Open AccessDifferentially expressed and survival‐related proteins of lung adenocarcinoma with bone metastasis
Author(s) -
Yang Mengdi,
Sun Yi,
Sun Jing,
Wang Zhiyu,
Zhou Yiyi,
Yao Guangyu,
Gu Yifeng,
Zhang Huizhen,
Zhao Hui
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1363
Subject(s) - adenocarcinoma , immunohistochemistry , biology , nucleoside diphosphate kinase , metastasis , log rank test , survival analysis , staining , biomarker , enolase , pathology , cancer research , microbiology and biotechnology , medicine , cancer , gene , immunology , genetics
Abstract Despite recent advances in targeted and immune‐based therapies, the poor prognosis of lung adenocarcinoma ( LUAD ) with bone metastasis ( BM ) remains a challenge. First, two‐dimensional gel electrophoresis (2‐ DE ) was used to identify proteins that were differentially expressed in LUAD with BM , and then matrix‐assisted laser desorption/ionization time of flight mass spectrometry ( MALDI ‐ TOF ‐ MS ) was used to identify these proteins. Second, the Cancer Genome Atlas ( TCGA ) was used to identify mutations in these differentially expressed proteins and Kaplan–Meier plotter ( KM Plotter) was used to generate survival curves for the analyzed cases. Immunohistochemistry ( IHC ) was used to check the expression of proteins in 28 patients with BM and nine patients with LUAD . Lastly, the results were analyzed with respect to clinical features and patient's follow‐up. We identified a number of matched proteins from 2‐ DE . High expression of enolase 1 ( ENO 1) ( HR = 1.67, logrank P = 1.9E‐05), ribosomal protein lateral stalk subunit P2 ( RPLP 2) ( HR = 1.77, logrank P = 2.9e‐06), and NME / NM 23 nucleoside diphosphate kinase 2 ( NME 1‐ NME 2) ( HR = 2.65, logrank P = 3.9E‐15) was all significantly associated with poor survival ( P < 0.05). Further, ENO 1 was upregulated ( P = 0.0004) and calcyphosine ( CAPS 1 ) was downregulated ( P = 5.34E‐07) in TCGA LUAD RNA ‐seq expression data. IHC revealed that prominent ENO 1 staining ( OR = 7.5, P = 0.034) and low levels of CAPS 1 ( OR = 0.01, P < 0.0001) staining were associated with BM incidence. Finally, we found that LUAD patients with high expression of ENO 1 and RPLP 2 had worse overall survival. This is the first instance where the genes ENO1 , RPLP2 , NME1‐NME2 and CAPS1 were associated with disease severity and progression in LUAD patients with BM. Thus, with this study, we have identified potential biomarkers and therapeutic targets for this disease.