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Proteomic profiling of lung adenocarcinoma indicates heightened DNA repair, antioxidant mechanisms and identifies LASP1 as a potential negative predictor of survival

Overview of attention for article published in Clinical Proteomics, October 2016
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3 tweeters

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Title
Proteomic profiling of lung adenocarcinoma indicates heightened DNA repair, antioxidant mechanisms and identifies LASP1 as a potential negative predictor of survival
Published in
Clinical Proteomics, October 2016
DOI 10.1186/s12014-016-9132-y
Pubmed ID
Authors

Johannes F. Fahrmann, Dmitry Grapov, Brett S. Phinney, Carol Stroble, Brian C. DeFelice, William Rom, David R. Gandara, Yanhong Zhang, Oliver Fiehn, Harvey Pass, Suzanne Miyamoto

Abstract

Lung cancer is the leading cause of cancer mortality in the United States. Non-small cell lung cancer accounts for 85% of all lung cancers for which adenocarcinoma is the most common histological type. Management of lung cancer is hindered by high false-positive rates due to difficulty resolving between benign and malignant tumors. Better molecular analysis comparing malignant and non-malignant tissues will provide important evidence of the underlying biology contributing to tumorigenesis. We utilized a proteomics approach to analyze 38 malignant and non-malignant paired tissue samples obtained from current or former smokers with early stage (Stage IA/IB) lung adenocarcinoma. Statistical mixed effects modeling and orthogonal partial least squares discriminant analysis were used to identify key cancer-associated perturbations in the adenocarcinoma proteome. Identified proteins were subsequently assessed against clinicopathological variables. Top cancer-associated protein alterations were characterized by: (1) elevations in APEX1, HYOU1 and PDIA4, indicative of increased DNA repair machinery and heightened anti-oxidant defense mechanisms; (2) increased LRPPRC, STOML2, COPG1 and EPRS, suggesting altered tumor metabolism and inflammation; (3) reductions in SPTB, SPTA1 and ANK1 implying dysregulation of membrane integrity; and (4) decreased SLCA41 suggesting altered pH regulation. Increased protein levels of HYOU1, EPRS and LASP1 in NSCLC adenocarcinoma was independently validated by tissue microarray immunohistochemistry. Immunohistochemistry for HYOU1 and EPRS indicated AUCs of 0.952 and 0.841, respectively, for classifying tissue as malignant. Increased LASP1 correlated with poor overall survival (HR 3.66 per unit increase; CI 1.37-9.78; p = 0.01). These results reveal distinct proteomic changes associated with early stage lung adenocarcinoma that may be useful prognostic indicators and therapeutic targets.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 3%
Unknown 37 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 26%
Researcher 6 16%
Student > Master 5 13%
Student > Postgraduate 4 11%
Professor 3 8%
Other 4 11%
Unknown 6 16%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 8 21%
Medicine and Dentistry 6 16%
Agricultural and Biological Sciences 5 13%
Computer Science 4 11%
Chemistry 2 5%
Other 6 16%
Unknown 7 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 November 2016.
All research outputs
#7,831,016
of 12,480,234 outputs
Outputs from Clinical Proteomics
#90
of 156 outputs
Outputs of similar age
#158,056
of 282,518 outputs
Outputs of similar age from Clinical Proteomics
#22
of 32 outputs
Altmetric has tracked 12,480,234 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 156 research outputs from this source. They receive a mean Attention Score of 4.2. This one is in the 30th percentile – i.e., 30% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 282,518 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 34th percentile – i.e., 34% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 32 others from the same source and published within six weeks on either side of this one. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.