Pediatric Adrenocortical Carcinoma Research Articles

Prognostic factors of adrenocortical carcinoma in children and adolescents: a population-based study.

Adrenocortical carcinoma (ACC) is an uncommon adrenal gland endocrine tumor that has a poor prognosis in children. We aimed toconducta population-based cohort study to predict overall survival (OS) in pediatric patients with ACC. We used the Surveillance, Epidemiology, and End Results (SEER) database to conduct a retrospective cohort research on pediatric patients diagnosed with ACC between 1975 and 2018.We examined demographic characteristics, tumor stage and size, treatment options, and survival results. Kaplane-Meier estimations were used to generate survival curves based on several parameters. To compare survival curves, the log-rank test was applied.Cox proportional-hazards regression was used to determine the variables related with OS. In addition, we created a nomogram to predict overall survival in pediatric ACC patients. A total of 143 pediatric ACC patients were identified. Females were the most impacted (60.8%). Overall 1year, 3year, and 5year survival rates were 75.0%, 57.6%, and 53.7% for all patients, respectively. In comparison to older patients (5-19years), younger patients (≤ 4years) were shown to have more positive characteristics, including a higher likelihood of local disease (29.4% vs. 14%, P < 0.001), tumors less than 10cm (23.1% vs. 14.7%, P < 0.001), and improved overall survival (5year OS 89.6% vs. 27.7%, P < 0.001). Age at diagnosis, SEER stage, and surgery were significant independent predictors of OS in this model, according to the results of Cox proportional hazard regression. After that, we developed a nomogram for predicting OS in children with ACC. Patients older than 4years old had a higher chance of dying. Furthermore, the higher the SEER stage, the higher the risk of death. Patients who do not have surgery have a worse survival rate than those who do. Our study revealed that age at diagnosis, SEER stage, and surgery were found to be the most important predictors of the overall survival of pediatric ACC. These findings contribute to the existing body of knowledge and emphasize the importance of continued research to advance our understanding of pediatric ACC and improve patient care.

Lamin B1: a novel biomarker in adult and pediatric adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a malignancy with a poor prognosis and high mortality rate. A high tumor mutational burden (TMB) has been found to be associated with poor prognosis in ACC. Thus, exploring ACC biomarkers based on TMB holds significant importance for patient risk stratification. In our research, we utilized weighted gene coexpression network analysis and an assay for transposase-accessible chromatin with high-throughput sequencing to identify genes associated with TMB. Through the comprehensive analysis of various public datasets, Lamin B1 (LMNB1) was identified as a biomarker associated with a high TMB and low chromatin accessibility. Immunohistochemical staining demonstrated high expression of LMNB1 in ACC compared to noncancerous tissues. Functional enrichment analyses revealed that the function of LMNB1 is associated with cell proliferation and division. Furthermore, cell assays suggested that LMNB1 promotes tumor proliferation and invasion. In addition, mutation analysis suggested that the high expression of LMNB1 is associated with TP53 mutations. Additionally, LMNB1 was highly expressed in the vast majority of solid tumors across cancers. In our immune analysis, we discovered that the high expression of LMNB1 might suppress the infiltration of CD8+ T cells in the ACC microenvironment. In summary, LMNB1 is a predictive factor for the poor prognosis of adult and pediatric ACC. Its high expression in ACC is positively associated with high TMB and lower chromatin accessibility, and it promotes ACC cell proliferation and invasion. Therefore, LMNB1 holds promise as a novel biomarker and potential therapeutic target for ACC.

Pediatric adrenocortical carcinoma revealed by isolated Cushing syndrome: A case report

Pediatric adrenocortical carcinoma revealed by isolated Cushing syndrome: A case report

Precocious puberty and other endocrine disorders during mitotane treatment for pediatric adrenocortical carcinoma - cases series

Precocious puberty and other endocrine disorders during mitotane treatment for pediatric adrenocortical carcinoma - cases series

Pediatric adrenocortical carcinoma: clinical features and application of neoadjuvant chemotherapy

