 are no longer available. A revised Fig 1 is provided here in which the two films are shown on separate panels. In the NESG1-mediated pathways subsection of the Results, the incorrect reference is included in the in-text citations. The correct sentences cite Reference 9 of the original article, as follows: u201cWe recently observed 2408 differentially expressed genes between NESG1-overexpressing 2F4 cells and NESG1-negative Ctr-C6 cells (http: www.ncbi.nlm.nih.gov geo query acc.cgi?acc=GSE27318) by microarray analysis [9]. Further, NESG1-mediated differential expression of 1442 genes were used to conduct pathway analysis against the KEGG database, each with an u201c_atu201d extension in probe set IDs representing unique probe set sequences. Significant pathways 1u201310 are listed in Fig 5A (Table 4), which included cell cycle regulators that had been partially validated [9].u201d Reference 9 of the original article is: Liu Z, Li X, He X, Jiang Q, Xie S, et al. (2011) Decreased expression of updated NESG1 in nasopharyngeal carcinoma: Its potential role and preliminarily functional mechanism. Int J Cancer 128: 2562u20132571. The raw data for the NimbleGen DNA methylation microarray experiment reported in Fig 6 were not deposited in a public repository as required by the standards of the field. The dataset was subsequently deposited and is available at: https: datadryad.org stash dataset doi:10.5061 dryad.wh70rxwj1. No additional underlying dataset is available for this article. The PLOS ONE Editors issue an Expression of Concern to alert readers to the concerns about the accuracy of the representation of the western blot data and the use of cell lines previously reported to be misidentified. ,