International Journal of General Medicine (May 2022)
Multi-Omics Approaches Identify Necroptosis‑Related Prognostic Signature and Associated Regulatory Axis in Cervical Cancer
Abstract
JuanMei Zhan, Fenfang Yang, Cenhong Ge, Xiaojia Yu Department of Medical Examination Center, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, 310006, People’s Republic of ChinaCorrespondence: Fenfang Yang, Department of Medical Examination Center, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, 310006, People’s Republic of China, Email [email protected]: Cervical cancer is the fourth most frequent malignancy among women globally, with approximately 604,000 new cases and 341,000 deaths per year. Necroptosis is a newly discovered mechanism of cell death involved in biological behaviors of cancer.Methods: LASSO Cox regression analysis was conducted to construct a prognostic necroptosis-related signature. lncRNA–miRNA–mRNA regulatory axis was constructed with a ceRNA network. qRT-PCR was performed to verify our result.Results: A total of 54 necroptosis-related genes were differentially expressed in cervical cancer (all p < 0.05). We also summarized genetic mutation landscape of necroptosis-related genes in cervical cancer. We then developed a necroptosis-related prognostic signature including 13 necroptosis-related genes (ATRX, AXL, DDX58, IDH1, ITPK1, MAP3K7, SLC39A7, TARDBP, TNF, TNFRSF1A, TNFRSF1B, TNFSF10, TRIM11) for cervical cancer. Cervical cancer patients with high riskscore had a poor overall survival (HR = 2.128, p = 0.00194) with an AUC of 0.725, 0.763 and 0.637 in 3-year, 5-year, and 10-year ROC curve. Consensus clustering analysis revealed that all cervical cancer cohort could be divided into three subtypes, which was correlated with different prognosis and immune infiltration (p < 0.05). A PPI network revealed TNF as the hub gene and TNF expression was correlated with immune infiltration (all p < 0.05), microsatellite instability (p < 0.012) and drug sensitivity (p < 0.05). The ceRNA network was performed and identified a lncRNA NUTM2B-AS1/miR-361-5p/TNF regulatory axis for cervical cancer. qRT-PCR result also suggested that TNF was upregulated in cervical cancer (p < 0.001) and associated with a poor overall survival (p = 0.007). Univariate and multivariate analysis demonstrated TNF expression, lymph node metastasis and clinical stage were prognosis factors of cervical cancer patients (p < 0.05).Conclusion: We developed a necroptosis-related prognostic signature including 13 necroptosis-related genes for cervical cancer. Moreover, we also identified a lncRNA NUTM2B-AS1/miR-361-5p/TNF regulatory axis, which may play a vital role in the progression of cervical cancer. Further studies should be conducted to verify these results.Keywords: cervical cancer, necroptosis, prognostic signature, NUTM2B-AS1, miR-361-5p
