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Increased expression of TMED2 is an unfavorable prognostic factor in patients with breast cancer

Authors Lin X, Liu J, Hu SF, Hu X

Received 31 October 2018

Accepted for publication 19 February 2019

Published 18 March 2019 Volume 2019:11 Pages 2203—2214

DOI https://doi.org/10.2147/CMAR.S192949

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Antonella D'Anneo


Xia Lin,1 Jian Liu,2 Shu Fang Hu,2 Xun Hu1

1Cancer Institute (a Key Laboratory for Cancer Prevention & Intervention, China National Ministry of Education), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2The Department of Breast Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China

Background: We obtained 2 types of clones which were termed SC (sphere-shaped clone) and NSC (non-sphere-shaped clone) from 4T1 cells by monoclonal culture. SC and NSC were distinct in morphology, surface marker, metabolism and proliferation rate. With the transcriptome sequencing data analysis, we found TMED2 expressed higher in SCs. TMED2 was a member of the transmembrane emp24 domain and might play roles in cancer cell proliferation. However, its prognostic roles in breast cancer remained unknown. We aimed to investigate the prognostic values of TMED2 in patients with breast cancer.
Methods: We used UALCAN (http://ualcan.path.uab.edu) and the Human Protein Atlas (www.proteinatlas.org) to explore the TMED2 expression level and DNA methylation data between breast cancer and normal breast tissue. With Oncomine (www.oncomine.org), we investigated the copy number of TMED2 in breast cancer sample and normal breast tissue. We used the Kaplan–Meier Plotter database (http://kmplot.com/analysis) to analyze prognostic values of TMED2 mRNA expression in all breast cancers and in different intrinsic subtypes. Moreover, protein expression levels of TMED2 were confirmed by Western blot in breast cancer tissues and normal mammary tissue as well as SCs and NSCs.
Results: TMED2 significantly upregulated in breast cancer patients compared to normal mammary samples. Meanwhile, the increased expression of TMED2 mRNA was closely associated with reduced overall survival (OS) in all breast cancers, and with reduced OS in patients with ER-positive, Luminal A or Luminal B breast cancer subtypes. Moreover, western blot confirmed that TMED2 increased expressed was correlated with the reduced OS at protein levels.
Conclusion: Increased expression of TMED2 was significantly related to unfavorable outcomes in patients with breast cancer. Thus, we supposed TMED2 is oncogenic and a potential target for breast cancer therapy and these preliminary findings require further study to determine whether TMED2-targeting reagents might be developed for clinical application in breast cancer.

Keywords: breast cancer, SC, NSC, TMED2, overall survival, KM plotter

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