Abstract
BackgroundAdrenocortical carcinoma (ACC) is an aggressive and rare malignant tumor and is prone to local invasion and metastasis. And, overexpressed Centromere Protein F (CENPF) is closely related to the oncogenesis of various neoplasms, including ACC. However, the prognosis and exact biological function of CENPF in ACC remains largely unclear.MethodsIn the present essay, the expression patterns and prognostic value of CENPF in ACC were investigated in clinical specimens and public cancer databases, including GEO and TCGA. The potential signaling mechanism of CENPF in ACC was studied based on gene-set enrichment analysis (GSEA). Furthermore, a small RNA interference experiment was conducted to probe the underlying biological function of CENPF in the human ACC cell line, SW13 cells. Lastly, two available therapeutic strategies, including immunotherapy and chemotherapy, have been further explored.ResultsThe expression of CENPF in human ACC samples, GEO, and TCGA databases depicted that CENPF was overtly hyper-expressed in ACC patients and positively correlated with tumor stage. The aberrant expression of CENPF was significantly correlated with unfavorable overall survival (OS) in ACC patients. Then, the GSEA analysis declared that CENPF was mainly involved in the G2/M-phase mediated cell cycle and p53 signaling pathway. Further, the in vitro experiment demonstrated that the interaction between CENPF and CDK1 augmented the G2/M-phase transition of mitosis, cell proliferation and might induce p53 mediated anti-tumor effect in human ACC cell line, SW13 cells. Lastly, immune infiltration analysis highlighted that ACC patients with high CENPF expression harbored significantly different immune cell populations, and high TMB/MSI score. The gene-drug interaction network stated that CENPF inhibitors, such as Cisplatin, Sunitinib, and Etoposide, might serve as potential drugs for the therapy of ACC.ConclusionThe result points out that CENPF is significantly overexpressed in ACC patients. The overexpressed CENPF predicts a poor prognosis of ACC and might augment the progress of ACC. Thus, CENPF and related genes might serve as a novel prognostic biomarker or latent therapeutic target for ACC patients.
Highlights
Adrenocortical carcinoma (ACC) is an aggressive and rare malignant tumor and is prone to local inva‐ sion and metastasis
Adrenocortical carcinoma (ACC), as an invasive and rare malignant neoplasm that originated from the adrenal cortex, is prone to local invasion and metastasis through blood and lymph nodes, accounting for 14% of primary adrenal incidentalomas [1]
Accumulative literatures have demonstrated that inhibition of WNT–β-catenin signaling pathway [10], cell-cycle progression through down-regulation of p53–RB [11], defects in mismatch repair related enzymes [12], DNA methylation [13], and abnormal maintenance of telomere (ATRX [14, 15], DAX [16] and TERT [8, 17]), were closely bound up with the deterioration and poor prognosis of ACC
Summary
The expression patterns and prognostic value of CENPF in ACC were investigated in clinical specimens and public cancer databases, including GEO and TCGA. Clinical specimens All Formalin-fixed and paraffin-embedded (PPFE) samples were collected from patients diagnosed as ACC and adrenocortical adenoma and stored at 20–25 °C, from Jan 2011 to Jan 2021 at Taihe Hospital of Hubei University of Medicine, China. 6 cases of ACC, 12 cases of adrenocortical adenoma (benign tumor), and 12 cases of normal adrenal cortex samples (adjacent to adrenocortical adenoma) were involved in this study. Histological analysis Hematoxylin–eosin (HE) and immunohistochemistry (IHC) staining of PPFE samples were conducted following the steps in the manufacturer’s instructions. 3 μm of ACC tissues, adrenocortical adenoma tissues, and normal adrenal cortex tissues were sliced from the PPFE. The 3% hydrogen peroxide was used to block endogenous peroxidase activity in methanol for
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