Multi-Omics Approaches Identify Necroptosis‑Related Prognostic Signature and Associated Regulatory Axis in Cervical Cancer

Abstract

Background 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.

A novel necroptosis-related LncRNA signature for prediction of prognosis and therapeutic responses of head and neck squamous cell carcinoma

“…Therefore, the development of biomarkers that can predict the prognosis and treatment benefit of HNSCC patients is necessary. With the advancement of high-throughput sequencing technology and the development of bioinformatics, researchers have more deeply decoded HNSCC and derived a large number of biomarkers ( Zhan et al, 2022 ; Zhang et al, 2022 ). These biomarkers covered a wide range of biological functions, including inflammation, pyroptosis, immunity, and hypoxia et al ( Han et al, 2022 ; Li et al, 2022 ; Lu and Jia, 2022 ; Zhu et al, 2022 ).…”

“…Recently, the researchers found that necroptosis inhibited tumor progression and metastasis by regulating programmed tumor cell death in various solid tumors ( Beretta and Zaffaroni, 2022 ). Necroptosis has been used as a novel biomarker to guide the treatment of cancer patients in clinical practice ( Chen et al, 2022 ; Luo et al, 2022 ; Zhan et al, 2022 ). For example, Luo et al have precisely predicted the prognosis and treatment benefit of colorectal cancer patients by developing necrosis-related molecular characteristics ( Chen et al, 2022 ).…”

Omics approaches to better understand the molecular mechanism of necroptosis and their translational implications

“…GLUD1 and PYGL have been shown to be activated downstream of RIPK3 in necroptosis. 98 Other groups have also used similar transcriptomics and bioinformatic approaches to establish a necroptosis-related prognostic model in different types of cancers, such as cervical cancer, 99 renal carcinoma, 100 pancreatic adenocarcinoma 101 and other cancers where regulation of necroptosis-related genes affects tumorigenesis. 102 In addition to cancer, a transcriptomic and metabolic profiling study showed the involvement of necroptosis in chronic obstructive pulmonary disease (COPD).…”

Fabrication of magnetic nanocomposite as responsive drug delivery vehicle for cervical cancer therapy

“…The most prevalent cancer among women worldwide is cervical cancer, and according to statistics, approximately 527,624 new cases of cervical cancer are diagnosed each year 1–3 . Chemotherapy is currently the primary treatment for cervical cancer.…”