ObjectiveTo summarize the clinical characteristics of children with adrenocortical carcinoma (ACC) and preliminarily explore the indications for and efficacy of neoadjuvant chemotherapy in certain patients.MethodsThe data of 49 children with adrenocortical tumors (ACT) in the past 15 years were retrospectively analyzed, and after pathology assessment using Weiss system grading, 40 children diagnosed with ACC were included. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and three-dimensional (3D) reconstruction of contrast-enhanced computed tomography data were used to evaluate the response to neoadjuvant chemotherapy.ResultsForty patients (17 males, 23 females) with ACC were enrolled. Abnormal hormone levels were common in children with ACC (n = 31), and in terms of clinical presentation, sexual precocity was the most common (n = 14, 35.0%), followed by Cushing’s syndrome (n = 12, 30.0%). Seven of 40 children received neoadjuvant chemotherapy due to a maximum lesion diameter greater than 10 cm (n = 4), invasion of surrounding tissues (n = 2), intravenous tumor thrombus (n = 2), and/or distant metastasis (n = 2); 2 patients achieved partial response, and 5 had stable disease according to the RECIST 1.1 standard. Furthermore, 3D tumor volume reconstruction was performed in 5 children before and after neoadjuvant chemotherapy. Tumor volumes were significantly reduced in all 5 children, with a median volume reduction of 270 (interquartile range, IQR 83, 293) (range: 49–413) ml. After surgery with/without chemotherapy, the 5-year overall survival rate for all children was 90.0% (95% CI-confidence interval 80.0–100.0%), and the 5-year event-free survival rate was 81.5% (95% CI 68.0–97.7%).ConclusionIn the diagnosis and treatment of pediatric ACC, a comprehensive endocrine evaluation is necessary to facilitate early diagnosis. Surgery and chemotherapy are important components of ACC treatment, and neoadjuvant chemotherapy should be considered for children with ACC who meet certain criteria, such as a large tumor, distant metastases, or poor general condition.

Ultrasonication-assisted synthesis of fluorescent borophene quantum dots for sensing of dehydroepiandrosterone biomarker

A novel fluorescence approach is introduced for sensing of dehydroepiandrosterone (DHEA). The primary characteristic of pediatric adrenocortical carcinoma disease causes due to the excessive production of DHEA, a hormone whose levels in the bloodstream can potentially facilitate the early diagnosis of cancer. In this paper, a water-dispersed borophene quantum dots (BQDs) based sensor was developed for the detection of DHEA, marking the first instance of such an application. The as-synthesized BQDs display blue fluorescence under 365 nm of UV light and exhibit λEx/Em at 370/428 nm with a good quantum yield of 24.12%. The as-prepared BQDs acted as a fluorescent “turn-on” sensor for the detection of DHEA with a dynamic range from 0.1 to 125 μM with the detection limit of 18.72 nM. The BQDs-based paper strip was designed for visual detection of DHEA. In addition, BQDs were utilized as imaging probes to visualize Saccharomyces cerevisiae cells. The developed method was extended for DHEA assay in biofluids (plasma and urine).

Abstract 1197: B7-H3-CAR T cells for the treatment of pediatric adrenocortical carcinoma

