Perspectives from machine learning and multi-omics to decoding the effects of VDAC2 malignant subsets on tumor evolution

Sep 23, 2026

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The study investigates how VDAC2 malignant subsets influence tumor evolution by integrating bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomic analyses across pan-cancers. VDAC2 is upregulated in most cancer types, with expression linked to immune infiltration, IFNγ signaling, and CD8+ T cell–mediated activity. Bioinformatics enrichment suggests roles in energy metabolism, mitochondrial damage, and cell proliferation, and a VDAC2-BAK1-IFNγ pathway is identified in digestive cancers. Functional validation in vitro confirms VDAC2 overexpression promotes gastric cancer proliferation, invasion, and immune invasion, supporting its value as a prognostic biomarker and therapeutic target.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Methodology and Results Summary

Systematic analysis of VDAC2 expression and localization

Biofunction enrichment analysis of VDAC2

npj | precision oncology Article | Published in partnership with The Hormel Institute, University of Minnesota | | | | --- | --- | --- | | [https://doi.org/10.1038/s41698-026-01394-1](https://doi.org/10.1038/s41698-026-01394-1) | | | | Perspectives from machine learning and multi-omics to decoding the effects of VDAC2 malignant subsets on tumor evolution
Check for updates | | | | Jianing Yan1,3, Jingzhi Wang2,3, Haotian Dong1, Guoliang Ye1 & Yongfu Shao1 | | | | VDAC2 ’s known role in cancer and immune regulation via enhancing the CD8+ T cell-mediated killing, and it is worth systematically digging out the roleofVDAC2 in pan-cancer based on this research. Bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomic analyses were utilized to explore the role ofVDAC2 from multiple perspectives in pan-cancers. RT-PCR, cell co-culture, CCK-8 assay, Transwell invasion assays, and ELISA were performed to validate the expression level and biological function. VDAC2 was upregulated in the majority of pan-cancers, and functional enrichment analyses displayed that VDAC2 may take part in the biological progress of energy metabolism, mitochondrial damage and cell proliferation. The landscape of VDAC2 expression and immune inﬁltration was constructed, and the VDAC2-BAK1-IFNγ pathway was identiﬁed in digestive cancer. VDAC2 had the potential to serve as a novel prognostic, screening cancer indicator and immune therapeutic target sensitive to various drugs. Overexpression of VDAC2 signiﬁcantly promoted gastric cancer cell proliferation, invasion and immune invasion, as validated in vitro experiments. In short, our pan-cancer analysis constructed a comprehensive landscape of VDAC2’s oncogenic role, establishing VDAC2 + -BAK1-IFNγ as an important pathway in tumor progression and immune evasion. VDAC2 emerges not only as a valuable prognostic biomarker but also as a promising novel therapeutic target. | | | | Voltage-Dependent Anion Channel 2 (VDAC2) is one of the relevant components ofthe outer mitochondrial membrane, playing a crucial role in recruiting BAK to mitochondria and restraining its activity at mitochondria1. As an important central regulator governing both cellular metabolism and apoptosis, VDAC2 occupies a critical position at the intersection of cancer and tumor microenvironment. In cancer pathogenesis, VDAC2 is frequently implicated in facilitating the characteristic metabolic shift towards heightened glycolytic ﬂux (the Warburg effect). Meanwhile, it confers resistance to apoptotic cell death, thereby promoting tumor cell survival and proliferation. Conversely, dysregulation or dysfunction of VDAC is increasingly recognized as a key contributor to mitochondrial impairment, which manifests as disrupted energy metabolism and perturbed calcium homeostasis. Ultimately, it can activate the pathogenic cell death pathways2. | Recently, a novel study pointed out that VDAC2 deﬁciency conspicuously elicited uncontrolled IFNγ-induced BAK activation and mitochondrial damage for improving cancer therapy via enhancing the CD8+ T cell-mediated killing in vitro and in vivo, which certainly increased our interest in exploring the novel roles of VDAC2 in cancers3. According to these evidence, bulk RNA sequencing, single-cell RNA sequencing(scRNAseq) and spatial transcriptomic analyses were utilized to explore the role of VDAC2from multiple perspectivesin pan-cancers(Fig. 1). Collectively, our study systematically explored and delineated the common oncogenic characteristics of VDAC2 across diverse tumor types and further identiﬁed associated drugs for tumor therapy and successfullyvalidated its biofunction role in gastric cancer. Compared with previous studies, our research is more comprehensive and provides an overall analysis of the role of VDAC2 in solid tumors from a broad cancer perspective. | | 1Department of Gastroenterology, The First Afﬁliated Hospital of Ningbo University, Ningbo, China. 2Department of

FAQs

What methods were used to analyze the role of VDAC2 in pan-cancers?

Bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomic analyses were used to explore VDAC2 across multiple tumor types. Experimental validations included RT-PCR, cell co-culture, CCK-8, Transwell invasion assays, and ELISA.

What key biological patterns were found for VDAC2 expression?

VDAC2 was upregulated in the majority of pan-cancers. High expression concentrated in immune subtypes with IFN-γ dominance, and VDAC2+ localization was enriched in tumor zones and associated with infiltrated immune cells.

Which signaling pathway related to VDAC2 was identified and what was its significance?

The VDAC2-BAK1-IFNγ pathway was identified in digestive cancer. The results also indicate VDAC2 involvement in energy metabolism, mitochondrial damage, cell proliferation, and immune evasion.

Sep 23, 2026

Uploaded by McGucket