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Background: Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignant tumor. Currently, there is a lack of reliable prognostic markers in clinical practice. Extensive research has shown that long non-coding RNA (lncRNA) are critical factors in the initiation and progression of cancer, closely associated with early diagnosis and prognosis. Previous studies have identified that ZFHX4 antisense RNA 1 (ZFHX4-AS1) is aberrantly expressed in various cancers and is associated with poor outcomes. This study investigates whether ZFHX4-AS1 affects the prognosis of ACC patients and, if so, the potential mechanisms involved., Methods: In this study, utilizing four multi-center cohorts from The Cancer Genome Atlas (TCGA) program and Gene Expression Omnibus (GEO), we validated the prognostic capability of ZFHX4-AS1 in ACC patients through Kaplan-Meier survival analysis, cox regression models, and nomograms. Then, we explored the biological functions of ZFHX4-AS1 using gene set enrichment analysis (GSEA), competing endogenous RNA (ceRNA) networks, and analyses of somatic mutations and copy number variation (CNV). Finally, in vitro experiments were conducted to further validate the impact of ZFHX4-AS1 on proliferation and migration capabilities of ACC cell lines., Results: Survival analysis indicated that patients in the high ZFHX4-AS1 expression group of ACC had worse prognosis. Cox regression analyses suggested that ZFHX4-AS1 levels were independent risk factors for prognosis. Subsequently, we constructed nomograms based on clinical features and ZFHX4-AS1 levels, demonstrating good predictive performance under the time-dependent receiver operating characteristic (ROC) curve. Analysis based on somatic mutations and CNV revealed that CTNNB1 and 9p21.3-Del drove the expression of ZFHX4-AS1. Cell Counting Kit-8 (CCK-8), colony formation, and Transwell assays confirmed that knockdown of ZFHX4-AS1 inhibited proliferation and migration of ACC cells., Conclusions: This study demonstrates that ZFHX4-AS1 has a reliable predictive value for the prognosis of ACC patients and is a promising biomarker., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-649/coif). The authors have no conflicts of interest to declare., (2024 Translational Andrology and Urology. All rights reserved.)

Background: Adrenocortical carcinoma (ACC) is an extremely rare and highly invasive malignant tumor. However, there is currently no reliable method to predict the prognosis of ACC. Our objective is to construct a nomogram and a risk classification system to predict the 1-year, 3-year, and 5-year overall survival (OS) of ACC., Methods: We retrieved clinicopathological data of patients diagnosed with ACC in The Surveillance, Epidemiology, and End Results (SEER) database and divided them into training and validation cohorts with a 7:3 ratio. Simultaneously, we collected an external validation cohort from The First Affiliated Hospital of Naval Medical University (Shanghai, China). Univariate and multivariate Cox analyses were performed to identify relevant risk factors, which were then combined to develop a correlation nomogram. The predictive performance of the nomogram was evaluated using the concordance index (C-index), receiver-operating characteristic curve (ROC), and calibration curves. Decision curve analysis (DCA) was applied to assess the clinical utility of the nomogram. In addition, Kaplan-Meier survival curves were generated to demonstrate the variation in OS between groups., Results: The final nomogram consisted of five factors: age, T, N, M, and history of chemotherapy. Our prognostic model demonstrated significant discriminative ability, with C-index and the area under the receiver operating characteristic (AUC) values exceeding 0.70. Additionally, DCA validated the clinical utility of the nomogram. In the entire cohort, the median OS for patients in the low- and high-risk groups was 70 and 10 months, respectively., Conclusions: A nomogram and a corresponding risk classification system were developed in order to predict the OS of patients diagnosed with ACC. These tools have the potential to provide valuable support for patient counseling and assist in the decision-making process related to treatment options., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-571/coif). The authors have no conflicts of interest to declare., (2024 Translational Andrology and Urology. All rights reserved.)

