ArticlePloS one2014
Gross cystic disease fluid protein-15/prolactin-inducible protein as a biomarker for keratoconus disease.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 61 citations in OpenAlex.
- The candidate proteins associated with keratoconus: A meta-analysis and bioinformatic analysis.PloS one · 2024Pooled it
- Systematically Displaying the Pathogenesis of KeratoconusFrontiers in medicine · 2021Pooled it
- Review
- Oxidative Stress in Keratoconus Is Evident in Tear Fluid and Stromal Cells and Alleviated in Cell Culture by Sulforaphane.Investigative ophthalmology & visual science · 2026Article
- Sex Hormones and Keratoconus: In Search of the Link.Journal of clinical medicine · 2026Article
- Oxidative-stress related increase in keratoconus tear MDA and GPX3 while NRF2-antioxidant functions decrease in stromal cells.bioRxiv : the preprint server for biology · 2025Article
- Investigating prolactin-induced protein and its role in modulating the metabolic state of the keratoconus microenvironment.Experimental eye research · 2025Review
- The Impact of Sex Hormones on Keratoconus.Journal of clinical medicine · 2025Review
- Article
- Effects of hypoxia in the diabetic corneal stroma microenvironment.Experimental eye research · 2024Article
- Animal Models for the Study of Keratoconus.Cells · 2023Review
- Review
- Collagen Crosslinking for Keratoconus: Cellular Signaling Mechanisms.Biomolecules · 2023Article
- Revealing the presence of tear extracellular vesicles in Keratoconus.Experimental eye research · 2022Article
- Tear proteomics analysis of patient suffered from delayed mustard gas keratopathy.Proteome science · 2022Article
- Pathogenesis of keratoconus: NRF2-antioxidant, extracellular matrix and cellular dysfunctions.Experimental eye research · 2022Review
- Insights into the Antibacterial Activity of Prolactin-Inducible Protein against the Standard and Environmental MDR Bacterial Strains.Microorganisms · 2022Article
- A Review of Emerging Tear Proteomics Research on the Ocular Surface in Ocular Allergy.Biology · 2022Review
- Comprehensive Transcriptome Analysis of Patients With Keratoconus Highlights the Regulation of Immune Responses and Inflammatory Processes.Frontiers in genetics · 2022Article
- Prolactin Inducible Protein, but Not Prolactin, Is Present in Human Tears, Is Involved in Tear Film Quality, and Influences Evaporative Dry Eye Disease.Frontiers in medicine · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Keratoconus (KC) is a bilateral degenerative disease of the cornea characterized by corneal bulging, stromal thinning, and scarring. The etiology of the disease is unknown. In this study, we identified a new biomarker for KC that is present in vivo and in vitro. In vivo, tear samples were collected from age-matched controls with no eye disease (n = 36) and KC diagnosed subjects (n = 17). Samples were processed for proteomics using LC-MS/MS. In vitro, cells were isolated from controls (Human Corneal Fibroblasts-HCF) and KC subjects (Human Keratoconus Cells-HKC) and stimulated with a Vitamin C (VitC) derivative for 4 weeks, and with one of the three transforming growth factor-beta (TGF-β) isoforms. Samples were analyzed using real-time PCR and Western Blots. By using proteomics analysis, the Gross cystic disease fluid protein-15 (GCDFP-15) or prolactin-inducible protein (PIP) was found to be the best independent biomarker able to discriminate between KC and controls. The intensity of GCDFP-15/PIP was significantly higher in healthy subjects compared to KC-diagnosed. Similar findings were seen in vitro, using a 3D culture model. All three TGF-β isoforms significantly down-regulated the expression of GCDFP-15/PIP. Zinc-alpha-2-glycoprotein (AZGP1), a protein that binds to PIP, was identified by proteomics and cell culture to be highly regulated. In this study by different complementary techniques we confirmed the potential role of GCDFP-15/PIP as a novel biomarker for KC disease. It is likely that exploring the GCDFP-15/PIP-AZGP1 interactions will help better understand the mechanism of KC disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.