Evidence map›Paper›PMID 42276991›Full record

ArticleOncogenesis2026

CAF-derived PTGDS drives pancreatic cancer neuroendocrine differentiation and chemoresistance via PAQR9-MAPK.

Jingwen Liang, Wang Peng, Zhou Luan, Luyao Liu, Hai Huang, Haochen Cui, Mengdie Cao, Shiru Chen, Si Xiong, Shuya Bai and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogenesis, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Jingwen LiangDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Wang PengDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Zhou LuanDepartment of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Luyao LiuDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hai HuangDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Haochen CuiDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Mengdie CaoDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Shiru ChenDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Si XiongDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Shuya BaiDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Wei ChenDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Bin ChengDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. b.cheng@tjh.tjmu.edu.cn.
Yuchong ZhaoDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. zhaoyuchongtj@163.com.ORCID http://orcid.org/0000-0003-2245-8541

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The tumor microenvironment, particularly cancer-associated fibroblasts (CAFs), critically influences pancreatic ductal adenocarcinoma (PDAC) progression. Neuroendocrine differentiation (NED) is associated with aggressive tumor behavior and therapy resistance in multiple malignancies, yet its regulation within the PDAC environment is poorly characterized. Through integrated analysis of clinical specimens and transcriptomic datasets, we identified significant enrichment of NED markers correlating with poor patient outcomes. Single-cell RNA sequencing further identified Glycoprotein prostaglandin D2 synthase (PTGDS) as a CAF-derived factor potentially driving NED. Functional studies demonstrated that PTGDS secreted by CAFs robustly induced NED while enhancing proliferation, invasion, migration, and gemcitabine resistance in pancreatic cancer cells. Mechanistically, we established that PTGDS activates MAPK signaling through its membrane receptor PAQR9, and the pharmacological inhibition of MAPK signaling or knockdown of PAQR9 effectively reversed PTGDS-induced malignant phenotypes. These findings reveal a novel CAFs/PTGDS-PAQR9-MAPK signaling axis that promotes NED and drives PDAC progression, offering new therapeutic opportunities to overcome stromal-mediated chemoresistance.

Identifiers

PMID42276991
PMCPMC13482867

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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 OpenQuestion graph.