Abstract Outcomes for pediatric patients with unresectable, metastatic, or relapsed adrenocortical carcinoma (ACC) are dismal despite aggressive management with multimodality therapies. CAR T cell therapy (CAR T) is a promising approach to improve outcomes for patients with this disease. However, progress is hindered by a lack of targetable surface antigens and limited availability of relevant preclinical models. B7-H3 is a promising immunotherapeutic target but little is known about its expression in pediatric ACC. Thus, we sought to i) evaluate B7-H3 expression in primary pediatric ACC samples and ii) assess B7-H3-CAR T activity in two novel pediatric patient-derived xenograft (PDX) models. First, we assessed B7-H3 expression in 44 pediatric adrenocortical tumors (ACTs) using a CLIA-approved immunohistochemistry (IHC) assay. ACTs had a range of B7-H3 positivity, including 24 (55%) with expression above the threshold for eligibility on our active B7-H3-CAR T clinical trial (H-score ≥ 100; NCT04897321). Univariate analyses demonstrated B7-H3 expression was correlated with the presence of germline TP53 mutations and poor prognostic factors including the inability to achieve complete resection, Cushing phenotype, and the absence of TP53 by IHC. Given a dearth of in vivo models, we next established two clinically relevant pediatric ACC PDX models. SJ-ACC4 was derived from a metastatic tumor and had somatic mutations in TP53 (p.C135Lfs*14) and CTNNB1 (p.S45F). SJACT030812_X1 (www.stjude.org/cstn) was derived from a primary tumor and had a germline TP53 mutation (p.R110Pfs*39). Both had partial ATRX deletions (exons 11-30; 3-28), uniparental disomy at chromosome 11p15, and were B7-H3-positive. Notably, SJ-ACC4 was resistant to a battery of chemotherapeutic agents. To evaluate B7-H3-CAR T anti-ACC activity in vivo, SJ-ACC4 tumor fragments were implanted subcutaneously in NOD SCID gamma (NSG) mice and treated with B7-H3-CAR or control T cells. Strikingly, B7-H3-CAR T eradicated 100% of SJ-ACC4 tumors and mice survived long term compared to controls that met endpoints within 35 days (n=8 per group, p&amp;lt; 0.0001). Finally, we asked if B7-H3-CAR T had antitumor activity in an orthotopic pediatric ACC PDX model. SJACT030812_X1 cells were injected into the para-adrenal region of NSG mice under ultrasound guidance and monitored by serial volumetric ultrasonography. B7-H3-CAR T again had significant antitumor activity, and mice survived long-term compared to controls that met endpoints within 42 days (n=5 per group, p&amp;lt; 0.01). In conclusion, B7-H3 is expressed in a majority of pediatric ACTs and B7-H3-CAR T have potent anti-ACC activity. These findings provide a strong rationale for clinically evaluating B7-H3-CAR T for pediatric patients with chemotherapy-resistant ACC. Additionally, the newly established pediatric ACC PDX models provide a valuable resource for investigating different aspects of this rare and aggressive disease. Citation Format: Rebecca Epperly, Emilia M. Pinto, Teresa Santiago, Heather Sheppard, Michael R. Clay, Christopher Morton, Phuong Nguyen, Yinmei Zhou, Mary Woolard, Carla O'Reilly, Julie Justice, Walter Akers, Melissa Johnson, Asa Karlstrom, Cheng Cheng, Gerard Zambetti, Andrew Davidoff, Raul Ribeiro, Christopher DeRenzo. B7-H3-CAR T cells for the treatment of pediatric adrenocortical carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1197.

Effects of o,p'-DDE, a Mitotane Metabolite, in an Adrenocortical Carcinoma Cell Line.

In South Brazil, the incidence of pediatric adrenocortical carcinoma (ACC) is higher than in other regions and countries worldwide. The ACC treatment includes therapy with mitotane, the only adrenolytic drug approved by the FDA. The mitotane metabolism occurs via two main reactions: the β-hydroxylation, which yields the final product o,p'-DDA, and the α-hydroxylation, which will give the final product o,p'-DDE. It is speculated that o,p'-DDE may be an active metabolite since it has a cytotoxic effect on adrenocortical carcinoma cells (H295R). No further studies have been conducted to confirm this hypothesis; however, it was found that mitotane and its metabolites are present at significantly different concentrations in the plasma of the patients. Our study aimed to assess the in vitro effects of o,p'-DDE and o,p'-DDD in cell death pathways, oxidative parameters, and interaction with adrenal CYP's involved in the steroidogenic process in the H295R cell line. It was found that o,p'-DDE had a different effect than the o,p'-DDD on apoptosis, inhibiting this cell death pathway, but it promotes cell necrosis at higher concentrations. In contrast to o,p'-DDD, the o,p'-DDE did not have effects on the different oxidative parameters evaluated, but exhibited stimulatory interactions with steroidogenic CYP's, at intermediate concentrations. Therefore, we demonstrated important cell effects of o,p'-DDE; its plasma levels during mitotane therapy should be monitored as an important therapeutic parameter.

Pediatric adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy of the adrenal gland with an unfavorable prognosis. It is rare in the pediatric population, with an incidence of 0.2-0.3 patients per million in patients under 20 years old. It is primarily associated with Li-Fraumeni and Beckwith-Wiedemann tumor predisposition syndromes in children. The incidence of pediatric ACC is 10-15fold higher in southern Brazil due to a higher prevalence of TP53 mutation associated with Li-Fraumeni syndrome in that population. Current treatment protocols are derived from adult ACC and consist of surgery and/or chemotherapy with etoposide, doxorubicin, and cisplatin (EDP) with mitotane. Limited research has been reported on other treatment modalities for pediatric ACC, including mitotane, pembrolizumab, cabozantinib, and chimeric antigen receptor autologous cell (CAR-T) therapy.

Adrenocortical carcinoma: Pediatric aspects (Review).

