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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
ID
Koren, Ana
(
Avtor
),
ID
Rijavec, Matija
(
Avtor
),
ID
Krumpestar, Tomaž
(
Avtor
),
ID
Kern, Izidor
(
Avtor
),
ID
Sadikov, Aleksander
(
Avtor
),
ID
Čufer, Tanja
(
Avtor
),
ID
Korošec, Peter
(
Avtor
)
PDF - Predstavitvena datoteka,
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MD5: C5CC7167711499EAC9EB7DF77EF5586E
URL - Izvorni URL, za dostop obiščite
https://www.mdpi.com/2072-6694/13/10/2309
Galerija slik
Izvleček
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 (r$_s$ = 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.
Jezik:
Angleški jezik
Ključne besede:
non-small-cell lung cancer
,
mRNA expression
,
prolyl hydroxylase domain proteins
,
carcinoma
,
prognosis
Vrsta gradiva:
Članek v reviji
Tipologija:
1.01 - Izvirni znanstveni članek
Organizacija:
FRI - Fakulteta za računalništvo in informatiko
MF - Medicinska fakulteta
Status publikacije:
Objavljeno
Različica publikacije:
Objavljena publikacija
Leto izida:
2021
Št. strani:
14 str.
Številčenje:
Vol. 13, iss. 10, art. 2309
PID:
20.500.12556/RUL-135654
UDK:
616-006
ISSN pri članku:
2072-6694
DOI:
10.3390/cancers13102309
COBISS.SI-ID:
63269891
Datum objave v RUL:
23.03.2022
Število ogledov:
1185
Število prenosov:
104
Metapodatki:
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Objavi na:
Gradivo je del revije
Naslov:
Cancers
Skrajšan naslov:
Cancers
Založnik:
MDPI
ISSN:
2072-6694
COBISS.SI-ID:
517914137
Licence
Licenca:
CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:
http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:
To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
Začetek licenciranja:
12.05.2021
Sekundarni jezik
Jezik:
Slovenski jezik
Ključne besede:
izražanje mRNA
,
beljakovine s prolil hidroksilazno domeno
,
nedrobnocelični karcinom pljuč
,
prognoza
Projekti
Financer:
ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:
J3-7372
Naslov:
Molekularni označevalci raka pljuč in njim prilagojeno zdravljenje
Financer:
ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:
P3-0360
Naslov:
Celostna obravnava alergijskih bolezni in astme v Sloveniji: od epidemiologije do genetike
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