Abnormal levels of heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in tumour tissue and blood samples from patients diagnosed with lung cancer

被引:26
|
作者
Dowling, Paul [1 ,2 ]
Pollard, Damian [1 ]
Larkin, AnneMarie [1 ]
Henry, Michael [1 ]
Meleady, Paula [1 ]
Gately, Kathy [2 ]
O'Byrne, Kenneth [3 ]
Barr, Martin P. [3 ]
Lynch, Vincent [1 ]
Ballot, Jo [4 ,5 ]
Crown, John [4 ,5 ]
Moriarty, Michael [1 ]
O'Brien, Emmet [4 ,5 ]
Morgan, Ross [6 ]
Clynes, Martin [1 ]
机构
[1] Dublin City Univ, Natl Inst Cellular Biotechnol, Dublin 9, Ireland
[2] Natl Univ Ireland, Dept Biol, Maynooth, Kildare, Ireland
[3] Univ Dublin Trinity Coll, St James Hosp, Trinity Ctr Hlth Sci, Inst Mol Med, Dublin 2, Ireland
[4] MTCI, Dublin, Ireland
[5] St Vincents Univ Hosp, Dublin 4, Ireland
[6] Beaumont Hosp, Dept Resp Med, Dublin 9, Ireland
关键词
M2; PYRUVATE-KINASE; HSP70-INTERACTING PROTEIN CHIP; SQUAMOUS-CELL CARCINOMA; LACTATE-DEHYDROGENASE; PROTEOMICS; A2/B1; EXPRESSION; BIOMARKER; BREAST; MARKER;
D O I
10.1039/c4mb00384e
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Lung cancer is the second most common type of cancer in the world and is the most common cause of cancer-related death in both men and women. Research into causes, prevention and treatment of lung cancer is ongoing and much progress has been made recently in these areas, however survival rates have not significantly improved. Therefore, it is essential to develop biomarkers for early diagnosis of lung cancer, prediction of metastasis and evaluation of treatment efficiency, as well as using these molecules to provide some understanding about tumour biology and translate highly promising findings in basic science research to clinical application. In this investigation, two-dimensional difference gel electrophoresis and mass spectrometry were initially used to analyse conditioned media from a panel of lung cancer and normal bronchial epithelial cell lines. Significant proteins were identified with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), pyruvate kinase M2 isoform (PKM2), Hsc-70 interacting protein and lactate dehydrogenase A (LDHA) selected for analysis in serum from healthy individuals and lung cancer patients. hnRNPA2B1, PKM2 and LDHA were found to be statistically significant in all comparisons. Tissue analysis and knockdown of hnRNPA2B1 using siRNA subsequently demonstrated both the overexpression and potential role for this molecule in lung tumorigenesis. The data presented highlights a number of in vitro derived candidate biomarkers subsequently verified in patient samples and also provides some insight into their roles in the complex intracellular mechanisms associated with tumour progression.
引用
收藏
页码:743 / 752
页数:10
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