Comprehensive pan-cancer investigation: unraveling the oncogenic, prognostic, and immunological significance of Abelson interactor family member 3 gene in human malignancies

Aijun Sun; Fengze Cai; Qingping Xiong; Tong Xie; Xiang Li; Yanteng Xie; Ruiyang Luo; Wenwen Hu; Fei Zhong; Shiyan Wang

doi:10.3389/fmolb.2023.1277830

Comprehensive pan-cancer investigation: unraveling the oncogenic, prognostic, and immunological significance of Abelson interactor family member 3 gene in human malignancies

Front Mol Biosci. 2023 Oct 24:10:1277830. doi: 10.3389/fmolb.2023.1277830. eCollection 2023.

Authors

Aijun Sun^#¹, Fengze Cai^#², Qingping Xiong^#³, Tong Xie², Xiang Li², Yanteng Xie², Ruiyang Luo³, Wenwen Hu⁴, Fei Zhong⁵, Shiyan Wang²

Affiliations

¹ Department of Thyroid and Breast Oncological Surgery, The Affiliated Huaian Hospital of Xuzhou Medical University and Huai'an Second People's Hospital, Huai'an, Jiangsu, China.
² School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huai'an, Jiangsu, China.
³ Jiangsu Key Laboratory of Regional Resource Exploitation and Medicinal Research, Huaiyin Institute of Technology, Huai'an, Jiangsu, China.
⁴ Third Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, China.
⁵ Department of Laboratory Medicine, The Affiliated Huaian Hospital of Xuzhou Medical University and Huai'an Second People's Hospital, Huai'an, Jiangsu, China.

^# Contributed equally.

Abstract

Background: Abelson interactor Family Member 3 (ABI3) encodes protein that not only suppresses the ectopic metastasis of tumor cells but also hinders their migration. Although ABI3 had been found to modulate the advancement of diverse neoplasms, there is no comprehensive pan-cancer analysis of its effects. Methods: The transcriptomics data of neoplasm and normal tissues were retrieved from the Genomic Data Commons (GDC) data portal, and UCSC XENA database. To gather protein information for ABI3, Human Protein Atlas (HPA) and GeneMANIA websites were utilized. Additionally, Tumor Immune Single-cell Hub (TISCH) database was consulted to determine the primary cell types expressing ABI3 in cancer microenvironments. Univariate Cox regression approach was leveraged to evaluate ABI3's prognostic role across cancers. The Cbioportal and Gene Set Cancer Analysis (GSCA) website were leveraged to scrutinize the genomic landscape information across cancers. TIMER2.0 was leveraged to probe the immune cell infiltrations associated with ABI3 across cancers. The associations of ABI3 with immune-related genes were analyzed through Spearman correlation method. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were utilized to search associated biological pathways. The CellMiner database and molecular docking were implemented to identify potential interactions between the ABI3 protein and specific anticarcinogen. Findings: ABI3 expression and its ability to predict prognosis varied distinct tumor, with particularly high expression observed in Tprolif cells and monocytes/macrophages. Copy number variation (CNV) and methylation negatively correlated with ABI3 expression in the majority of malignancies. Corresponding mutation survival analysis indicated that the mutation status of ABI3 was strongly connected to the prognosis of LGG patients. ABI3 expression was linked to immunotherapeutic biomarkers and response in cancers. ESTIMATE and immune infiltrations analyses presented ABI3 association with immunosuppression. ABI3 was significantly correlated with immunoregulators and immune-related pathways. Lastly, prospective ABI3-targeted drugs were filtered and docked to ABI3 protein. Interpretation: Our study reveals that ABI3 acts as a robust tumor biomarker. Its functions are vital that could inhibit ectopic metastasis of tumor cells and modulate cellular adhesion and migration. The discoveries presented here may have noteworthy consequences for the creation of fresh anticancer suppressors, especially those targeting BRCA.

Keywords: ABI3; immunotherapy; pan-cancer; prognostic biomarker; tumor immunity.

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by the Natural Science Foundation of Jiangsu Province (No. BK20210949) and Natural Science Research Program of Huai’an City (No. HAB202209).