title: The relationship between blood IL-12p40 level and melanoma progression.
abstract: Cytokines such as Interleukin (IL)-12p70 ("IL-12") and IL-23 can influence tumor progression. We tested the hypothesis that blood levels of IL-12p40, the common subunit of both cytokines, are associated with melanoma progression. Blood from 2,048 white melanoma patients were collected at a single institution between March 1998 and March 2011. Plasma levels of IL-12p40 were determined for 573 patients (discovery), 249 patients (Validation 1) and 244 patients (Validation 2). Per 10-unit change of IL-12p40 level was used to investigate associations with melanoma patient outcome among all patients or among patients with early or advanced stage. Among stage I/II melanoma patients in the pooled data set, after adjustment for sex, age, stage and blood draw time from diagnosis, elevated IL-12p40 was associated with melanoma recurrence [hazard ratio (HR) = 1.04 per 10-unit increase in IL-12p40, 95% CI 1.02-1.06, p = 8.48 × 10(-5) ]; Elevated IL-12p40 was also associated with a poorer melanoma specific survival (HR = 1.06, 95% CI 1.03-1.09, p = 3.35 × 10(-5) ) and overall survival (HR = 1.05, 95% CI 1.03-1.08, p = 8.78×10(-7) ) in multivariate analysis. Among stage III/IV melanoma patients in the pooled data set, no significant association was detected between elevated IL-12p40 and overall survival, or with melanoma specific survival, with or without adjustment for the above covariates. Early stage melanoma patients with elevated IL-12p40 levels are more likely to develop disease recurrence and have a poorer survival. Further investigation with a larger sample size will be needed to determine the role of IL-12p40 in advanced stage melanoma patients.
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030.
authors.forename: Shenying
authors.initials: S
authors.lastname: Fang
authors.forename: Yuling
authors.initials: Y
authors.lastname: Wang
authors.forename: Yun Shin
authors.initials: YS
authors.lastname: Chun
authors.forename: Huey
authors.initials: H
authors.lastname: Liu
authors.forename: Merrick I
authors.initials: MI
authors.lastname: Ross
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Gershenwald
authors.forename: Janice N
authors.initials: JN
authors.lastname: Cormier
authors.forename: Richard E
authors.initials: RE
authors.lastname: Royal
authors.forename: Anthony
authors.initials: A
authors.lastname: Lucci
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Schacherer
authors.forename: John D
authors.initials: JD
authors.lastname: Reveille
authors.forename: Dawen
authors.initials: D
authors.lastname: Sui
authors.forename: Roland L
authors.initials: RL
authors.lastname: Bassett
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lee
mesh_terms: D018450:Disease Progression; D005260:Female; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000097:blood*; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000473:pathology*; D008875:Middle Aged; D015999:Multivariate Analysis; D012878:Skin Neoplasms; D000096142:Cutaneous Malignant Melanoma
chemical_list: D053762:Interleukin-12 Subunit p40
keywords: IL-12p40; cytokines; early stage; melanoma; progression