A Hypoxia Signature for Predicting Prognosis and Tumor Immune Microenvironment in Adrenocortical Carcinoma

Abstract

Adrenocortical carcinoma (ACC) is a rare malignancy with dismal prognosis. Hypoxia is one of characteristics of cancer leading to tumor progression. For ACC, however, no reliable prognostic signature on the basis of hypoxia genes has been built. Our study aimed to develop a hypoxia-associated gene signature in ACC. Data of ACC patients were obtained from TCGA and GEO databases. The genes included in hypoxia risk signature were identified using the Cox regression analysis as well as LASSO regression analysis. GSEA was applied to discover the enriched gene sets. To detect a possible connection between the gene signature and immune cells, the CIBERSORT technique was applied. In ACC, the hypoxia signature including three genes (CCNA2, COL5A1, and EFNA3) was built to predict prognosis and reflect the immune microenvironment. Patients with high-risk scores tended to have a poor prognosis. According to the multivariate regression analysis, the hypoxia signature could be served as an independent indicator in ACC patients. GSEA demonstrated that gene sets linked to cancer proliferation and cell cycle were differentially enriched in high-risk classes. Additionally, we found that PDL1 and CTLA4 expression were significantly lower in the high-risk group than in the low-risk group, and resting NK cells displayed a significant increase in the high-risk group. In summary, the hypoxia risk signature created in our study might predict prognosis and evaluate the tumor immune microenvironment for ACC.

CCNA2 as an Immunological Biomarker Encompassing Tumor Microenvironment and Therapeutic Response in Multiple Cancer Types

“…Zhou et al found that CCNA2 is a potential diagnostic and prognostic biomarker for LUAD, and CCNA2 expression positively correlated with immunity therapy efficiency in LUAD [42]. Chen et al also confirmed that CCNA2 is involved in hypoxia signature affecting the clinical outcomes and immune microenvironment of ACC [43]. To date, only several studies assessed the immune role of CCNA2 in cancers.…”

Modulation of Autophagy in Adrenal Tumors

“…Indeed, autophagy might act as a survival mechanism for tumor hypoxic cells through recycling of cellular constituents. The hypoxia risk signature was recently suggested to be able to predict prognosis and evaluate the tumor immune microenvironment of ACC (82) and also the long common history between hypoxia and PCC (83), indicate to us that in adrenal tumorsit would be interesting to study the hypoxia status and relate it with improved therapeutic strategies using autophagy modulation.…”

Hypoxia signaling pathway: A central mediator in endocrine tumors

“…Tumor associated hypoxia could be one of the players of erythropoietin production in tumor cells. Recently, a bioinformatic study has reported that a hypoxia-related gene signature could predict prognosis and reflect the immune microenvironment in ACC ( 126 ). Specifically, based on hypoxia-related gene expression, ACC patients in the TCGA database were divided into three molecular subtypes (C1, C2, and C3), each with different clinical outcomes with C3 having reported of shortest survival ( 127 ).…”