Adrenocortical carcinoma (adrenal cortex-derived cancer), an orphan malignancy, is a very aggressive disease that affects both adults and children with an annual incidence of 1-2 adult and 0.2-0.38 pediatric cases/million (in the pediatric population it represents 0.2% of all cancers), with a female predominance. A total of 80-90% of cases have hormonal imbalances such as Cushing syndrome, virilization, and puberty anomalies. Precocious puberty (PP) of iso- or hetero-sexual pattern is independent of gonadotropin-releasing hormone (GnRH) (high testosterone/estrogens and low FSH/LH) but post-operative activation of GnRH may be expected (central PP). PP is accompanied by accelerated growth while Cushing syndrome by reduced growth velocity. Pure androgen-secreting tumors have been exceptionally described. A total of 50-80% of children have different genetic/epigenetic anomalies involving tumor protein p53 (most often, almost half of the cases; with a population cluster in Southern Brazilian children), insulin-like growth factor, multiple endocrine neoplasia type 1 (MEN1), PRKAR1A, dysfunctional alternative lengthening of telomeres. Hereditary syndromes associated to adrenocortical carcinoma include Li-Fraumeni, Beckwith-Wiedemann, MEN1, and Lynch. Recently, mutations in epidermal growth factor receptor have been reported in teenagers, suggesting the future use of tyrosine kinase inhibitors. Adrenalectomy is the first line therapy offering the best prognosis if complete tumor removal is achieved; genetic testing is recommended before surgery. Adjuvant therapies are less standardized in children (mitotane is a key adjuvant drug in addition with different regimes of chemotherapy such as etoposide, Adriamycin and cisplatin). A Ki-67 value of at least 15% is a predictor of poor outcome. Weiss score also serves as a prognostic factor, as well as the tumor size at diagnosis. The prognosis of adrenocortical carcinoma is poor with an overall 5-year survival rate of 55%; a Weiss score of at least 6 is associated with a 2-year survival rate of 35%. At present, pediatric adrenocortical carcinoma still represents a severe condition that requires prompt intervention and a multidisciplinary team. Further development of molecular markers is required for an improved understanding of the disease thus improving the protocols of approach and the prognostic.

Malignant Adrenal Cortex in Children: About 6 Cases

The pediatric adrenocortical carcinoma is a rare cancer estimated at 0.3-0.38 cases per million children per year. its diagnosis is based on a set of clinical, biological and radiological arguments. Its rarity, coupled with a relatively poor literature, especially from a prospective point of view, make the therapeutic approach to this cancer a real challenge. This work identifies 6 patients who were treated in the pediatric surgery department A of the children's hospital in Rabat over a period of 28 years, and aims to shed light on the various clinical, biological and radiological aspects of malignant adrenocortical carcinoma, as well as different therapies used and the outcome of these children; and offers a comparative approach with what the literature offers.

Adrenocortical Carcinoma in Childhood: A Systematic Review.

Simple SummaryPediatric adrenocortical tumors are rare. Little information is available on the incidence, risk factors, prognostic factors, treatment, and overall survival. In this systematic review, we performed a search of the current literature. The most common reported risk factors are age > 4 years, high pathological tumor score, and advanced stage in which prognosis is poor. Treatment options are surgery, radiation, or chemotherapy, but ongoing randomized trials are lacking. International prospective studies must be the next step to implement standardized clinical stratifications and risk-adapted therapeutic strategies.Adrenocortical tumors are rare in children. This systematic review summarizes the published evidence on pediatric adrenocortical carcinoma (ACC) to provide a basis for a better understanding of the disease, investigate new molecular biomarkers and therapeutic targets, and define which patients may benefit from a more aggressive therapeutic approach. We included 137 studies with 3680 ACC patients (~65% female) in our analysis. We found no randomized controlled trials, so this review mainly reflects retrospective data. Due to a specific mutation in the TP53 gene in ~80% of Brazilian patients, that cohort was analyzed separately from series from other countries. Hormone analysis was described in 2569 of the 2874 patients (89%). Most patients were diagnosed with localized disease, whereas 23% had metastasis at primary diagnosis. Only 72% of the patients achieved complete resection. In 334 children (23%), recurrent disease was reported: 81%—local recurrence, 19% (n = 65)—distant metastases at relapse. Patients < 4 years old had a different distribution of tumor stages and hormone activity and better overall survival (p < 0.001). Although therapeutic approaches are typically multimodal, no consensus is available on effective standard treatments for advanced ACC. Thus, knowledge regarding pediatric ACC is still scarce and international prospective studies are needed to implement standardized clinical stratifications and risk-adapted therapeutic strategies.

