Clinic al Journal of pharmacology
Letter
@2025 Dustri-Verlag Dr. K. Feistle ISSN 0946-1965
DOI 10.5414/CP204767 e-pub: July 22, 2025
Cao C, Li X, Feng X, Wang Y. High expression of EFNA3 in adrenocortical carcinoma and its association with prognosis. Int J Clin Pharmacol Ther. 2025; 63: 493-495.
DOI 10.5414/CP204767
citation
LETTER TO THE EDITOR
High expression of EFNA3 in adrenocortical carcinoma and its association with prognosis
Caihong Cao1, Xiao Li2, Xing Feng3, and Yansha Wang4
1Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 2Department of Oncology, Linfen Central Hospital, Linfen, 3Department of Orthopaedics, Lvliang First People’s Hospital, Lvliang, and 4Department of Pathology, Jincheng People’s Hospital, Jincheng, Shanxi Province, China
Sir, - Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy with an annual incidence of 0.7 - 2 cases per mil- lion and a 5-year survival rate below 35% [1, 2, 3, 4, 5]. Surgery remains the primary treatment for localized ACC, but recurrence rates range from 19% to 34%, and adjuvant therapies have shown limited efficacy [6, 7]. Identifying prognostic biomarkers is crucial for improving treatment strategies.
Ephrins are cell surface ligands that in- teract with Eph receptors to regulate cell migration, adhesion, and angiogenesis [8]. Dysregulated ephrin expression is linked to tumor invasion, metastasis, and poor prog- nosis [9].
This study analyzed clinical features, prognosis, and immune infiltration in ACC patients using multiple online databases to identify key genes influencing ACC progres- sion, with a focus on EFNA3, a member of the ephrin family, and its potential role in tu- mor development and immune interactions.
We utilized several databases for gene expression and clinical data analysis in this study. The GEPIA database provided tumor and normal tissue samples from TCGA and GTEx, enabling expression and pathological stage analysis of EFNA3 in ACC. Prognostic value assessments of EFNA3 expression in- cluded overall survival (OS) and disease-free survival (DFS). The TISIDB database offered insights into EFNA3 expression across dif- ferent molecular subtypes of ACC. Data from TCGA and GTEx were used to examine EFNA3 expression in ACC tissues versus nor-
mal adrenal glands, with differential expres- sion identified via EdgeR. Clinical data from TCGA further facilitated correlation analysis between EFNA3 expression and clinicopath- ological characteristics. Additionally, GEO database RNA sequencing data (GSE10927) was analyzed for EFNA3 transcription levels.
EFNA3 was found to be highly expressed in several tumor types, including ACC, with increased mRNA levels compared to nor- mal tissues. In the TCGA cohort, its expres- sion correlated significantly with various clinicopathological parameters, such as tu- mor status, pathologic stage, and primary therapy outcomes. Co-expression analysis identified genes related to cell structure, de- velopment, and the P53 signaling pathway. Protein-Protein Interaction Networks analy- sis revealed associations between EFNA3 and Ephrin receptors, such as EPHA4 and EPHA2, suggesting a role in tumor develop- ment (Figure 1).
Further immune analysis showed that EFNA3 expression negatively correlated with CD8+ T cells and macrophages, but posi- tively correlated with tumor purity. It was also linked to immune markers for various cell types, including B cells, T cells, macro- phages, and NK cells. EFNA3 expression was associated with distinct immune infiltration patterns, with higher EFNA3 levels correlat- ing with decreased immune cell populations, such as CD8+ T cells and macrophages.
Additionally, a ceRNA network involving EFNA3 was constructed, identifying 12 tar- get miRNAs, some of which were negatively
p = 8.47e-01
0.52
0.53
A
EFNA3 Expression Level (log2 TPM)
Purity
B Cell
CDB+ T Cell
CD4+ T Cell
Macrophage
Neutrophil
Dendritic Cell
15
cor = 0.683
p = 2.06e-11
partial.cor = 0.12
p = 3.13e-01
partial.cor = - 0.231
p = 4.88e-02
partial.cor =- 0.058
p = 6.27e-01
partial.cor =- 0.243
p = 3.79e-02
partial.cor =- 0.103
p = 3.85e-01
partial.cor = - 0.023
10-
5
ACC
0-
5
0.2
0.4
0.6
0.8
1.0
0.11
0.12
0.13
0.20
0.25
0.30
0.35 0.07
0.09
0.11
0.13
0.15
0.08
0.12
0.16
0.12
0.14
0.16
0.18
0.49
0.50
0.51
Infiltration Level
B
ACC
*
*
*
Infiltration Level
0.5
0.4
Copy Number
0.3
Arm-level Deletion
Diploid/Normal
Arm-level Gain
0.2
High Amplication
0.1
B Cell
CD8+ T Cell
CD4+ T Cell
Macrophage
Neutrophil
Dendritic Cell
C
EFNA3 Ę
Low
฿
High
0.8
ns
…
ns
ns
…
ns
**
ns
CIBERSORT Scores
0.6
0.4
0.2
:
0.0
-0.2
aDC
B cells
CD8 T cells
Cytotoxic cells
DC
Eosinophils
IDC
Macrophages
Mast cells
Neutrophils
NK CD56bright cells
NK CD56dim cells
NK cells
PDC
T cells
T helper cells
Tcm
Tem
TFH
Th1 cells
Th17 cells
Tgd
Th2 cells
TReg
Cao C, Li X, Feng X, Wang Y. High expression of EFNA3 in adrenocortical carcinoma and its association with prognosis. Int J Clin Pharmacol Ther. 2025; 63: 493-495.
DOI 10.5414/CP204767
citation
correlated with EFNA3 expression, providing insights into potential regulatory mecha- nisms.
EFNA3, a membrane protein, is highly ex- pressed in ACC and shows a strong associa- tion with immune infiltration and prognosis. Our analysis indicates that EFNA3 expression correlates with immune markers in T cells, macrophages, and dendritic cells in ACC, suggesting its involvement in tumor pro- gression, immune regulation, and metasta- sis [10]. EFNA3 is known to influence cancer cell proliferation, angiogenesis, and immune cell behavior, and its overexpression in vari- ous cancers correlates with poor prognosis [11]. In ACC, high EFNA3 levels are linked to adverse clinical outcomes and immune cell
infiltration. The findings suggest that EFNA3 could serve as both a prognostic biomarker and a potential therapeutic target for ACC. While further validation through clinical ex- periments is needed, this study highlights the promise of EFNA3 in improving the di- agnosis and treatment of ACC. Its expression profiles may guide therapeutic decisions and provide new avenues for drug development.
Availability of data and materials
All relevant data to this case is reported in the manuscript.
Authors’ contributions
Caihong Cao designed the study and drafted and edited the manuscript. Xiao Li collected, interpreted, and analyzed the data. Xing Feng drafted and edited the man- uscript. Yansha Wang conceptualized the study and edited the manuscript. All authors read and approved the final draft.
Funding
No external funding was received to con- duct this study.
Conflict of interest
The authors declare that they have no competing interests.
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Correspondence to Yansha Wang, MM Department of Pathology Jincheng People’s Hospital No. 456 Wenchang East Street Jincheng City, 048026, China wangyanshawysm@126.com
Cao C, Li X, Feng X, Wang Y. High expression of EFNA3 in adrenocortical carcinoma and its association with prognosis. Int J Clin Pharmacol Ther. 2025; 63: 493-495.
DOI 10.5414/CP204767
citation