Development of a Combined Oxidative Stress and Endoplasmic Reticulum Stress-Related Prognostic Signature for Hepatocellular Carcinoma.

Hepatocellular carcinoma endoplasmic reticulum stress oxidative stress prognosis.

Journal

Combinatorial chemistry & high throughput screening
ISSN: 1875-5402
Titre abrégé: Comb Chem High Throughput Screen
Pays: United Arab Emirates
ID NLM: 9810948

Informations de publication

Date de publication:
10 Nov 2023
Historique:
received: 04 05 2023
revised: 17 09 2023
accepted: 04 10 2023
medline: 14 11 2023
pubmed: 14 11 2023
entrez: 14 11 2023
Statut: aheadofprint

Résumé

Oxidative stress and endoplasmic reticulum stress are important components of the cellular stress process, which plays a critical role in tumor initiation and progression. First, the correlation between oxidative stress and endoplasmic reticulum stress was detected in 68 human hepatocellular carcinoma (HCC) tissue microarray samples by immunohistochemistry. Differentially expressed oxidative stress- and endoplasmic reticulum stressrelated genes (OESGs) then were screened in HCC. Next, an OESGs prognostic signature was constructed for HCC in the training cohort (TCGA-LIHC from The Cancer Genome Atlas), by least absolute shrinkage and selection operator Cox and stepwise Cox regression analyses, and was verified in the external cohort (GSE14520 from the Gene Expression Omnibus). The MCP counter was employed to evaluate immune cell infiltration. The C-index was used to evaluate the predictive power of prognostic signature. Finally, a prognostic nomogram model was constructed to predict the survival probability of patients with HCC based on the results of Cox regression analysis. We demonstrated a positive correlation between oxidative stress and ER stress in human HCC samples. We then identified five OESGs as a prognostic signature consisting of IL18RAP, ECT2, PPARGC1A, STC2, and NQO1 for HCC. Related risk scores correlated with tumor stage, grade, and response to transcatheter arterial chemoembolization therapy, and the higher risk score group had less T cells, CD8+ T cells, cytotoxic lymphocytes and natural killer cell infiltration. The C-index of our OESGs prognostic signature was superior to four previously published signatures. Furthermore, we developed a nomogram based on the OESGs prognostic signature and clinical parameters for patients with HCC that is an effective quantitative analysis tool to predict patient survival. The OESGs signature showed excellent performance in predicting survival and therapeutic responses for patients with HCC.

Sections du résumé

BACKGROUND BACKGROUND
Oxidative stress and endoplasmic reticulum stress are important components of the cellular stress process, which plays a critical role in tumor initiation and progression.
METHODS METHODS
First, the correlation between oxidative stress and endoplasmic reticulum stress was detected in 68 human hepatocellular carcinoma (HCC) tissue microarray samples by immunohistochemistry. Differentially expressed oxidative stress- and endoplasmic reticulum stressrelated genes (OESGs) then were screened in HCC. Next, an OESGs prognostic signature was constructed for HCC in the training cohort (TCGA-LIHC from The Cancer Genome Atlas), by least absolute shrinkage and selection operator Cox and stepwise Cox regression analyses, and was verified in the external cohort (GSE14520 from the Gene Expression Omnibus). The MCP counter was employed to evaluate immune cell infiltration. The C-index was used to evaluate the predictive power of prognostic signature. Finally, a prognostic nomogram model was constructed to predict the survival probability of patients with HCC based on the results of Cox regression analysis.
RESULTS RESULTS
We demonstrated a positive correlation between oxidative stress and ER stress in human HCC samples. We then identified five OESGs as a prognostic signature consisting of IL18RAP, ECT2, PPARGC1A, STC2, and NQO1 for HCC. Related risk scores correlated with tumor stage, grade, and response to transcatheter arterial chemoembolization therapy, and the higher risk score group had less T cells, CD8+ T cells, cytotoxic lymphocytes and natural killer cell infiltration. The C-index of our OESGs prognostic signature was superior to four previously published signatures. Furthermore, we developed a nomogram based on the OESGs prognostic signature and clinical parameters for patients with HCC that is an effective quantitative analysis tool to predict patient survival.
CONCLUSION CONCLUSIONS
The OESGs signature showed excellent performance in predicting survival and therapeutic responses for patients with HCC.

Identifiants

pubmed: 37957902
pii: CCHTS-EPUB-136075
doi: 10.2174/0113862073257308231026073951
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Auteurs

Hui Ma (H)

Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA.

Zhongchen Li (Z)

Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.

Rongxin Chen (R)

Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.

Zhenggang Ren (Z)

Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.

Classifications MeSH