Open AccessIdentifying cancer cell‐secreted proteins that activate cancer‐associated fibroblasts as prognostic factors for patients with pancreatic cancer
Author(s) -
Luo Qiankun,
Liu Jiayin,
Fu Qiang,
Zhang Xu,
Yu Pengfei,
Liu Pan,
Zhang Jiali,
Tian Huiyuan,
Chen Song,
Zhang Hongwei,
Qin Tao
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17596
Subject(s) - pancreatic cancer , cancer cell , metastasis , cancer , receiver operating characteristic , medicine , cancer research , gene expression profiling , western blot , gene expression , gene , biology , bioinformatics , oncology , pathology , biochemistry
The study aimed to investigate the mechanism by which cancer‐associated fibroblasts (CAFs) are activated by cancer cells and construct a risk model to predict the prognosis of patients with pancreatic cancer (PC) after surgery. Pancreatic stellate cells were isolated from human pancreatic tissue and co‐cultured with cancer cells to verify their crosstalk. Liquid chromatography–tandem mass spectrometry was used to detect proteins secreted by cancer cells. The online tools Gene Expression Profiling Interactive Analysis, UALCAN, and the Human Protein Atlas were used to analyse gene expression in PC. Expression data from the cancer genome atlas and the clinical samples were used to develop a training receiver operating characteristic (ROC) model and an external validation ROC model, respectively. We identified that cancer cells promote the activation of inflammatory CAFs (iCAF) through secretory proteins, which promote PC metastasis. Six candidate proteins secreted by cancer cells were identified which promote iCAF formation. These proteins were highly expressed in tumours and were associated with a poor prognosis in patients with PC. Moreover, a 6‐gene model was constructed to predict death risk in patients at 1, 2 and 3 years after surgery. The training areas under the ROC curves (AUC) of 1‐, 2‐ and 3‐year death risks were 0.780, 0.792 and 0. 825, respectively. The externally validated AUC of death at 3 years post‐surgery was 0.728. In conclusion, cancer cell‐secreted proteins play a vital role in iCAF formation, and the 6‐gene model may be a potential marker for predicting whether PC patients will benefit from surgery.