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

Berezowska, Sabina Anna; Galván Hernández, José Alberto; Langer, Rupert; Bubendorf, Lukas; Savic, Spasenija; Gugger, Mathias; Schmid, Ralph; Marti, Thomas (2017). Glycine decarboxylase and HIF-1α expression are negative prognostic factors in primary resected early-stage non-small cell lung cancer. Virchows Archiv, 470(3), pp. 323-330. Springer 10.1007/s00428-016-2057-z

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Thoracic Surgery
04 Faculty of Medicine > Other Institutions > Teaching Staff, Faculty of Medicine
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Thoraxchirurgie
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Services > Core Facility Zytometrie-Labor/FACSlab
04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology
09 Interdisciplinary Units > Microscopy Imaging Center MIC

UniBE Contributor:

Berezowska, Sabina Anna; Galván Hernández, José Alberto; Langer, Rupert; Schmid, Ralph and Marti, Thomas

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0945-6317

Publisher:

Springer

Language:

English

Submitter:

Thomas Michael Marti

Date Deposited:

20 Jan 2017 15:26

Last Modified:

20 Feb 2019 15:30

Publisher DOI:

10.1007/s00428-016-2057-z

PubMed ID:

28062918

Uncontrolled Keywords:

Glycine decarboxylase; HIF-1α; Hypoxia; Immunohistochemistry; NSCC

BORIS DOI:

10.7892/boris.93816

URI:

https://boris.unibe.ch/id/eprint/93816

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