Elucidating the pathway activity and prognostic significance of diverse
regulatory cell death patterns in pancreatic cancer
- Jiazheng Sun,
- Yulan Zeng
Jiazheng Sun
Liyuan Hospital of Tongji Medical College of Huazhong University of Science and Technology
Author ProfileYulan Zeng
Liyuan Hospital of Tongji Medical College of Huazhong University of Science and Technology Department of Respiratory and Critical Care Medicine
Corresponding Author:[email protected]
Author ProfileAbstract
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Pancreatic cancer (PACA) remains the most aggressive tumor, with no
observed improvement in prognosis over the last decade. The current TNM
staging system, which is based on anatomic structure, is not effective
in precisely identifying patients who would respond well to treatment.
Therefore, there is an urgent need for suitable biomarkers in precision
medicine. Regulated cell death (RCD) is a controlled mechanism directed
by genes that eliminate infected, damaged, or sick cells. It is unclear,
however, how exactly the majority of RCD patterns regulate the
microenvironment of PACA. The study utilized a range of bioinformatics
techniques to investigate the involvement of diverse types of RCD
patterns in PACA. The aim was to gain fresh perspectives on the
prognosis and treatment of PACA. The study conducted a screening of
RCD-related genes using consensus cluster analysis, the weighted gene
co-expression network analysis (WGCNA), and univariate Cox regression
based on the expression files of 1576 PACA patients from 12 multicenter
cohorts. Furthermore, the study developed the RCDS signature utilizing
101 machine-learning algorithms, which consisted of six genes (UNC13D,
GAPDH, VEGFA, ANGPTL4, CREB3L1, and NT5E). The performance of RCDS
signature in predicting the prognosis of PACA patients was superior to
those of clinical features such as grade, stage, and age. Additionally,
the RCDS signature has a guiding influence on immunotherapy based on the
characteristics of the immunological score, immune cell infiltration
level, and immunotherapy markers.