Identification of a prognostic model based on immune and hypoxia-related gene expressions in cervical cancer

J Obstet Gynaecol. 2023 Dec;43(2):2277242. doi: 10.1080/01443615.2023.2277242. Epub 2023 Nov 8.

Abstract

Background: Tumour immune microenvironment (TIME) has long been a key direction of tumour research. Understanding the occurrence, metastasis and other processes of cervical cancer (CC) is of great significance in the diagnosis and prognosis of tumours.

Methods: Here, this study applied the univariate Cox regression model to determine the prognostic association of immune and hypoxia signature genes in CC, and used Least Absolute Shrinkage and Selection Operator (LASSO) Cox method to build immune and hypoxia related risk score model to uncover the immune signature of the TIME of CC. Moreover, we used in vitro experiment to validate the expression level of signature genes. Notably, we assessed the predictive effect of anti-PD1/PDL1 immunotherapy using risk score model.

Results: Through the LASSO Cox regression model, we obtained 12 characteristic genes associated with the prognosis of CC, and also associated with immunity and hypoxia. Interestingly, the high-risk group had the properties of high hypoxia and low immunity, while the low-risk group had the properties of low hypoxia and high immunity. In the low-risk group, patients lived longer and had a significant therapeutic advantage of anti-PD-1 immunotherapy.

Conclusions: Established risk scores model can help predict response to anti-PD-1 immunotherapy of CC.

Keywords: Cervical cancer; hypoxia; immune; risk score model; tumour immune microenvironment.

Plain language summary

The survival rate of cervical cancer (CC) is still low. A prognostic model for CC is urgently needed to improve the prognosis and survival. This study constructed a risk scoring models based on 12 characteristic gene related to hypoxia and immunity, including CX3CL1, CXCL3, GHSR, DLL4, FGFR2, PDF, KLRK1, MAP3K14, RETNLB, PRDX2, P4HA1 and PGK1, which can help predict the prognosis of PD-1 immunotherapy in CC patients. The high-risk group may have the properties of high hypoxia and low immunity, while the low-risk group patients live longer and have obvious therapeutic advantages in anti-PD-1 immunotherapy. Our findings suggest a potential link between hypoxia, immunity, prognosis, tumour immune microenvironment and response to immunotherapy in CC patients.

MeSH terms

  • Female
  • Fetal Hypoxia
  • Gene Expression
  • Humans
  • Hypoxia / genetics
  • Prognosis
  • Tumor Microenvironment / genetics
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / therapy