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 in | PloS one Vol. 16; no. 2; p. e0246632 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
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Public Library of Science
01.02.2021
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ISSN | 1932-6203 1932-6203 |
DOI | 10.1371/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 |
AuthorAffiliation_xml | – name: 2 Department of Zoology, Chaudhary Charan Singh University, Meerut, Uttar Pradesh, India – name: University of Nebraska Medical Center, UNITED STATES – name: 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 |
Author_xml | – sequence: 1 givenname: Abhinav orcidid: 0000-0003-3457-0215 surname: Kumar fullname: Kumar, Abhinav – sequence: 2 givenname: Ian H. surname: Bellayr fullname: Bellayr, Ian H. – sequence: 3 givenname: Hridaya S. surname: Singh fullname: Singh, Hridaya S. – sequence: 4 givenname: Raj K. orcidid: 0000-0003-2548-346X surname: Puri fullname: Puri, Raj K. |
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CitedBy_id | crossref_primary_10_3390_ijms25073780 crossref_primary_10_3390_ph17111526 crossref_primary_10_3389_fimmu_2022_878365 |
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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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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 |
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