Yilin Guo

A novel disulfidptosis-related lncRNA signature to predict prognosis and immune response of cervical cancer

Disulfidptosis, a new identified form of regulated cell death, has been implicated in cancer. However, the mechanisms through which disulfidptosis-related long noncoding RNAs (lncRNAs) predict prognosis in cervical cancer (CC) remain unclear. Here, we identified disulfidptosis-related genes and lncRNAs in the cancer genome atlas database. Least absolute shrinkage and selection operator and Cox regression analyses were used to construct a prognostic risk signature based on optimal disulfidptosis-related lncRNAs. The prognostic performance of the signature was evaluated using Kaplan–Meier survival analysis and receiver operating characteristic curves. Correlation between the risk signature, gene mutation landscape, tumor immune microenvironment, and immunotherapy or chemotherapy sensitivity was determined. Additionally, the expression levels of disulfidptosis-related lncRNAs in CC were validated by quantitative PCR. A total of 403 disulfidptosis-related lncRNAs were identified, among which 9 disulfidptosis-related lncRNAs were used to construct a prognostic risk signature that classified patients with CC into high-risk and low-risk groups. Kaplan–Meier, receiver operating characteristic curves, and the concordance index demonstrated that the risk signature exhibited good sensitivity and specificity. The low-risk group exhibited improved survival outcomes and increased sensitivity to immunotherapy, whereas the high-risk group showed heightened sensitivity to to bexarotene, bicalutamide, embelin, FH535, and pazopanib. Quantitative PCR results indicated that ILF3-DT and PPP1R14B-AS1 were downregulated in CC tissues, whereas RUSC1-AS1 was upregulated. In conclusion, we developed a novel prognostic risk signature based on 9 disulfidptosis-related lncRNAs, which may serve as an independent predictor of immunotherapy response and chemotherapy sensitivity in CC.

The significance of m6A RNA methylation modification in prognosis and tumor microenvironment immune infiltration of cervical cancer

Recent studies have highlighted that N6-methyladenosine (m6A) plays a significant role in tumorigenicity and progression. However, the mechanism of m6A modifications in the tumor microenvironment (TME) immune cell infiltration in cervical cancer (CC) remains unclear. Clinical and RNA sequencing data of 25 m6A RNA methylation regulators were acquired from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. LASSO Cox regression analysis was used to generate a prognostic risk signature. m6A modification patterns were identified based on the expression of 25 m6A regulators, and their correlation with TME immune cell-infiltrating characterization was analyzed. Principal component analysis was used to construct an m6A-scoring signature (m6A score) to evaluate the m6A modification patterns of individual CC samples and guide the selection of more effective immunotherapeutic strategies. Genetic and expression alterations of 25 m6A regulators were highly heterogeneous between CC and normal tissues. METTL14 and IGF2BP1 were selected to conduct the prognostic risk signature. Three m6A modification patterns were identified in 659 CC samples, which were associated with distinct clinical outcomes and biological pathways. The TME immune cell-infiltrating characterization of the three m6A modification patterns was highly consistent with 3 tumor immune phenotypes, including immune-excluded, immune-inflamed, and immune-desert phenotypes. Due to the heterogeneity of m6A modification patterns, an m6A scoring signature was established to evaluate the m6A modification patterns of individual CC samples. Univariate and multivariate Cox regression analyses revealed that the m6A score is a robust and independent prognostic biomarker for assessing the prognosis of CC patients. A low m6A score, characterized by higher somatic mutation and higher expression of proliferation-related and DNA repair-related genes, indicated poor overall survival. Activation of immune infiltration was exhibited by the high m6A score, which was likely to have a good response and clinical benefits to antiPD-1/L1 immunotherapy. This study highlights the prognostic value of 25 m6A regulators in CC. The m6A modification is related to immune regulation and the formation of TME heterogeneity and complexity. An m6A scoring signature to clarify the individual m6A modification pattern could enhance our understanding of TME immune cell-infiltrating characterization and guide immunotherapy strategies.