UBE2D1 RNA Expression Was an Independent Unfavorable Prognostic Indicator in Lung Adenocarcinoma, but Not in Lung Squamous Cell Carcinoma

Yingbo Li,Liyan Hou,Ying Cong,Dongqiang Xu,Ying Wang,Hailing Cui,Chengyong Yu,Xiaoyan Xu

doi:10.1155/2018/4108919

Yingbo Li, Liyan Hou + Show 6 more

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https://doi.org/10.1155/2018/4108919

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Journal: Disease Markers	Publication Date: Oct 21, 2018
Citations: 17	License type: CC BY 4.0

Affiliation: Weinan Central Hospital, Weihai Chest Hospital

Abstract

In this study, we investigated the potential prognostic value of ubiquitin-conjugating enzyme E2D1 (UBE2D1) RNA expression in different histological subtypes of non-small-cell lung cancer (NSCLC). A retrospective study was performed by using molecular, clinicopathological, and survival data in the Cancer Genome Atlas (TCGA)—Lung Cancer. Results showed that both lung adenocarcinoma (LUAD) (N = 514) and lung squamous cell carcinoma (LUSC) (N = 502) tissues had significantly elevated UBE2D1 RNA expression compared to the normal tissues (p < 0.001 and p = 0.036, respectively). UBE2D1 RNA expression was significantly higher in LUAD than in LUSC tissues. Increased UBE2D1 RNA expression was independently associated with shorter OS (HR: 1.359, 95% CI: 1.031–1.791, p = 0.029) and RFS (HR: 1.842, 95% CI: 1.353–2.508, p < 0.001) in LUAD patients, but not in LUSC patients. DNA amplification was common in LUAD patients (88/551, 16.0%) and was associated with significantly upregulated UBE2D1 RNA expression. Based on these findings, we infer that UBE2D1 RNA expression might only serve as an independent prognostic indicator of unfavorable OS and RFS in LUAD, but not in LUSC.

Highlights

Ubiquitination is a biological process, in which the targeting proteins were modified with ubiquitin for degradation [1]
The comparison showed that both lung adenocarcinoma (LUAD) (N = 514) and lung squamous cell carcinoma (LUSC) (N = 502) tissues had significantly elevated ubiquitin-conjugating enzyme E2D1 (UBE2D1) RNA expression compared to the normal tissues (p < 0 001 and p = 0 036, Figures 1(a)–1(d))
LUAD tissues had substantially higher expression of UBE2D1 RNA expression compared to LUSC tissues (p < 0 001, Figure 1(e))

Summary

Introduction

Ubiquitination is a biological process, in which the targeting proteins were modified with ubiquitin for degradation [1]. E2s mediate ubiquitination by selective interactions with E1s and E3s and are responsible for the E3 selection and substrate modification, playing a critical role in ubiquitin transfer [3, 4] They dictate the synthesis of a mono- or polyubiquitinated chain of a specific lysine linkage, which subsequently determines the fate of the substrate: proteasomal degradation or signaling [3, 4]. Previous studies found that UBE2D dysregulation is involved in some important pathways in carcinogenesis They mediate the ubiquitination of the tumor-suppressor protein p53 [7,8,9]. UBE2D1 can collaborate with cellular inhibitor of apoptosis protein 1 (cIAP1) and mediate tumor necrosis factor α- (TNFα-) stimulated receptor-interacting protein 1 (RIP1) ubiquitination and NF-kappaB activation [11]. One recent study found that Smad ubiquitination regulatory factor 2 (SMURF2)

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