3 QUESTIONS ON... Optimizing Treatment for Pediatric Adrenocortical Carcinoma

3 QUESTIONS ON... Optimizing Treatment for Pediatric Adrenocortical Carcinoma

Survival characteristics of localized pediatric adrenocortical carcinoma managed with adenectomy: A national cancer center database analysis

Pediatric adrenocortical carcinoma (ACC) is a rare malignancy, encompassing less than 0.2% of all childhood malignancies. Due to the scarcity of this diagnosis, it is often managed according to guidelines established for adults, as there is a lack of reliable evidence regarding optimal adjuvant treatment options for pediatric patients. It is our aim to identify recent treatment trends as well as clinical and tumor characteristics and their impact on overall survival. Using the National Cancer Data Base (NCDB), this study identified 49 patients under 18 years old with localized ACC (M0) undergoing adrenalectomy from 2004 to 2017. Kaplan-Meier analysis was performed to determine overall survival (OS) from patient characteristics and treatments received. Comparison of survival was performed using the log rank test. The median age of our cohort was 3 years old with a slight female predominance of 61%. The median tumor size was 9.4cm, and patients older than 4 years were significantly (p=0.03) more likely to present with larger tumors (11.33cm vs 8.76cm). Adjuvant treatment in the form of systemic therapy was administered in 20 of 49 (41%) patients and radiation therapy in 2 of 49 (4%) patients. Three-year OS for patients 4 years old and younger was 92.6% vs 61.8% for those older than 4 years (p=0.002). Patients presenting with tumor size ≥9cm had worse three-year OS compared to those with tumors <9cm (95.24% vs 67.1% respectively, p=0.02, Fig. 1). In patients with tumors≥9cm, younger children age 0-4 years had significantly (p=0.04) higher OS rates than older children age 5-17 years. ACC is a rare pediatric malignancy with a female predominance. Those older than 4 years and those with presenting tumor size ≥9cm have decreased overall survival rates after adrenalectomy for localized disease. Additionally, children older than 4 have poorer prognosis, even after controlling for larger tumor size. This is the largest contemporary series of localized pediatric ACC to date. However, multi-institutional prospective cohort or randomized-controlled trials are necessary to better evaluate relevant prognostic factors and the role of adjuvant therapies following adrenalectomy.

Penetrance of the TP53 R337H Mutation and Pediatric Adrenocortical Carcinoma Incidence Associated with Environmental Influences in a 12-Year Observational Cohort in Southern Brazil.

The TP53 R337H mutation is associated with increased incidence of pediatric adrenocortical tumor (ACT). The different environmental conditions where R337H carriers live have not been systematically analyzed. Here, the R337H frequencies, ACT incidences, and R337H penetrance for ACT were calculated using the 2006 cohort with 4165 R337H carriers living in Paraná state (PR) subregions. The effectiveness of a second surveillance for R337H probands selected from 42,438 tested newborns in PR (2016 cohort) was tested to detect early stage I tumor among educated families without periodical exams. Estimation of R337H frequencies and ACT incidence in Santa Catarina state (SC) used data from 50,115 tested newborns without surveillance, ACT cases from a SC hospital, and a public cancer registry. R337H carrier frequencies in the population were 0.245% (SC) and 0.306% (PR), and 87% and 95% in ACTs, respectively. The ACT incidence was calculated as ~6.4/million children younger than 10 years per year in PR (95% CI: 5.28; 7.65) and 4.15/million in SC (CI 95%: 2.95; 5.67). The ACT penetrance in PR for probands followed from birth to 12 years was 3.9%. R337H carriers living in an agricultural subregion (C1) had a lower risk of developing pediatric ACT than those living in industrial and large urban subregion (relative risk = 2.4). One small ACT (21g) without recurrence (1/112) was detected by the parents in the 2016 cohort. ACT incidence follows R337H frequency in each population, but remarkably environmental factors modify these rates.

