Serum IL6 as a Prognostic Biomarker and IL6R as a Therapeutic Target in Biliary Tract Cancers.
Adult
Aged
Aged, 80 and over
Animals
Antigens, Tumor-Associated, Carbohydrate
/ blood
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Biliary Tract Neoplasms
/ blood
Biomarkers, Tumor
/ blood
Cell Proliferation
/ drug effects
Chitinase-3-Like Protein 1
/ blood
Deoxycytidine
/ administration & dosage
Disease-Free Survival
Female
Humans
Interleukin-6
/ blood
Male
Mice
Middle Aged
Palliative Care
Prognosis
Progression-Free Survival
Receptors, Interleukin-6
/ antagonists & inhibitors
Gemcitabine
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 11 2020
01 11 2020
Historique:
received:
16
08
2019
revised:
23
04
2020
accepted:
17
08
2020
pubmed:
17
9
2020
medline:
27
11
2021
entrez:
16
9
2020
Statut:
ppublish
Résumé
Biliary tract cancer (BTC) is a heterogeneous group of rare gastrointestinal malignancies with dismal prognosis often associated with inflammation. We assessed the prognostic value of IL6 and YKL-40 compared with CA19-9 before and during palliative chemotherapy. We also investigated in mice whether IL6R inhibition in combination with gemcitabine could prolong chemosensitivity. A total of 452 Danish participants with advanced (locally advanced and metastatic) BTC were included from six clinical trials (February 2004 to March 2017). Serum CA19-9, IL6, and YKL-40 were measured before and during palliative treatment. Associations between candidate biomarkers and progression-free survival (PFS) and overall survival (OS) were analyzed by univariate and multivariate Cox regression. Effects of inhibiting IL6R and YKL-40 were assessed High pretreatment levels of CA19-9, IL6, and YKL-40, and increasing levels during treatment, were associated with short PFS and OS in patients with advanced BTC. IL6 provided independent prognostic information, independent of tumor location and in patients with normal serum CA19-9. ROC analyses showed that IL6 and YKL-40 were predictive of very short OS (OS < 6 months), whereas CA19-9 was best to predict OS > 1.5 years. Treatment with anti-IL6R and gemcitabine significantly diminished tumor growth when compared with gemcitabine monotherapy in an Serum IL6 and YKL-40 are potential new prognostic biomarkers in BTC. IL6 provides independent prognostic information and may be superior to CA19-9 in certain contexts. Moreover, anti-IL6R should be considered as a new treatment option to sustain gemcitabine response in patients with BTC.
Identifiants
pubmed: 32933994
pii: 1078-0432.CCR-19-2700
doi: 10.1158/1078-0432.CCR-19-2700
pmc: PMC8998158
mid: NIHMS1789287
doi:
Substances chimiques
Antigens, Tumor-Associated, Carbohydrate
0
Biomarkers, Tumor
0
CHI3L1 protein, human
0
Chitinase-3-Like Protein 1
0
IL6R protein, human
0
Interleukin-6
0
Receptors, Interleukin-6
0
carbohydrate antigen 199, human
0
Deoxycytidine
0W860991D6
Gemcitabine
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5655-5667Subventions
Organisme : Intramural NIH HHS
ID : ZIA BC010313
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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