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Integrative computational immunogenomic profiling of cortisol-secreting adrenocortical carcinoma.

Publication ,  Journal Article
Baechle, JJ; Hanna, DN; Sekhar, KR; Rathmell, JC; Rathmell, WK; Baregamian, N
Published in: Journal of cellular and molecular medicine
November 2021

Adrenocortical carcinoma (ACC) is a rare but highly aggressive malignancy. Nearly half of ACC tumours overproduce and secrete adrenal steroids. Excess cortisol secretion, in particular, has been associated with poor prognosis among ACC patients. Furthermore, recent immunotherapy clinical trials have demonstrated significant immunoresistance among cortisol-secreting ACC (CS-ACC) patients when compared to their non-cortisol-secreting (nonCS-ACC) counterparts. The immunosuppressive role of excess glucocorticoid therapies and hypersecretion is known; however, the impact of the cortisol hypersecretion on ACC tumour microenvironment (TME), immune expression profiles and immune cell responses remain largely undefined. In this study, we characterized the TME of ACC patients and compared the immunogenomic profiles of nonCS-ACC and CS-ACC tumours to assess the impact of differentially expressed genes (DEGs) by utilizing The Cancer Genome Atlas (TCGA) database. Immunogenomic comparison (CS- vs. nonCS-ACC tumour TMEs) demonstrated an immunosuppressive expression profile with a direct impact on patient survival. We identified several primary prognostic indicators and potential targets within ACC tumour immune landscape. Differentially expressed immune genes with prognostic significance provide additional insight into the understanding of potential contributory mechanisms underlying failure of initial immunotherapeutic trials and poor prognosis of patients with CS-ACC.

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Published In

Journal of cellular and molecular medicine

DOI

EISSN

1582-4934

ISSN

1582-1838

Publication Date

November 2021

Volume

25

Issue

21

Start / End Page

10061 / 10072

Related Subject Headings

  • Tumor-Associated Macrophages
  • Lymphocytes, Tumor-Infiltrating
  • Hydrocortisone
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling
  • Disease Susceptibility
  • Databases, Genetic
  • Computational Biology
  • Biochemistry & Molecular Biology
 

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Baechle, J. J., Hanna, D. N., Sekhar, K. R., Rathmell, J. C., Rathmell, W. K., & Baregamian, N. (2021). Integrative computational immunogenomic profiling of cortisol-secreting adrenocortical carcinoma. Journal of Cellular and Molecular Medicine, 25(21), 10061–10072. https://doi.org/10.1111/jcmm.16936
Baechle, Jordan J., David N. Hanna, Konjeti R. Sekhar, Jeffrey C. Rathmell, W Kimryn Rathmell, and Naira Baregamian. “Integrative computational immunogenomic profiling of cortisol-secreting adrenocortical carcinoma.Journal of Cellular and Molecular Medicine 25, no. 21 (November 2021): 10061–72. https://doi.org/10.1111/jcmm.16936.
Baechle JJ, Hanna DN, Sekhar KR, Rathmell JC, Rathmell WK, Baregamian N. Integrative computational immunogenomic profiling of cortisol-secreting adrenocortical carcinoma. Journal of cellular and molecular medicine. 2021 Nov;25(21):10061–72.
Baechle, Jordan J., et al. “Integrative computational immunogenomic profiling of cortisol-secreting adrenocortical carcinoma.Journal of Cellular and Molecular Medicine, vol. 25, no. 21, Nov. 2021, pp. 10061–72. Epmc, doi:10.1111/jcmm.16936.
Baechle JJ, Hanna DN, Sekhar KR, Rathmell JC, Rathmell WK, Baregamian N. Integrative computational immunogenomic profiling of cortisol-secreting adrenocortical carcinoma. Journal of cellular and molecular medicine. 2021 Nov;25(21):10061–10072.
Journal cover image

Published In

Journal of cellular and molecular medicine

DOI

EISSN

1582-4934

ISSN

1582-1838

Publication Date

November 2021

Volume

25

Issue

21

Start / End Page

10061 / 10072

Related Subject Headings

  • Tumor-Associated Macrophages
  • Lymphocytes, Tumor-Infiltrating
  • Hydrocortisone
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling
  • Disease Susceptibility
  • Databases, Genetic
  • Computational Biology
  • Biochemistry & Molecular Biology