Research Papers:

Combination of CALR and PDIA3 is a potential prognostic biomarker for non-small cell lung cancer

Ke Wang, Hao Li, Ruo Chen, Yang Zhang, Xiu-Xuan Sun, Wan Huang, Huijie Bian and Zhi-Nan Chen _

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Oncotarget. 2017; 8:96945-96957. https://doi.org/10.18632/oncotarget.18547

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Ke Wang1,*, Hao Li1,*, Ruo Chen1,2,*, Yang Zhang1,*, Xiu-Xuan Sun1, Wan Huang1, Huijie Bian1 and Zhi-Nan Chen1

1Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, P.R. China

2Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, P.R. China

*These authors have contributed equally to this work

Correspondence to:

Zhi-Nan Chen, email: [email protected]

Huijie Bian, email: [email protected]

Wan Huang, email: [email protected]

Keywords: CALR, PDIA3, non-small cell lung cancer, biomarker, proteomics

Received: March 02, 2017     Accepted: June 04, 2017     Published: June 16, 2017


Proteomic-based approaches for biomarker discovery are promising strategies used in cancer research. In this study, we performed quantitative proteomic analysis on 16 paired samples of non-small cell lung cancer (NSCLC) and adjacent non-tumor lung tissues using label-free quantitative proteomics and liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS) to identify differentially expressed proteins. A total of 91 proteins were differentially expressed in NSCLC compared with adjacent non-tumor lung tissues among 4047 identified proteins (fold change > 1.5 or < 0.67, P < 0.05). Gene ontology (GO) analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and ingenuity pathway analysis (IPA) of 91 dysregulated proteins showed that they were related to the cancer-associated biological processes. We confirmed that the candidate proteins, calreticulin (CALR) and protein disulfide isomerase family A member 3 (PDIA3) were overexpressed in NSCLC by real-time PCR using 20 paired samples and western blot using 5 paired samples. PDIA3 expression was highly associated with CALR expression (Spearman r = 0.345, P = 0.001) and they were co-localized and interacted with each other in A549 and H460 cells. Moreover, survival analysis performed in tissue microarray with 88 samples indicated that low expression of both CALR and PDIA3 in NSCLC was positively associated with poor overall survival. Combination of CALR and PDIA3 might serve as an efficient biomarker and improved the prediction of NSCLC prognosis significantly (P = 0.023). Our results collectively provide a potential biomarker dataset for NSCLC prognosis, especially the prognostic value of combined expression of CALR and PDIA3.

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