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Title:Gene expression levels of the prolyl hydroxylase domain proteins PHD1 and PHD2 but not PHD3 are decreased in primary tumours and correlate with poor prognosis of patients with surgically resected non-small-cell lung cancer
Authors:Koren, Ana (Author)
Rijavec, Matija (Author)
Krumpestar, Tomaž (Author)
Kern, Izidor (Author)
Sadikov, Aleksander (Author)
Čufer, Tanja (Author)
Korošec, Peter (Author)
Language:English
Tipology:1.01 - Original Scientific Article
Organisation:Logo UKPBAG - University Clinic of Respiratory and Allergic Diseases Golnik
Abstract:Background: Hypoxia correlates with poor prognosis in several cancer types, including lung cancer. Prolyl hydroxylase domain proteins (PHDs) play a role in cell oxygen sensing, negatively regulating the hypoxia-inducible factor (HIF) pathway. Our study aim was to evaluate PHD1, PHD2 and PHD3 mRNA expression levels in primary tumours and normal lungs of non-small-cell lung cancer (NSCLC) patients and to correlate it with selected regulators of HIF signalling, with clinicopathological characteristics and overall survival (OS). Methods: Tumour tissue samples were obtained from 60 patients with surgically resected NSCLC who were treated with radical surgery. In 22 out of 60 cases, matching morphologically normal lung tissue was obtained. PHD1, PHD2 and PHD3 mRNA expressions were measured using RT-qPCR. Results: The PHD1 and PHD2 mRNA levels in primary tumours were significantly decreased compared to those in normal lungs (both p < 0.0001). PHD1 and PHD2 expression in tumours was positively correlated (rs = 0.82; p < 0.0001) and correlated well with HIF pathway downstream genes HIF1A, PKM2 and PDK1. Decreased PHD1 and PHD2 were associated with larger tumour size, higher tumour stage (PHD1 only) and squamous cell carcinoma. Patients with low PHD1 and patients with low PHD2 expression had shorter OS than patients with high PHD1 (p = 0.02) and PHD2 expression (p = 0.01). PHD1 showed borderline independent prognostic values in multivariate analysis (p = 0.06). In contrast, we found no associations between PHD3 expression and any of the observed parameters. Conclusions: Our results show that reduced expression of PHD1 and PHD2 is associated with the development and progression of NSCLC. PHD1 could be further assessed as a prognostic marker in NSCLC.
Keywords:non-small-cell lung carcinoma, prognosis, non-small cell lung cancer, mRNA expression, prolyl hydroxylase domain proteins
Year of publishing:2021
Publisher:MDPI
Source:Švica
COBISS_ID:63269891 Link is opened in a new window
UDC:616-006
ISSN on article:2072-6694
DOI:10.3390/cancers13102309 Link is opened in a new window
Note:Nasl. z nasl. zaslona; Soavtorji: Matija Rijavec, Tomaž Krumpestar, Izidor Kern, Aleksander Sadikov, Tanja Čufer, Peter Korošec; Opis vira z dne 14. 5. 2021; Št. prispevka: 2309;
Views:456
Downloads:296
Files:.pdf PDF - Presentation file, download (820,49 KB)
URL URL - Source URL, visit https://www.mdpi.com/2072-6694/13/10/2309/pdf
 
Journal:Cancers
MDPI
 
Metadata:XML RDF-CHPDL DC-XML DC-RDF
Rights:© 2021 by the authors
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License:CC BY 4.0, Creative Commons Attribution 4.0 International
Link:http://creativecommons.org/licenses/by/4.0/
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Licensing start date:12.05.2021

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