High IL-12 p35 and IL-23 p19 mRNA expression is associated with superior outcome in ovarian cancer.
OBJECTIVE
Interleukin-12 (IL-12) and IL-23 share a common p40 subunit that is either covalently linked to the p35 (IL-12) or to the p19 subunit (IL-23). Data from genetic animal models suggest that in contrast to the central role of IL-12 for tumor immune-surveillance, its close relative IL-23 rather promotes tumor growth. It was the aim of this project to evaluate the clinical significance of these findings.


METHODS
Intra-tumoral mRNA expression levels of the IL-12 specific subunit p35 and the IL-23 specific subunit p19 were quantified in ovarian cancer specimens (n=112) and control samples from healthy ovary tissue specimens (n=20) and correlated with clinical outcome.


RESULTS
Both cytokines were expressed at higher levels in ovarian cancer specimens as compared to healthy controls. p35 and p19 mRNA expression levels positively correlated in both malignant and healthy ovarian tissue. High p35 and p19 mRNA expression was associated with a significant better overall survival (OS) in the overall cohort. p35 mRNA correlated with superior outcome in advanced stage disease (FIGO III/IV), whereas the effect of high p19 mRNA expression was pre-dominant in early stage disease (FIGO I/II). Multivariate analysis revealed that p35 mRNA expression represents an independent predictor for OS but not for PFS in ovarian cancer.


CONCLUSIONS
In contrast to the recently proposed opposing roles of IL-12 and IL-23 for cancer growth and progression in rodents, our data from a large patient cohort rather suggest that high intra-tumoral expression levels of p35 mRNA and p19 mRNA are associated with a superior clinical outcome.
Wolf
Anna Maria
AM
Tyrolean Cancer Research Institute Innsbruck, Innsbruck, Austria.
Rumpold
Holger
H
Reimer
Daniel
D
Marth
Christian
C
Zeimet
Alain G
AG
Wolf
Dominik
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017252:CD3 Complex / Q000096:biosynthesis / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D053765:Interleukin-12 Subunit p35 / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D053760:Interleukin-23 Subunit p19 / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000276:immunology; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D015996:Survival Rate; D055815:Young Adult
D017252:CD3 Complex; D053765:Interleukin-12 Subunit p35; D053760:Interleukin-23 Subunit p19; D012333:RNA, Messenger