ADAM28: A potential oncogene involved in asbestos‐related lung adenocarcinomas

Abstract

Asbestos-related lung cancer accounts for 4-12% of all lung cancers worldwide. Since putative mechanisms of carcinogenesis differ between asbestos and tobacco induced lung cancers, tumors induced by the two agents may be genetically distinct. To identify gene expression biomarkers associated with asbestos-related lung tumorigenicity we performed gene expression array analysis on tumors of 36 patients with primary lung adenocarcinoma, comparing 12 patients with lung asbestos body counts above levels associated with urban dwelling (ARLC-AC: asbestos-related lung cancer-adenocarcinoma) with 24 patients with no asbestos bodies (NARLC-AC: non-asbestos related lung cancer-adenocarcinoma). Genes differentially expressed between ARLC-AC and NARLC-AC were identified on fold change and P value, and then prioritized using gene ontology. Candidates included ZNRF3, ADAM28, PPP1CA, IRF6, RAB3D, and PRDX1. Expression of these six genes was technically and biologically replicated by qRT-PCR in the training set and biologically validated in three independent test sets. ADAM28, encoding a disintegrin and metalloproteinase domain protein that interacts with integrins, was consistently upregulated in ARLC across all four datasets. Further studies are being designed to investigate the possible role of this gene in asbestos lung tumorigenicity, its potential utility as a marker of asbestos related lung cancer for purposes of causal attribution, and its potential as a treatment target for lung cancers arising in asbestos exposed persons.

MicroRNA-552 enhances metastatic capacity of colorectal cancer cells by targeting a disintegrin and metalloprotease 28

“…Intriguingly, such an evoked expression of ADAM28 was also found in the patients with recurrent NSCLC and/or lymph node metastasis, and was correlated with a poor disease-free survival [19]. In asbestos-related lung adenocarcinomas, however the expression of ADAM28 was even more elevated than non-asbestos related lung cancer adenocarcinoma [18]. Equally noteworthy, the level of ADAM28 in sera of advanced NSCLC patients was declined during a chemotherapeutic process, and was significantly correlated with the therapeutic responses and prognosis, indicating that the serum ADAM28 may be a reliable surrogate marker for predicting tumor response to a chemotherapeutic regimen and the survival in patients with advanced NSCLC [17].…”

Integrative Analysis of Gene Networks and Their Application to Lung Adenocarcinoma Studies

“…This approach enables us to partially use the information from each source for each edge, which could not be achieved by the penalty-based joint estimation methods because it requires a complete design matrix from all sources. For example, for GAPDH and ANKRD46 genes, there are many missing values in some data sets, 28,29,34,36 but there are no missing values in other data sets. Although the ψ z -scores in equation (2) cannot be computed in the data sets with missing values, the combined ψ z -score for the relationship between GAPDH and ANKRD46 can be obtained by combining the ψ z -scores from other sources, where the corresponding weights $w_{ij}^{(k)}$ for data sets with missing values are set to zero in equation (4).…”

Molecular Fingerprints of Environmental Carcinogens in Human Cancer

“…In asbestos-related tumors [87], through gene expression array analysis on tumors of 36 patients with primary lung adenocarcinoma (12 patients with lung asbestos body counts higher than levels associated with urban dwelling with 24 patients with no asbestos bodies), found an mRNA up-regulation of ADAM 28, which encodes a disintegrin and metalloproteinase domain protein that interacts with integrins. The same carcinogens also determine an mRNA overexpression of Annexin 2 in lung cancer and normal tissue of asbestosexposed patients [88].…”