Background: Adrenocortical carcinoma (ACC) is a rare endocrine neoplasia with poor prognosis. Emerging evidence suggests that kinesin family member 11 (KIF11) protein is overexpressed in several tumors and associated with the onset and progression of certain types of cancer; however, its biological functions and mechanisms in ACC progression have not been studied yet. Therefore, this study evaluated the clinical significance and therapeutic potential of the KIF11 protein in ACC., Methods: The Cancer Genome Atlas (TCGA) database (n=79) and Genotype Tissue Expression (GTEx) database (n=128) were utilized to explore the expression of KIF11 in ACC and normal adrenal tissues. The TCGA datasets were then data mined and statistically analyzed. R survival analysis and univariate and multivariate Cox regression analyses were used to evaluate the effect of KIF11 expression on the survival rates, and a nomogram was used to predict its impact on prognosis. The clinical data from 30 ACC patients' from Xiangya Hospital were also analyzed. The effects of KIF11 on the proliferation and invasion of ACC NCI-H295R were further validated in vitro ., Results: Analytical data from the TCGA and GTEx databases showed that KIF11 expression was upregulated in ACC tissues and associated with T (primary tumor), and M (metastasis) and stages of tumor progression. Increased KIF11 expression was significantly associated with shorter overall survival, disease-specific survival, and progression-free intervals. Clinical data from Xiangya Hospital illustrated that increased KIF11 had a significantly positive correlation with shorter overall survival, T and pathological stages, and tumor recurrence risk. Monastrol, a specific inhibitor of KIF11, was further confirmed to significantly inhibit the proliferation and invasion of ACC NCI-H295R cell in vitro . The nomogram demonstrated KIF11 was an excellent predictive biomarker in patients with ACC., Conclusions: The findings demonstrate that KIF11 could be a predictor of poor prognosis and thus possibly serve as a novel therapeutic target for ACC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-706/coif). XC reports the funding from Xiangya Clinical Data System of Central South University. The other authors have no conflicts of interest to declare., (2023 Translational Andrology and Urology. All rights reserved.)

Background: Adrenocortical carcinoma (ACC) is an extremely rare malignant tumor with poor prognosis. Existing treatment options have limited effects, and new therapeutic targets urgently need to be discovered. TNFSF13B has been reported to be associated with the prognosis of clear cell renal cell carcinoma, but it has not been studied in ACC., Methods: TNFSF13B expression was analyzed and compared between ACC tumors and normal tissues by using public datasets from TCGA and GTEx. Kaplan-Meier analysis was employed to evaluate survival, and Cox regression was employed to evaluate clinicopathologic features. The upstream and downstream regulatory mechanisms of TNFSF13B were also analyzed. GSEA was performed to explore the mechanisms of TNFSF13B in ACC. Finally, 14 ACC clinical samples were used to verify the relationships between TNFSF13B expression and disease-free survival (DFS) and overall survival (OS)., Results: TNFSF13B expression was significantly higher in ACC tissues than in normal tissues. The prognosis of ACC patients with high TNFSF13B expression was worse than that of patients with low TNFSF13B expression. High TNFSF13B expression was strongly correlated with poor prognosis, and TNFSF13B was a prognostic factor. TNFSF13B expression is modified by upstream miRNAs, methylation and ubiquitination, and downstream, it interacts with other proteins. GSEA showed that regulation of cholesterol biosynthesis by SREBP and SREBF, downstream signaling events of the B cell receptor (BCR) and activation of gene expression by SREBF and SREBP were significantly enriched in the TNFSF13B high-expression phenotype. Clinical samples confirmed that TNFSF13B expression was significantly associated with DFS but not with OS., Conclusions: TNFSF13B may be a potential prognostic molecular marker of poor survival in ACC patients, offering a new therapeutic target., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tau-21-232). The authors have no conflicts of interest to declare., (2021 Translational Andrology and Urology. All rights reserved.)

Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. Although laparoscopy has been widely adopted for management of benign adrenal tumors, minimally invasive surgery for ACC remains controversial. Retrospective analyses, frequently with fewer than one hundred participants, comprise the majority of the literature. High-quality data regarding the optimal surgical approach for ACC are lacking due to the rarity of the disease and the fact that determination of tumor type (e.g., adenoma or carcinoma) is determined after adrenalectomy, since adrenal tumors are generally not biopsied. While the benefits of minimally invasive surgery including lower intra-operative blood loss and decreased hospital length-of-stay have been consistently demonstrated, clinical equipoise for long-term survival and recurrence outcomes between open and minimally invasive adrenalectomy (MIA) remains. This review examines retrospective studies that directly compare patients with ACC who underwent either open or laparoscopic adrenalectomy, and considers these findings in the context of current guideline recommendations for surgical management of ACC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tau.2020.01.11). The series “Controversies in Minimally Invasive Urologic Oncology” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2021 Translational Andrology and Urology. All rights reserved.)

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., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tau-20-485). The authors have no conflicts of interest to declare., (2020 Translational Andrology and Urology. All rights reserved.)