MSI2 expression in adrenocortical carcinoma: Association with unfavorable prognosis and correlation with steroid and immune‐related pathways

Abstract

Adrenocortical carcinoma (ACC) is a rare, but highly aggressive cancer of the adrenal cortex with a generally poor prognosis. Despite being rare, completely resected ACCs present a high risk of recurrence. Musashi‐2 (MSI2) has recently been recognized as a potential prognostic biomarker and therapeutic target in many cancers. However, no studies have evaluated the clinical significance of MSI2 expression in ACC. Here, we addressed MSI2 expression and its association with ACC prognosis and clinicopathological parameters. MSI2 expression was analyzed in TCGA, GSE12368, GSE33371, and GSE49278 ACC datasets; and its correlation with other genes and immune cell infiltration were investigated by using the R2: Genomics Analysis and Visualization Platform and TIMER databases, respectively. Enrichment analysis was performed with the DAVID Functional Annotation Tool. Kaplan–Meier curves, log‐rank tests, and Cox regression analyses were used to explore the prognostic role of MSI2 in ACC. Our findings demonstrated the potential value of MSI2 overexpression as an independent predictor of poor prognosis in patients with completely resected ACC (hazard ratio 6.715, 95% confidence interval 1.266 – 35.620, p =.025). In addition, MSI2 overexpression was associated with characteristics of unfavorable prognosis, such as cortisol excess (p = .002), recurrence (p =.003), and death (p =.015); positively correlated with genes related to steroid biosynthesis (p < .05); and negatively correlated with immune‐related pathways (p < .05). Our findings demonstrate that MSI2 has value as a prognostic marker for completely resected ACC and reinforce the investigation of its role as a possible therapeutic target for patients with ACC.

Prognostic value of Musashi 2 (MSI2) in cancer patients: A systematic review and meta-analysis

“…MSI2 has been proved to be significantly up-regulated in various cancers, such as ovarian carcinoma (OC) ( 19 ), non-small cell lung cancer (NSCLC) ( 20 ), colorectal cancer (CRC) ( 21 ), cervical cancer (CC) ( 16 ), et al. Moreover, excessive MSI2 expression is associated with poor prognosis in numerous solid tumors as well as in hematological malignancies ( 9 , 15 , 19 – 39 ), but the results are controversial ( 16 , 32 , 35 , 36 , 40 , 41 ). Hence, we carried out this meta-analysis to further analyze the prognostic value of MSI2, so as to provide a theoretical basis for the prognosis and treatment of patients with cancer.…”