Necroptosis-related gene to construct a signature to predict the prognosis and immune features in patients with cervical cancer

Cervical cancer (CC) is the fourth most deadly disease in women. Necroptosis is a programmed form of necrosis. Increasing evidences indicated that abnormal expression of necroptosis-related genes was associated with prognosis in cancers. However, the value of necroptosis-related genes (NRGs) as potential prognostic biomarker for CC is still unclear. The expression matrix and clinicopathological information were achieved from the The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) datasets. Consensus clustering classification was performed and its correlation with prognosis, clinicopathological features and immunity was analyzed. Subsequently, we constructed a risk signature (NRGscore) by least absolute shrinkage and selection operator (LASSO) regression analysis. CIBERSORT, single sample geneset enrichment analysis (ssGSEA) and ESTIMATE were used to explore the difference in immune landscape in patients with different risks. We also evaluated the NRGscore signature in immunotherapy and chemotherapy response prediction between high- and low-risk groups. Quantitative reverse transcription PCR (qRT-PCR) was performed to validate the expression difference of key genes in CC tissues. We constructed the prognostic signature with 9 necroptosis-related genes and patients with high-risk score featured with significantly worse prognosis, lower proportion of immune cell infiltration, and higher proportion of immunosuppressive cells. Multivariate regression analyses displayed that NRGscore signature could not only independently predicted the overall survival but also performed better than any other clinical and pathological factors. The qRT-PCR results demonstrated most of NRGs were differently expressed in CC samples. The NRGscore signature effectively predicted the prognosis of CC patients and demonstrated close relationship with the tumor immune microenvironment, chemotherapy and immunotherapy responses. These NRGs could provide potential targets with regard to the immunotherapy for individualized treatment.

Cervical cancer; Chemotherapy; Necroptosis; Immunotherapy; Prognosis

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