Identification of the role of endoplasmic reticulum stress genes in endometrial cancer and their association with tumor immunity.
Bioinformatic analysis
Endometrial cancer
Endoplasmic reticulum stress
Immune infiltration
Prognosis
Risk signature
Journal
BMC medical genomics
ISSN: 1755-8794
Titre abrégé: BMC Med Genomics
Pays: England
ID NLM: 101319628
Informations de publication
Date de publication:
25 10 2023
25 10 2023
Historique:
received:
17
04
2023
accepted:
30
09
2023
medline:
27
10
2023
pubmed:
26
10
2023
entrez:
25
10
2023
Statut:
epublish
Résumé
Endometrial cancer (EC) is one of the worldwide gynecological malignancies. Endoplasmic reticulum (ER) stress is the cellular homeostasis disturbance that participates in cancer progression. However, the mechanisms of ER Stress on EC have not been fully elucidated. The ER Stress-related genes were obtained from Gene Set Enrichment Analysis (GSEA) and GeneCards, and the RNA-seq and clinical data were downloaded from The Cancer Genome Atlas (TCGA). The risk signature was constructed by the Cox regression and the least absolute shrinkage and selection operator (LASSO) analysis. The significance of the risk signature and clinical factors were tested by time-dependent receiver operating characteristic (ROC) curves, and the selected were to build a nomogram. The immunity correlation was particularly analyzed, including the related immune cells, pathways, and immune checkpoints. Functional enrichment, potential chemotherapies, and in vitro validation were also conducted. An ER Stress-based risk signature, consisting of TRIB3, CREB3L3, XBP1, and PPP1R15A was established. Patients were randomly divided into training and testing groups with 1:1 ratio for subsequent calculation and validation. Based on risk scores, high- and low-risk subgroups were classified, and low-risk subgroup demonstrated better prognosis. The Area Under Curve (AUC) demonstrated a reliable predictive capability of the risk signature. The majority of significantly different immune cells and pathways were enriched more in low-risk subgroup. Similarly, several typical immune checkpoints, expressed higher in low-risk subgroup. Patients of the two subgroups responded differently to chemotherapies. We established an ER Stress-based risk signature that could effectively predict EC patients' prognosis and their immune correlation.
Sections du résumé
BACKGROUND
Endometrial cancer (EC) is one of the worldwide gynecological malignancies. Endoplasmic reticulum (ER) stress is the cellular homeostasis disturbance that participates in cancer progression. However, the mechanisms of ER Stress on EC have not been fully elucidated.
METHOD
The ER Stress-related genes were obtained from Gene Set Enrichment Analysis (GSEA) and GeneCards, and the RNA-seq and clinical data were downloaded from The Cancer Genome Atlas (TCGA). The risk signature was constructed by the Cox regression and the least absolute shrinkage and selection operator (LASSO) analysis. The significance of the risk signature and clinical factors were tested by time-dependent receiver operating characteristic (ROC) curves, and the selected were to build a nomogram. The immunity correlation was particularly analyzed, including the related immune cells, pathways, and immune checkpoints. Functional enrichment, potential chemotherapies, and in vitro validation were also conducted.
RESULT
An ER Stress-based risk signature, consisting of TRIB3, CREB3L3, XBP1, and PPP1R15A was established. Patients were randomly divided into training and testing groups with 1:1 ratio for subsequent calculation and validation. Based on risk scores, high- and low-risk subgroups were classified, and low-risk subgroup demonstrated better prognosis. The Area Under Curve (AUC) demonstrated a reliable predictive capability of the risk signature. The majority of significantly different immune cells and pathways were enriched more in low-risk subgroup. Similarly, several typical immune checkpoints, expressed higher in low-risk subgroup. Patients of the two subgroups responded differently to chemotherapies.
CONCLUSION
We established an ER Stress-based risk signature that could effectively predict EC patients' prognosis and their immune correlation.
Identifiants
pubmed: 37880674
doi: 10.1186/s12920-023-01679-5
pii: 10.1186/s12920-023-01679-5
pmc: PMC10599039
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
261Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
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