Evidence map›Paper›PMID 40727473›Full record

ArticleFrontiers in oncology2025

Elevated plasma levels of WAP four-disulfide core domain 2 as a potential prognostic biomarker for various cancers.

Makoto Watanabe, Katsuaki Ieguchi, Nobuyuki Onishi, Takashi Shimizu, Ryotaro Ohkuma, Risako Suzuki, Emiko Mura, Nana Iriguchi, Tomoyuki Ishiguro, Yuya Hirasawa and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Makoto WatanabeDepartment of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa Medical University, Tokyo, Japan.
Katsuaki IeguchiDepartment of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa Medical University, Tokyo, Japan.
Nobuyuki OnishiDepartment of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa Medical University, Tokyo, Japan.
Takashi ShimizuDepartment of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa Medical University, Tokyo, Japan.
Ryotaro OhkumaDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa Medical University, Tokyo, Japan.
Risako SuzukiDepartment of Pharmacology, School of Medicine, Showa Medical University, Tokyo, Japan.
Emiko MuraDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa Medical University, Tokyo, Japan.
Nana IriguchiDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa Medical University, Tokyo, Japan.
Tomoyuki IshiguroDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa Medical University, Tokyo, Japan.
Yuya HirasawaDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa Medical University, Tokyo, Japan.
Go IkedaDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa Medical University, Tokyo, Japan.
Masahiro ShimokawaDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa Medical University, Tokyo, Japan.
Hirotsugu AriizumiDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa Medical University, Tokyo, Japan.
Atsushi HoriikeDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa Medical University, Tokyo, Japan.
Kiyoshi YoshimuraClinical Research Institute for Clinical Pharmacology and Therapeutics, Showa Medical University, Tokyo, Japan.
Takuya TsunodaDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa Medical University, Tokyo, Japan.
Mayumi TsujiPharmacological Research Center, Showa Medical University, Tokyo, Japan.
Shinichi KobayashiClinical Research Institute for Clinical Pharmacology and Therapeutics, Showa Medical University, Tokyo, Japan.
Yuji KiuchiDepartment of Pharmacology, School of Medicine, Showa Medical University, Tokyo, Japan.
Satoshi WadaDepartment of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa Medical University, Tokyo, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Although WAP four-disulfide core domain 2 (WFDC2) is widely recognized as a diagnostic biomarker for ovarian cancer, its function in other cancer types remains unclear. The aim of this study was to evaluate the prognostic potential of WFDC2 across multiple cancers. Methods: Publicly available transcriptomic datasets were analyzed to compare WFDC2 mRNA expression in normal and tumor tissues across various cancer types. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to assess the association between WFDC2 mRNA expression and overall survival (OS). Plasma WFDC2 levels were measured using enzyme-linked immunosorbent assay in healthy donors as well as patients with gastric, lung, colorectal, esophageal, and pancreatic cancers. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of WFDC2. Kaplan-Meier analysis was conducted to evaluate the association between WFDC2 expression and OS. Cox proportional hazards regression analysis was performed to assess the prognostic significance of WFDC2 expression. Results: WFDC2 mRNA expression was significantly elevated in gastric cancer, lung adenocarcinoma (LUAD), esophageal carcinoma, and pancreatic ductal adenocarcinoma (p < 0.01); however, it was significantly lower in colorectal cancer (p < 0.005). Kaplan-Meier analysis indicated that elevated WFDC2 mRNA expression in LUAD was only significantly associated with prolonged OS (p = 0.017), whereas no significant associations were observed in other cancer types. Moreover, plasma WFDC2 levels were significantly higher in all cancer patient groups than in healthy donors (p < 0.0001). ROC analysis revealed potential diagnostic performance, with an area under the curve of 0.890 (95% CI: 0.844-0.936) for distinguishing patients with cancer from healthy donors. Subgroup analysis indicated diagnostic performance across all cancer types. Elevated plasma WFDC2 levels were significantly associated with shorter OS in esophageal cancer (p = 0.0226). Multivariate Cox regression analysis confirmed that plasma WFDC2 concentration was an independent prognostic factor in gastric (HR = 1.04, 95% CI: 1.00-1.07, p = 0.019) and esophageal cancers (HR = 1.08, 95% CI: 1.02-1.13, p = 0.006). Conclusion: Plasma WFDC2 levels demonstrated potential diagnostic performance across multiple cancers and were significantly associated with poor prognosis in gastric and esophageal cancers.

Indexed as

biomarkercancer prognosisELISAplasmaWFDC2

Identifiers

PMID40727473
PMCPMC12301208

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.