Development of Novel PANoptosis-Related Gene Signatures to Predict the Prognosis of Patients With Stomach Adenocarcinoma – Research

Background:

PANoptosis, as an inflammatory programmed cell death, is involved in tumor development. This study set out to discover novel PANoptosis-correlated prognostic signatures in stomach adenocarcinoma (STAD), a prevalent malignancy of the digestive system.

Methods:

STAD samples were derived from a public database, and PANoptosis-related genes (PRGs) were acquired from existing reports. Prognosis-related PRGs were screened by univariate Cox regression analysis. Molecular subtypes of STAD were identified by the “ConsensusClusterPlus” package. The “Limma” package was employed to filter differentially expressed genes (DEGs) between different subtypes. PANoptosis-related prognostic signatures in STAD were identified to establish the RiskScore model. The RiskScore and some of the clinical features were integrated to establish a nomogram. Immune cell infiltration and TIDE score in different risk groups were compared. Correlation between immune checkpoint genes, drug sensitivity, and RiskScore was analyzed by the Spearman method. The biological function of PANoptosis-related signature genes in STAD was preliminarily explored by in vitro cell experiments.

Results:

Based on 18 prognosis-related PRGs, two molecular subtypes of STAD were recognized, and the C1 subtype showed a lower overall survival (OS) rate than the C2 subtype. Further, three PANoptosis-related signature genes (APOD, GPC3, and SERPINE1) were determined to establish a RiskScore model that could accurately assess the prognostic outcomes for STAD patients. Then, by integrating RiskScore with clinical features, a nomogram was established. The high-risk group had higher immune cell infiltration and TIDE score and lower OS rate than those with a low risk. RiskScore was positively correlated with nine immune checkpoint genes. Besides, we screened 23 drugs that significantly correlated with RiskScore. In vitro cell experiments showed that the mRNA and protein levels of APOD, GPC3, and SERPINE1 were upregulated in the STAD cell line and that APOD knockout significantly reduced cancer cell proliferation, migration, and invasion levels and increased the apoptotic capacity of the STAD cell line.

Conclusion:

This study established a PANoptosis-related RiskScore model for assessing STAD patient prognosis, which could contribute to the personalized treatment of STAD.