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

氧化应激和内质网应激相关肝细胞癌预后特征的开发

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作者:Hui Ma, Zhongchen Li, Rongxin Chen, Zhenggang Ren

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.

Conclusion

The OESGs signature showed excellent performance in predicting survival and therapeutic responses for patients with HCC.

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

We demonstrated a positive correlation between oxidative stress and endoplasmic reticulum 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.

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