IL-13Rα2 gene expression is a biomarker of adverse outcome in patients with adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine malignancy that usually results in a fatal outcome. To allow the better clinical management and reduce mortality, we searched for clinical and molecular markers that are reliable predictor of disease severity and clinical outcome in A...

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Published inPloS one Vol. 16; no. 2; p. e0246632
Main Authors Kumar, Abhinav, Bellayr, Ian H., Singh, Hridaya S., Puri, Raj K.
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 01.02.2021
Public Library of Science (PLoS)
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ISSN1932-6203
1932-6203
DOI10.1371/journal.pone.0246632

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Abstract Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine malignancy that usually results in a fatal outcome. To allow the better clinical management and reduce mortality, we searched for clinical and molecular markers that are reliable predictor of disease severity and clinical outcome in ACC patients. We determined a correlation between the overexpression of IL-13R α2 and the clinical outcome in ACC patients using comprehensive data available in The Cancer Genome Atlas (TCGA) database. The dataset of 79 ACC subjects were divided into groups of low, medium, or high expression of IL-13R α2 as determined by RNA-seq. These patients were also stratified by length of survival, overall survival, incidence of a new tumor event, incidence of metastasis, and production of excess hormones. We report a correlation between IL-13R α2 expression and survival of subjects with ACC. High expression of IL-13Rα 2 in ACC tumors was significantly associated with a lower patient survival rate and period of survival compared to low expression (p = 0.0084). In addition, high IL-13R α2 expression was significantly associated with a higher incidence of new tumor events and excess hormone production compared to low or medium IL-13R α2 expression. Within the cohort of patients that produced excess hormone, elevated IL-13R α2 expression was significantly associated with a lower survival rate. Additionally, IL-13R α1 had a potential relationship between transcript level and ACC survival. Our results and promising antitumor activity in preclinical models and trials indicate that IL-13R α2 expression is an important prognostic biomarker of ACC disease outcome and a promising target for therapeutic treatment of ACC.
AbstractList Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine malignancy that usually results in a fatal outcome. To allow the better clinical management and reduce mortality, we searched for clinical and molecular markers that are reliable predictor of disease severity and clinical outcome in ACC patients. We determined a correlation between the overexpression of IL-13Rα2 and the clinical outcome in ACC patients using comprehensive data available in The Cancer Genome Atlas (TCGA) database. The dataset of 79 ACC subjects were divided into groups of low, medium, or high expression of IL-13Rα2 as determined by RNA-seq. These patients were also stratified by length of survival, overall survival, incidence of a new tumor event, incidence of metastasis, and production of excess hormones. We report a correlation between IL-13Rα2 expression and survival of subjects with ACC. High expression of IL-13Rα2 in ACC tumors was significantly associated with a lower patient survival rate and period of survival compared to low expression (p = 0.0084). In addition, high IL-13Rα2 expression was significantly associated with a higher incidence of new tumor events and excess hormone production compared to low or medium IL-13Rα2 expression. Within the cohort of patients that produced excess hormone, elevated IL-13Rα2 expression was significantly associated with a lower survival rate. Additionally, IL-13Rα1 had a potential relationship between transcript level and ACC survival. Our results and promising antitumor activity in preclinical models and trials indicate that IL-13Rα2 expression is an important prognostic biomarker of ACC disease outcome and a promising target for therapeutic treatment of ACC.Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine malignancy that usually results in a fatal outcome. To allow the better clinical management and reduce mortality, we searched for clinical and molecular markers that are reliable predictor of disease severity and clinical outcome in ACC patients. We determined a correlation between the overexpression of IL-13Rα2 and the clinical outcome in ACC patients using comprehensive data available in The Cancer Genome Atlas (TCGA) database. The dataset of 79 ACC subjects were divided into groups of low, medium, or high expression of IL-13Rα2 as determined by RNA-seq. These patients were also stratified by length of survival, overall survival, incidence of a new tumor event, incidence of metastasis, and production of excess hormones. We report a correlation between IL-13Rα2 expression and survival of subjects with ACC. High expression of IL-13Rα2 in ACC tumors was significantly associated with a lower patient survival rate and period of survival compared to low expression (p = 0.0084). In addition, high IL-13Rα2 expression was significantly associated with a higher incidence of new tumor events and excess hormone production compared to low or medium IL-13Rα2 expression. Within the cohort of patients that produced excess hormone, elevated IL-13Rα2 expression was significantly associated with a lower survival rate. Additionally, IL-13Rα1 had a potential relationship between transcript level and ACC survival. Our results and promising antitumor activity in preclinical models and trials indicate that IL-13Rα2 expression is an important prognostic biomarker of ACC disease outcome and a promising target for therapeutic treatment of ACC.
