Loading
Bone Metabolism and Diseases / Peroxisome Proliferator-activated Receptors · Journal article
Frontiers in Pharmacology · August 24, 2026
Encouraging direction, but not yet definitive.
This integrative study identifies PPAP2C as significantly overexpressed in breast cancer, independently associated with worse overall and disease-free survival across multiple cohorts, and demonstrates oncogenic function in TNBC cells and xenografts. While the prognostic biomarker evidence is solid and multi-validated, therapeutic target claims remain at the preclinical stage without human efficacy data.
Integrated multi-omics analysis with confirmatory survival analyses and functional validation. Breast cancer patients across TCGA, METABRIC, and GEO cohorts; triple-negative breast cancer (TNBC) cell lines; tissue microarray samples from tumor and adjacent normal tissues; MDA-MB-231 xenograft-bearing mice. Intervention: PPAP2C knockout via CRISPR-Cas9-mediated frameshift mutations (5-bp/1-bp), or ectopic PPAP2C overexpression in TNBC cells; in vivo PPAP2C knockout in MDA-MB-231 xenografts. Compared with: PPAP2C wild-type control cells; control xenografts; normal breast tissues for protein expression comparison.
PPAP2C upregulated in 16 of 33 cancer types, downregulated in only 3, with specific overexpression in breast cancer tissues versus normal tissues High PPAP2C expression correlated with significantly shorter overall survival and disease-free survival, validated in TCGA, METABRIC, and GEO cohorts Tissue microarray analysis showed higher PPAP2C protein positivity in tumor tissues (94.7%) compared with adjacent normal tissues (59.7%), with worse OS and RFS in high-expression groups
No pharmacological inhibitor of PPAP2C tested; functional studies relied on genetic manipulation only
PPAP2C expression measured by IHC may stratify breast cancer patients at high risk of recurrence and death, particularly in aggressive subtypes. However, therapeutic targeting of PPAP2C remains unvalidated clinically and should not guide treatment decisions outside research settings until human efficacy and safety data emerge.
Integrative multi-omics study with confirmatory survival analyses across multiple cohorts and mechanistic validation in TNBC cells and xenografts, but lacks clinical trial evidence and therapeutic efficacy data in vivo.
As stated by the source record.
Quoted from the source exactly as published.
PPAP2C expression measured by IHC may stratify breast cancer patients at high risk of recurrence and death, particularly in aggressive subtypes. However, therapeutic targeting of PPAP2C remains unvalidated clinically and should not guide treatment decisions outside research settings until human efficacy and safety data emerge.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Background This study aims to systematically elucidate the clinical significance and biological function of the phospholipid phosphatase (PLPP) family member (PPAP2C) phosphatidic acid phosphatase type 2C in breast cancer, and to evaluate its potential as a prognostic biomarker and therapeutic target. Methods Gene expression data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases were integrated to characterize the expression profile of PLPP family members, focusing on PPAP2C in breast cancer. The prognostic value of PPAP2C, initially identified at the mRNA level (TCGA, (METABRIC) Molecular Taxonomy of Breast Cancer International Consortium, Gene Expression Omnibus (GEO)), was confirmed at the protein level by immunohistochemistry (IHC) on tissue microarrays (TMA). The oncogenic functions of PPAP2C were investigated in triple-negative breast cancer (TNBC) cells through CRISPR-Cas9-mediated knockout and ectopic overexpression, with assessment of key phenotypes including proliferation, colony formation, migration, and invasion. In vivo validation was subsequently performed using an MDA-MB-231 xenograft model. Results PPAP2C exhibits the most significant overexpression pattern across 33 cancer types (upregulated in 16 cancers, downregulated in only 3). Compared with normal tissues, PPAP2C showed specific overexpression in breast cancer tissues and was significantly associated with advanced clinical stages and aggressive subtypes (HER2 + and TNBC). Survival analysis demonstrated that high PPAP2C expression correlated with significantly shorter overall survival and disease-free survival, which was further validated in METABRIC and GEO cohorts. Tissue microarray analysis confirmed higher PPAP2C protein positivity in tumor tissues (94.7%) than in adjacent normal tissues (59.7%), with worse OS and RFS in high-expression groups. Multivariate analysis identified PPAP2C as an independent prognostic factor for OS. Functional experiments revealed that PPAP2C knockout (via 5-bp/1-bp frameshift mutations) suppressed TNBC cell proliferation, colony formation, migration, and invasion, while overexpression enhanced these phenotypes. In vivo studies further demonstrated complete tumor regression in MDA-MB-231 xenografts upon PPAP2C knockout. Conclusion This study identifies PPAP2C as a key oncogenic driver and a robust independent prognostic biomarker in breast cancer. The findings provide compelling evidence that PPAP2C represents a promising therapeutic target, offering a new strategic avenue for precision therapy, particularly for aggressive breast cancer subtypes.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.