Glycine decarboxylase and HIF-1α expression are negative prognostic factors in primary resected early-stage non-small cell lung cancer.

Details

Serval ID
serval:BIB_20417420E360
Type
Article: article from journal or magazin.
Collection
Publications
Title
Glycine decarboxylase and HIF-1α expression are negative prognostic factors in primary resected early-stage non-small cell lung cancer.
Journal
Virchows Archiv
Author(s)
Berezowska S., Galván J.A., Langer R., Bubendorf L., Savic S., Gugger M., Schmid R.A., Marti T.M.
ISSN
1432-2307 (Electronic)
ISSN-L
0945-6317
Publication state
Published
Issued date
03/2017
Peer-reviewed
Oui
Volume
470
Number
3
Pages
323-330
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Glycine decarboxylase (GLDC) was recently described as a critical enzyme of tumor-initiating cells and, thus, a driver of tumorigenesis in lung non-small cell cancer (NSCC). It is important in metabolism under hypoxic conditions. Hypoxia-inducible factor 1-alpha (HIF-1α) is the unique subunit that determines HIF system activity, thereby regulating the adverse effects of hypoxia on cancer outcome. We examined the expression and prognostic significance of GLDC and HIF-1α in primary resected stage I/II NSCC. Immunohistochemistry for GLDC and HIF-1α was validated on two lung NSCC cell lines (A549, NCI-H460) and evaluated on a tissue microarray with 428 lung NSCC: 184 adenocarcinomas, 211 squamous cell carcinomas, and 33 large cell carcinomas (LCC). The results were correlated with clinico-pathological parameters. High levels of GLDC expression were detected in 33/428 cases (7.7%). HIF-1α was expressed in 71 (16.6%) cases and more frequently in squamous cell carcinoma (p < 0.001). Significantly longer survival was seen in younger patients (p = 0.007), patients with non-LCC histology (p = 0.006), lower primary tumor category (p = 0.002), and Union for International Cancer Control (UICC) stage (p = 0.001). Both GLDC and HIF-1α were significantly associated with worse tumor-related survival (p = 0.013, p = 0.021, respectively), although not independent from each other in multivariate models. The combination of low-GLDC/negative HIF-1α expression was significantly prognostic for longer survival (p = 0.002) and emerged as an independent prognostic factor in multivariate analysis (p = 0.007, HR 2.052), next to UICC stage and age. We show that the combination of GLDC and HIF-1α expression is an independent prognostic factor in early-stage NSCC. Our results will assist future development of therapeutic approaches targeting GLDC or exploiting tumor hypoxia.
Keywords
Adult, Aged, Aged, 80 and over, Biomarkers, Tumor/analysis, Carcinoma, Non-Small-Cell Lung/metabolism, Carcinoma, Non-Small-Cell Lung/mortality, Carcinoma, Non-Small-Cell Lung/pathology, Disease-Free Survival, Female, Glycine Dehydrogenase (Decarboxylating)/analysis, Glycine Dehydrogenase (Decarboxylating)/biosynthesis, Humans, Hypoxia-Inducible Factor 1, alpha Subunit/analysis, Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis, Immunohistochemistry, Kaplan-Meier Estimate, Lung Neoplasms/metabolism, Lung Neoplasms/mortality, Lung Neoplasms/pathology, Male, Middle Aged, Prognosis, Proportional Hazards Models, Tissue Array Analysis, Glycine decarboxylase, HIF-1α, Hypoxia, NSCC
Pubmed
Web of science
Create date
29/06/2020 10:44
Last modification date
30/06/2020 5:26
Usage data