Pediatric vs Adult Adrenocortical Carcinoma: Different Rate of Surgical Treatment and Patient Outcome

Pediatric vs Adult Adrenocortical Carcinoma: Different Rate of Surgical Treatment and Patient Outcome

Pediatric Mixed Functioning Adrenocortical Carcinoma: A Case Report and Review of Literature

Adrenocortical carcinoma (ACC) is a very rare disease in the pediatric age group. The clinic-biological profile, histopathological criteria of diagnosis, and staging of this disease in this age group are different from those of adult ACC. In this paper, we report a case of pediatric ACC presenting as Cushing syndrome that was managed with complete surgical excision. Through this case presentation, we highlight the sequential protocol of investigations and management in a child suspected of having ACC.

Label-free impedimetric immunosensor based on arginine-functionalized gold nanoparticles for detection of DHEAS, a biomarker of pediatric adrenocortical carcinoma

Pediatric adrenocortical carcinoma (pACC) is a rare and aggressive malignancy of high occurrence in Southern Brazil. pACC is characterized by the usual overproduction of dehydroepiandrosterone sulfate (DHEAS), whose detection in serum or plasma can be effective to the early diagnosis of the disease. Therefore, the present paper reports, for the first time, the construction and application of a label-free impedimetric immunosensor to detect DHEAS, which was based on the modification of an oxidized glassy carbon electrode with arginine-functionalized gold nanoparticles (AuNPs-ARG) and anti-DHEA IgM antibodies (ox-GCE/AuNPs-ARG/IgM). AuNPs-ARG was synthesized by a green route, and characterized by UV–VIS spectroscopy, FTIR, TEM, DLS, and XRD. The construction of ox-GCE/AuNPs-ARG/IgM was optimized through factorial design and response surface methodology. Cyclic voltammetry and electrochemical impedance spectroscopy measurements were employed to characterize the optimized immunosensor. The DHEAS detection principle was based on the variation of charge transfer resistance (∆Rct) relative to the Fe(CN)64−/3− electrochemical probe after immunoassays in the presence of the biomarker. A linear relationship between ∆Rct and DHEAS concentration was verified in the range from 10.0 to 110.0 µg dL−1, with a LOD of 7.4 µg dL−1. Besides the good sensitivity, the immunosensor displayed accuracy, stability, and specificity to detect DHEAS. The promising analytical performance of ox-GCE/AuNPs-ARG/IgM was confirmed by quantifying DHEAS in real patient plasma samples, with results that were comparable to the reference chemiluminescence assay. Our results suggest that the presented immunosensor can find clinical applications in the early diagnosis of pACC and to monitor DHEAS levels in other adrenal pathologies.

Biomolecular engineering of antidehydroepiandrosterone antibodies: a new perspective in cancer diagnosis and treatment using single-chain antibody variable fragment.

To develop a monoclonal antibody against dehydroepiandrosterone (DHEA) and miniaturize it, generating a single-chain antibody variable fragment (scFv) against DHEA as an adrenocortical carcinoma (ACC) marker. DHEA conjugated to keyhole limpet hemocyanin was used as an immunogen to obtain anti-DHEA hybridomas. Variable fragments were cloned from hybridoma 5B7 total RNA, and used to detect DHEA in normal adrenal tissue and ACC cells. IgM monoclonal antibody was highly specific, and the recombinant scFv preserved parental antibody characteristics, allowing tissue localization of DHEA. Undefined small lesions are challenges for clinicians and impact clinical adrenocortical tumor management. Generating an anti-DHEA scFv facilitates development of imaging tests for early diagnosis of pediatric ACC.

Common module analysis reveals prospective targets and mechanisms of pediatric adrenocortical adenoma and carcinoma.

Pediatric adrenocortical carcinoma and adrenocortical adenoma are two rare diseases affecting children. Molecular analyses were performed to identify commonalities in gene expression between the diseases. Differentially expressed genes were identified for the pediatric adrenocortical adenoma and carcinoma tissues, as compared with normal tissues, using the expression dataset. Protein-protein interaction (PPI) networks were constructed for adenoma and carcinoma disease models, and common modules among the diseases were identified. A total of two common modules with 14 nodes and 20 nodes were revealed among the adenoma and carcinoma networks, respectively. Genes of the common modules were also identified to be the common hub genes of the disease models. Enrichment of the genes of the common modules suggested associations with steroid biosynthesis, the proteasome, cell cycle and metabolic pathways. Modularity, topological and functional analysis of the PPI networks revealed common modules among pediatric adenoma and carcinoma disease models, which provided insight into the underlying disease mechanisms and suggesting prospective targets for future study.