ArticleCancer research2022
Spatial Transcriptomic Analysis of Ovarian Cancer Precursors Reveals Reactivation of IGFBP2 during Pathogenesis.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Tubal epithelial alterations: evolving concepts.Journal of gynecologic oncology · 2026Review
- Spatial transcriptomics in cancer research: insights into tumorigenesis, diagnosis and therapeutics.Cell death discovery · 2026Review
- Understanding the spatial determinants of the Oxford Classic prognostic signature for high-grade serous ovarian cancer.Communications medicine · 2026Article
- miR-130b-5p Regulates Expression of ERβ via IGFBP2/SREBP1 Axis in Human Endometriotic Stromal Cells.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Spatial proteomics of ovarian cancer precursors delineates early disease changes and drug targets.Molecular systems biology · 2026Article
- Integrating multi-omics and clinical features to model survival in epithelial ovarian cancer subtypes.Scientific reports · 2025Article
- Spatial omics: applications and utility in profiling the tumor microenvironment.Cancer metastasis reviews · 2025Review
- XPR1 promotes ovarian cancer growth and regulates MHC-I through autophagy.Genes & diseases · 2025Article
- Integrated Spatial Analysis of Ovarian Precancerous Lesions.bioRxiv : the preprint server for biology · 2025Article
- DCIS Progression and the Tumor Microenvironment: Molecular Insights and Prognostic Challenges.Cancers · 2025Review
- A comprehensive overview of ovarian cancer stem cells: correlation with high recurrence rate, underlying mechanisms, and therapeutic opportunities.Molecular cancer · 2025Review
- Mutant PP2A Induces IGFBP2 Secretion to Promote Development of High-Grade Uterine Cancer.Cancer research · 2025Article
- A cell atlas of the human fallopian tube throughout the menstrual cycle and menopause.Nature communications · 2025Article
- Serous tubal intraepithelial carcinoma-looking into the earliest events of ovarian cancer development.Academia oncology · 2025Article
- Article
- Combined assembloid modeling and 3D whole-organ mapping captures the microanatomy and function of the human fallopian tube.Science advances · 2024Article
- Age-Related Increases in IGFBP2 Increase Melanoma Cell Invasion and Lipid Synthesis.Cancer research communications · 2024Article
- Spatial transcriptomics in cancer research and potential clinical impact: a narrative review.Journal of cancer research and clinical oncology · 2024Review
- Review
- Advances in the role of GPX3 in ovarian cancer (Review).International journal of oncology · 2024Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Elucidating the earliest pathogenic steps in cancer development is fundamental to improving its early detection and prevention. Ovarian high-grade serous carcinoma (HGSC), a highly aggressive cancer, mostly originates from the fallopian tube epithelium through a precursor stage, serous tubal intraepithelial carcinoma (STIC). In this study, we performed spatial transcriptomic analysis to compare STICs, carcinoma, and their matched normal fallopian tube epithelium. Several differentially expressed genes in STICs and carcinomas were involved in cancer metabolism and detected in a larger independent transcriptomic dataset of ovarian HGSCs. Among these, insulin-like growth factor binding protein-2 (IGFBP2) was found to undergo DNA hypomethylation and to be increased at the protein level in STICs. Pyrosequencing revealed an association of IGFBP2 expression with the methylation state of its proximal enhancer, and 5-azacytidine treatment increased IGFBP2 expression. In postmenopausal fallopian tubes, where most STICs are detected, IGFBP2 immunoreactivity was detected in all 38 proliferatively active STICs but was undetectable in morphologically normal tubal epithelia, including those with TP53 mutations. In premenopausal fallopian tubes, IGFBP2 expression was limited to the secretory epithelium at the proliferative phase, and estradiol treatment increased IGFBP2 expression levels. IGFBP2 knockdown suppressed the growth of IGFBP2-expressing tubal epithelial cells via inactivation of the AKT pathway. Taken together, demethylation of the proximal enhancer of IGFBP2 drives tumor development by maintaining the increased IGFBP2 required for proliferation in an otherwise estrogen-deprived, proliferation-quiescent, and postmenopausal tubal microenvironment. SIGNIFICANCE: Molecular studies of the earliest precursor lesions of ovarian cancer reveal a role of IGFBP2 in propelling tumor initiation, providing new insights into ovarian cancer development.
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