Identification of m6A-Associated Gene DST as a Prognostic and Immune-Associated Biomarker in Breast Cancer Patients.

BACKGROUND: N6-methyladenosine (m6A) is most common internal RNA modification in eukaryotic cells. Existing evidence shows that m6A is closely related to pathogenesis and progression in breast cancer (BRCA). Therefore, it is critical to investigate the key role of m6A target genes in BRCA. METHODS: M6A target genes in BRCA are acquired using RMVar online database. The differentially expressed genes (DEGs) from three microarray datasets (GSE5764, GSE22358, GSE9014) is processed by GEO2R. Oncomine, GEPIA, UALCAN and TNMplot were applied to validate the expression of DST. Survival analyses were performed via DRUGSURV and Kaplan-Meier Plotter database. Univariable survival and multivariate Cox analysis were completed to assess the prognostic value of DST and receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic value of DST. We also investigated the correlation between DST and cancer immune infiltration via using CIBERSORT, TIMER and TISIDB. RESULTS: DST and COL11A1 were significantly expressed in both DEGs and m6A target genes set. COL11A1 show no significance on the patients' survival. However, high expression of DST was related to the favorable prognosis. Multivariate analysis revealed that the DST dysregulation is an independent prognostic factor and ROC indicated that the great diagnostic value of DST with AUC of 0.948. Subsequently, immunological analyses showed that DST was significantly associated with various immune infiltration cells, including NK cells, T helper cells and Mast cells. Furthermore, DST was also related with multiple immune checkpoints and chemokines, including LAG3, LMTK3 CD24, CXCL12, KDR and CX3CR1. These results indicated the potential roles of DST in the development of BRCA via altering the immune response. CONCLUSION: DST can influence the development and progression of BRCA by altering the immune microenvironment.

Development and validation of a prognostic nomogram for Hürthle cell thyroid carcinoma: a SEER-based study.

Background: Hürthle cell carcinoma is a rare subtype of thyroid cancer, and its clinical behavior and biological characteristics remain unclear. This study aimed to establish nomogram models for the prognostic evaluation of Hürthle cell thyroid carcinoma (HCTC) in terms of both cancer-specific survival (CSS) and overall survival (OS). Methods: Data for a total of 3,264 patients with HCTC (2004 to 2018) were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression analysis was performed to identify significant predictors of prognosis and develop a prognostic nomogram. The performance of the model was assessed based on the area under the receiver operating characteristic curve (AUC), concordance index (c-index), and calibration curves. Results: Multivariate Cox regression analysis showed that age, sex, summary stage, tumor size, N stage, M stage, and treatment with thyroidectomy were independent predictors of OS. Moreover, age, summary stage, tumor size, N stage, M stage, AJCC stage, and treatment with thyroidectomy were significantly correlated with CSS. The c-index of the OS and CSS nomograms developed based on these factors was 0.822 (95% CI: 0.803-0.841) and 0.893 (95% CI: 0.866-0.920), respectively. The AUC was 0.888, 0.841, and 0.834 for 1-, 3-, and 5-year OS and 0.970, 0.949, and 0.933 for 1-, 3-, and 5-year CSS, respectively. The calibration curves showed good agreement between observed and predicted values. Moreover, decision curve analysis revealed that the nomogram had a better clinical utility than individual clinicopathological markers. Conclusions: A prognostic nomogram that allows the individualized assessment of OS and CSS in HCTC was developed. This nomogram could be used to guide treatment decisions in patients with HCTC.

Evaluation of Ferroptosis-related Gene AKR1C1 as a Novel Biomarker Associated with the Immune Microenvironment and Prognosis in Breast Cancer.

BACKGROUND: Ferroptosis is the latest-discovered, iron-dependent form of regulated cell death. It has been increasingly recognized that ferroptosis-related genes participate in oncogenesis and development of cancers, including breast cancer (BRCA). Thus, It is important to explore the biofunctions of ferroptosis-related genes in BRCA. METHODS: Transcriptome microarray datasets (GSE22358, GSE9014 and GSE8977, GSE2990 and GSE2034) and TCGA-BRCA were retrieved for analyses. And a variety of computational tools were used to identify the roles and associated biological functions in BRCA. RESULTS: Two ferroptosis-related genes (AKR1C1 and AKR1C3) were significantly expressed in GSE22358, GSE9014 and GSE8977. Higher expression of AKR1C1 was related with favorable prognosis. TCGA-BRCA further confirmed the expression of AKR1C1 and the prognostic value of AKR1C1. Co-expression analyses showed the most enriched GO term and KEGG pathways were termination of DNA-templated transcription and Fanconi anemia pathway. Subsequently, immunological analyses showed AKR1C1 was significantly associated with various immune infiltration cells; among these, dendritic cells, neutrophils, macrophages were the top three infiltrating cells. Furthermore, AKR1C1 was also associated with multiple immunostimulatory molecules and chemokines, including PD-1, PD-L1, CTLA4, B7-H3, VSIR, IL-6, BTLA, CXCL2, and CCR7. These results indicated the potential roles of AKR1C1 in the immune reaction during the pathogenesis of breast cancer. CONCLUSION: This study firstly demonstrated that ferroptosis-related gene, AKR1C1, could be associated with immune microenvironment, thereby influencing the development and prognosis of patient with breast cancer.

The Role of m6A RNA Methylation-Related lncRNAs in the Prognosis and Tumor Immune Microenvironment of Papillary Thyroid Carcinoma.

Emerging evidence has indicated that N6-methylandenosine (m6A) RNA methylation plays a critical role in cancer development. However, the function of m6A RNA methylation-related long noncoding RNAs (m6A-lncRNAs) in papillary thyroid carcinoma (PTC) has never been reported. This study aimed to investigate the role of m6A-lncRNAs in the prognosis and tumor microenvironment (TME) of PTC. Three subgroups (clusters 1, 2, and 3) were identified by consensus clustering of 19 prognosis-related m6A-lncRNA regulators, of which cluster 1 is preferentially related to unfavorable prognosis, lower immune scores, and distinct immune infiltrate level. A risk-score model was established based on 8 prognosis-related m6A-lncRNAs. Patients with a high-risk score showed a worse prognosis, and the ROC indicated a reliable prediction performance for patients with PTC (AUC = 0.802). As expected, the immune scores, the infiltration levels of immune cells, and ESTIMATE scores in the low-risk subgroups were notably higher (p < 0.001) when compared with those in high-risk subgroups. Furthermore, GSEA analysis revealed that tumor associated pathways, hallmarks, and biological processes were remarkably enriched in the high-risk subgroup. Further analysis indicated that the risk score and age were independent prognostic factors for PTC. An integrated nomogram was constructed that accurately predicted the survival status (AUC = 0.963). Moreover, a lncRNA-miRNA-mRNA regulated network was established based on seven prognosis-related m6A-lncRNAs. In addition, 30 clinical samples and different PTC cells were validated. This is the first study to reveal that m6A-lncRNAs plays a vital role in the prognosis and TME of PTC. To a certain degree, m6A-lncRNAs can be considered as new, promising prognostic biomarkers and treatment targets.