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.

Objective: The present study aimed to investigate the therapeutic mechanism of Hedyotis diffusa Willd (HDW) and Scutellaria barbata (SB) in ccRCC using a combination of single-cell RNA sequencing (scRNA-seq) and network pharmacology. Methods: The active ingredients and potential molecular targets of HDW-SB were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Gene expression data (GSE53757) were obtained from the Gene Expression Omnibus database. The hub genes of HDW-SB against ccRCC were identified via the protein–protein interaction network, and further analyzed by molecular complex detection. The roles of these genes in the diagnosis and immune infiltration of ccRCC were analyzed. The clinical significance of hub genes was verified using scRNA-seq data (GSE121638) and molecular docking. Results: Following the PPI network analysis, 29 hub genes of HDW-SB against ccRCC were identified. All hub genes, except for CENPE, had significantly different expressions in tumor tissue and a more accurate diagnosis of ccRCC. Fifteen cell clusters were defined based on the scRNA-seq dataset, and the clusters were annotated as six cell types using marker genes. TYMS and KIAA0101 from hub genes were highly expressed in NK cells. Three active compounds, quercetin, luteolin, and baicalein, were found to target TYMS and KIAA0101 from the compound-target interaction network. Conclusion: 29 hub genes of HDW-SB against ccRCC were identified and showed good performance in terms of diagnosis and prognosis. Moreover, among these hub genes docking with the main ingredients of HDW-SB, TYMS and KIAA0101 exerted anti-ccRCC effects through NK cells.

Rationale: Endometrial carcinoma (EC) is a frequently occurring cancer in the female reproductive system. Nevertheless, the occurrence of cardiac metastasis in cases of EC is uncommon and represents a significant risk to women’s health. Patient concerns: A 58-year-old female patient experienced abnormal vaginal bleeding for over 8 months and was eventually diagnosed with stage IVC (FIGO 2023) endometrial cancer characterized by mismatch repair deficiency that had spread to the heart. Diagnoses: Stage IVC (FIGO 2023) mismatch repair deficiency EC with cardiac metastasis. Interventions: After a thorough discussion with the multidisciplinary team, a detailed noninvasive treatment strategy was established: the initial phase involved 6 cycles of induction therapy using a combination of paclitaxel and carboplatin along with tislelizumab, resulting in a partial response. This was followed by 3 cycles of maintenance therapy with tislelizumab as a standalone treatment. Outcomes: Following the maintenance treatment, the cardiac metastasis was entirely eliminated. The patient experienced a progression-free survival duration of 9 months. Lessons: For patients with EC who have metastasized to rare sites such as the heart, comprehensive management guided by multidisciplinary team consultation is crucial, as it can significantly prolong survival.

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.