Construction of a risk signature for adrenocortical carcinoma using immune-related genes

Abstract

Background: Adrenocortical carcinoma (ACC) is considered a rare tumor with a dismal prognosis. Expression of immune-related genes (IRGs) in ACC and correlations between IRGs and ACC prognosis were assessed using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases.Methods: To preliminarily predict immune cell infiltration, an immune score was calculated using ESTIMATE. Differentially expressed IRGs were screened, and potential biological functions were investigated. We then performed univariate Cox regression to identify IRGs associated with survival, and the regulatory mechanisms of IRGs associated with survival were predicted. We built a risk signature through multivariate Cox regression to evaluate patient overall survival (OS).Results: A high immune score predicted a good prognosis and an early clinical stage in ACC. We identified 30 IRGs associated with survival and then predicted associated regulatory mechanisms via protein-protein interaction (PPI) and transcription factor (TF) regulatory networks. The risk signature established by multivariate Cox regression correlated significantly with prognosis in ACC. Conclusions:The vital roles of IRGs in ACC were assessed, and the risk signature obtained based on IRGs associated with survival independently predicted ACC prognosis.

The Role of Biomarkers in Adrenocortical Carcinoma: A Review of Current Evidence and Future Perspectives

“…It is possible that higher pro-inflammatory cytokine concentrations comprise an additional cardiovascular, metabolic and perhaps malignancy risk in these patients [ 128 ]. High IL-6 high level might stimulate the secretion of glucocorticoids and the serum level of matrix metallopeptidase 9, which is related to the cancer pathology including invasion, metastasis and angiogenesis [ 129 ]. Matrix metalloproteinase (MMP), are calcium-dependent zinc-containing endopeptidase playing an important role in tissue remodeling associated with various physiological or pathological processes including metastasis.…”

“…To predict immune cell infiltration, an immune score was calculated using ESTIMATE (Estimation of Stromal and Immune cells in Malignant Tumor tissues with Expression data). A high immune score predicted a good prognosis and an early clinical stage in ACC [ 129 ]. Results have shown that the five most significant signaling pathways for activation of the differentially expressed IRGs were the PI3K–Akt, JAK–STAT, chemokine signaling pathways, and the Ras and MAPK signaling pathway [ 129 ].…”

“…A high immune score predicted a good prognosis and an early clinical stage in ACC [ 129 ]. Results have shown that the five most significant signaling pathways for activation of the differentially expressed IRGs were the PI3K–Akt, JAK–STAT, chemokine signaling pathways, and the Ras and MAPK signaling pathway [ 129 ]. Analysis has identified 30 IRGs associated with survival [ 129 ].…”

“…Results have shown that the five most significant signaling pathways for activation of the differentially expressed IRGs were the PI3K–Akt, JAK–STAT, chemokine signaling pathways, and the Ras and MAPK signaling pathway [ 129 ]. Analysis has identified 30 IRGs associated with survival [ 129 ]. Among all of them, centromere protein A (CENPA), E2F transcription factor 1 (E2F1) and forkhead box M1 (FOMX1) have shown upregulated expression that was involved in ACC progression and were predictors of worse outcome.…”

“…Among all of them, centromere protein A (CENPA), E2F transcription factor 1 (E2F1) and forkhead box M1 (FOMX1) have shown upregulated expression that was involved in ACC progression and were predictors of worse outcome. In contrast, downregulation of transcription factor 21 (TCF21) expression resulted in the accumulation of secreted glucocorticoids and accelerated proliferation of ACC cells [ 129 ].…”