Construction of a Six-Gene Prognostic Risk Model Related to Hypoxia and Angiogenesis for Cervical Cancer

Abstract

Background: The prognosis of cervical cancer (CC) is poor and not accurately reflected by the primary tumor node metastasis staging system. Our study aimed to develop a novel survival-prediction model.Methods: Hallmarks of CC were quantified using single-sample gene set enrichment analysis and univariate Cox proportional hazards analysis. We linked gene expression, hypoxia, and angiogenesis using weighted gene co-expression network analysis (WGCNA). Univariate and multivariate Cox regression was combined with the random forest algorithm to construct a prognostic model. We further evaluated the survival predictive power of the gene signature using Kaplan-Meier analysis and receiver operating characteristic (ROC) curves.Results: Hypoxia and angiogenesis were the leading risk factors contributing to poor overall survival (OS) of patients with CC. We identified 109 candidate genes using WGCNA and univariate Cox regression. Our established prognostic model contained six genes (MOCSI, PPP1R14A, ESM1, DES, ITGA5, and SERPINF1). Kaplan-Meier analysis indicated that high-risk patients had worse OS (hazard ratio = 4.63, p < 0.001). Our model had high predictive power according to the ROC curve. The C-index indicated that the risk score was a better predictor of survival than other clinicopathological variables. Additionally, univariate and multivariate Cox regressions indicated that the risk score was the only independent risk factor for poor OS. The risk score was also an independent predictor in the validation set (GSE52903). Bivariate survival prediction suggested that patients exhibited poor prognosis if they had high z-scores for hypoxia or angiogenesis and high risk scores.Conclusions: We established a six-gene survival prediction model associated with hypoxia and angiogenesis. This novel model accurately predicts survival and also provides potential therapeutic targets.

Oncogenic HPV-induced high expression of ESM1 predicts poor prognosis and regulates aerobic glycolysis in cervical cancer

“… 11 A survival prediction model was constructed in the context of cervical cancer by integrating ESM1 and five additional genes that are linked to hypoxia and angiogenesis. 12 The overexpression of ESM1 has been found to facilitate carcinoma angiogenesis and the progression of cervical cancer via the VEGF/ERK signaling pathway. 13 Despite the carcinogenic role of ESM1 in cervical cancer is emerging, a comprehensive understanding of its involvement and regulatory mechanism in the initiation and progression of cervical cancer, as well as its correlation with HPV infection, has not been fully elucidated.…”

Sequencing-based transcriptome analysis reveals diversification of immune response- and angiogenesis-related expression patterns of early-stage cervical carcinoma as compared with high-grade CIN

“…Another challenging issue is the role of inflammation, a recognized promoter of oncogenesis and immune suppression ( 16 , 17 ); at the same time, however, bioinformatics research on TCGA cases of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC-TCGA) has evidenced that higher patients’ survival rates correlated with higher immune scores ( 15 ). Recent studies also suggest that angiogenesis signature genes can help in stratifying CeCa molecular phenotypes and that there is a tight association between the angiogenic and immune expression profiles ( 18 , 19 ).…”

Efeito de nanovesículas extracelulares derivadas de linhagens tumorais de linfoma T cutâneo em queratinócitos imortalizados

“…Observamos que o tratamento com sEV-LCCT alterou significativamente a expressão de ESM1, sendo um dos seis genes com maior regulação positiva nos queratinócitos tratados com sEV-LCCT por 4h. A expressão de ESM1 é fator de mau prognostico em leucemia mieloide aguda (AML)(Chen et al 2022) e outros cânceres(Liu et al 2022, Huang et al 2021, Wang, Li and Li 2021. Nossos resultados sugerem que sEV tumorais podem estar relacionadas com a alta expressão de fatores angiogênicos observados nos pacientes com LCCT e indicam que as células tumorais LCCT modulam células do epitélio para criar um ambiente pró-oncogênico.…”