Evidence mapPaperPMID 40361374Full record

ReviewCancers2025

Reassessing the Role of Tissue Factor Pathway Inhibitor 2 in Neoplastic and Non-Neoplastic Lesions.

Hiroshi Kobayashi, Hiroshi Shigetomi, Shogo Imanaka

Abstract readReview
In one paragraph

Review in Cancers, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

3 authors.

Hiroshi KobayashiDepartment of Gynecology and Reproductive Medicine, Ms. Clinic MayOne, 871-1 Shijo-cho, Kashihara 634-0813, Japan.ORCID 0000-0002-8124-6269
Hiroshi ShigetomiDepartment of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan.
Shogo ImanakaDepartment of Gynecology and Reproductive Medicine, Ms. Clinic MayOne, 871-1 Shijo-cho, Kashihara 634-0813, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesTissue factor pathway inhibitor 2 (TFPI2) is a serine protease inhibitor that suppresses tumors by preventing extracellular matrix degradation and invasion. In many malignancies, the TFPI2 promoter hypermethylation silences its transcription, increasing tumor aggressiveness. However, TFPI2 paradoxically facilitates tumor progression in certain malignancies. Elevated circulating TFPI2 levels correlate with increased cancer aggressiveness and poor prognosis in ovarian, endometrial, and renal cell carcinoma, though the mechanisms underlying its tumor-promoting effects remain unclear. This review consolidates recent findings on TFPI2 regulation, its downstream targets in cellular homeostasis, and its prognostic significance. Additionally, we reassess TFPI2's role in tumorigenesis, particularly in clear cell carcinoma, as well as in chronic inflammation.

methodsA comprehensive literature search was performed in PubMed and Google Scholar without time restriction.

resultsTFPI2 expression is tightly regulated by transcription factors, signaling molecules, growth factors, cytokines, and epigenetic modification. TFPI2 regulates cell proliferation, inflammation, and extracellular matrix (ECM) remodeling, preserving tissue homeostasis. TFPI2 also regulates vascular endothelial and smooth muscle cell proliferation, key elements of the tumor microenvironment (TME). In the nucleus, it may modulate transcription factors to influence tumor-associated macrophage (TAM) polarization, facilitating cancer invasion. Its expression may be shaped by interactions between cancer cells and TAM activation. Beyond tumorigenesis, TFPI2 contributes to both inflammatory progression and resolution in diabetes, atherosclerosis, and preeclampsia.

conclusionsTFPI2 may interact with TAMs and inflammatory cells to regulate cell proliferation and inflammation, maintaining tissue homeostasis.

Indexed as

clear cell carcinomaovarian cancertissue factor pathway inhibitor 2tumor promotertumor suppressor

Identifiers

PMID40361374
PMCPMC12071115

What Socratic holds

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Registered trials

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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 Socratic graph.