About the Authors: Abhinav Kumar Roles Conceptualization, Data curation, Formal analysis, Writing – original draft, Writing – review & editing Affiliation: Division of Cellular and Gene Therapies, Tumor Vaccines and Biotechnology Branch, Center for Biologics and Evaluation Research, US Food and Drug Administration, Silver Spring, Maryland, United States of America ORCID logo https://orcid.org/0000-0003-3457-0215 Ian H. Bellayr Roles Conceptualization, Supervision, Writing – review & editing Current address: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America Affiliation: Division of Cellular and Gene Therapies, Tumor Vaccines and Biotechnology Branch, Center for Biologics and Evaluation Research, US Food and Drug Administration, Silver Spring, Maryland, United States of America Hridaya S. Singh Roles Supervision, Writing – review & editing Affiliation: Department of Zoology, Chaudhary Charan Singh University, Meerut, Uttar Pradesh, India Raj K. Puri Roles Conceptualization, Resources, Supervision, Writing – review & editing * E-mail: Raj.Puri@fda.hhs.gov Affiliation: Division of Cellular and Gene Therapies, Tumor Vaccines and Biotechnology Branch, Center for Biologics and Evaluation Research, US Food and Drug Administration, Silver Spring, Maryland, United States of America ORCID logo https://orcid.org/0000-0003-2548-346X Introduction Adrenocortical carcinoma (ACC) is a highly aggressive malignancy that originates in the outer layer of the adrenal gland. In these cases, the risk of mortality is high as the tumor has grown significantly and metastasized. [...]early detection is needed to reduce the high mortality rate from ACC. Because IL-13Rα2 binds IL-13 with higher affinity than IL-13Rα1 [13, 14], it thereby allows sequestration of the ligand away from IL-13Rα1 for IL-13 signaling.
About the Authors: Abhinav Kumar Roles Conceptualization, Data curation, Formal analysis, Writing – original draft, Writing – review & editing Affiliation: Division of Cellular and Gene Therapies, Tumor Vaccines and Biotechnology Branch, Center for Biologics and Evaluation Research, US Food and Drug Administration, Silver Spring, Maryland, United States of America ORCID logo https://orcid.org/0000-0003-3457-0215 Ian H. Bellayr Roles Conceptualization, Supervision, Writing – review & editing Current address: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America Affiliation: Division of Cellular and Gene Therapies, Tumor Vaccines and Biotechnology Branch, Center for Biologics and Evaluation Research, US Food and Drug Administration, Silver Spring, Maryland, United States of America Hridaya S. Singh Roles Supervision, Writing – review & editing Affiliation: Department of Zoology, Chaudhary Charan Singh University, Meerut, Uttar Pradesh, India Raj K. Puri Roles Conceptualization, Resources, Supervision, Writing – review & editing * E-mail: Raj.Puri@fda.hhs.gov Affiliation: Division of Cellular and Gene Therapies, Tumor Vaccines and Biotechnology Branch, Center for Biologics and Evaluation Research, US Food and Drug Administration, Silver Spring, Maryland, United States of America ORCID logo https://orcid.org/0000-0003-2548-346X Introduction Adrenocortical carcinoma (ACC) is a highly aggressive malignancy that originates in the outer layer of the adrenal gland. In these cases, the risk of mortality is high as the tumor has grown significantly and metastasized. [...]early detection is needed to reduce the high mortality rate from ACC. Because IL-13Rα2 binds IL-13 with higher affinity than IL-13Rα1 [13, 14], it thereby allows sequestration of the ligand away from IL-13Rα1 for IL-13 signaling.
Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine malignancy that usually results in a fatal outcome. To allow the better clinical management and reduce mortality, we searched for clinical and molecular markers that are reliable predictor of disease severity and clinical outcome in ACC patients. We determined a correlation between the overexpression of IL-13Rα2 and the clinical outcome in ACC patients using comprehensive data available in The Cancer Genome Atlas (TCGA) database. The dataset of 79 ACC subjects were divided into groups of low, medium, or high expression of IL-13Rα2 as determined by RNA-seq. These patients were also stratified by length of survival, overall survival, incidence of a new tumor event, incidence of metastasis, and production of excess hormones. We report a correlation between IL-13Rα2 expression and survival of subjects with ACC. High expression of IL-13Rα2 in ACC tumors was significantly associated with a lower patient survival rate and period of survival compared to low expression (p = 0.0084). In addition, high IL-13Rα2 expression was significantly associated with a higher incidence of new tumor events and excess hormone production compared to low or medium IL-13Rα2 expression. Within the cohort of patients that produced excess hormone, elevated IL-13Rα2 expression was significantly associated with a lower survival rate. Additionally, IL-13Rα1 had a potential relationship between transcript level and ACC survival. Our results and promising antitumor activity in preclinical models and trials indicate that IL-13Rα2 expression is an important prognostic biomarker of ACC disease outcome and a promising target for therapeutic treatment of ACC.
Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine malignancy that usually results in a fatal outcome. To allow the better clinical management and reduce mortality, we searched for clinical and molecular markers that are reliable predictor of disease severity and clinical outcome in ACC patients. We determined a correlation between the overexpression of IL-13R α2 and the clinical outcome in ACC patients using comprehensive data available in The Cancer Genome Atlas (TCGA) database. The dataset of 79 ACC subjects were divided into groups of low, medium, or high expression of IL-13R α2 as determined by RNA-seq. These patients were also stratified by length of survival, overall survival, incidence of a new tumor event, incidence of metastasis, and production of excess hormones. We report a correlation between IL-13R α2 expression and survival of subjects with ACC. High expression of IL-13Rα 2 in ACC tumors was significantly associated with a lower patient survival rate and period of survival compared to low expression (p = 0.0084). In addition, high IL-13R α2 expression was significantly associated with a higher incidence of new tumor events and excess hormone production compared to low or medium IL-13R α2 expression. Within the cohort of patients that produced excess hormone, elevated IL-13R α2 expression was significantly associated with a lower survival rate. Additionally, IL-13R α1 had a potential relationship between transcript level and ACC survival. Our results and promising antitumor activity in preclinical models and trials indicate that IL-13R α2 expression is an important prognostic biomarker of ACC disease outcome and a promising target for therapeutic treatment of ACC.
Author Bellayr, Ian H.
Kumar, Abhinav
Puri, Raj K.
Singh, Hridaya S.
AuthorAffiliation University of Nebraska Medical Center, UNITED STATES
1 Division of Cellular and Gene Therapies, Tumor Vaccines and Biotechnology Branch, Center for Biologics and Evaluation Research, US Food and Drug Administration, Silver Spring, Maryland, United States of America
2 Department of Zoology, Chaudhary Charan Singh University, Meerut, Uttar Pradesh, India
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/33591997$$D View this record in MEDLINE/PubMed
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CitedBy_id crossref_primary_10_3390_ijms25073780
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Competing Interests: The authors have declared that no competing interests exist.
Current address: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
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Snippet Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine malignancy that usually results in a fatal outcome. To allow the better clinical management...
About the Authors: Abhinav Kumar Roles Conceptualization, Data curation, Formal analysis, Writing – original draft, Writing – review & editing Affiliation:...
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StartPage e0246632
SubjectTerms Adrenal glands
Age
Allergies
Apoptosis
Biological products
Biology and Life Sciences
Biomarkers
Biotechnology
Cancer vaccines
Cell division
Datasets
Disease
Editing
Gene expression
Gene therapy
Genomes
Genomics
Head & neck cancer
Hypersensitivity
Infectious diseases
Interleukin 13
Kidney cancer
Ligands
Malignancy
Medical prognosis
Medicine and Health Sciences
Metastasis
Mortality
Mortality risk
Mutation
Neuroendocrine tumors
Patients
Signal transduction
Survival analysis
Tumors
Vaccines
Zoology
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Title IL-13Rα2 gene expression is a biomarker of adverse outcome in patients with adrenocortical carcinoma
URI https://www.ncbi.nlm.nih.gov/pubmed/33591997
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https://doaj.org/article/d00da1c5afee48bd9e003ae5a7f1f57e
http://dx.doi.org/10.1371/journal.pone.0246632
Volume 16
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