Estimating disease-free survival of thyroid cancer based on novel cuprotosis-related gene model.

Background: Cuprotosis is a newly discovered form of cell death that differs from other types of cell death. The aim of this study was to investigate the functional role and a possible prognostic model for thyroid cancer. Methods: TCGA and GEO were used to investigate the differential expression of CRGs in THCA. KEGG and GO enrichment analyses were applied to investigate the possible molecular functions. The features of CRGs were selected by LASSO regression. 20 pairs of samples were randomly collected from the hospital to compare expression between tumor and normal. Results: Among the 19 CRGs related to thyroid cancer recurrence, 16 genes were differentially expressed in thyroid cancer. KEGG analysis showed that the 19 CRGs were mainly enriched in cell death, cell cycle and ribosomal pathways. K-M survival analysis and subsequent multiple logistic regression revealed that the expression of BUB1 and GINS2 were potential risk factors for disease-free survival (DFS) of thyroid cancer. In addition, further LASSO-regression selected the following three DFS-related CRGs: FDX1, BUB1 and RPL3. A novel prognostic prediction model was constructed by nomogram, and the prediction probability for 1-, 3- and 5-year survival approached the actual time. As for the possible mechanisms, FDX1, BUB1 and RPL3 were associated with immune infiltration. The cell model experiment illustrated that the ATM signaling pathway might be involved in thyroid cancer cell death. Conclusion: Three CRG models (FDX1, BUB1, RPL3) could better predict the prognosis of thyroid cancer. Immune cell infiltration and the ATM pathway were the possible mechanisms.

Pan-Cancer Analysis of the Oncogenic and Prognostic Role of PKM2: A Potential Target for Survival and Immunotherapy.

Background: No pan-cancer study has been conducted till date to explore the comprehensive oncogenic roles of pyruvate kinase M2 (PKM2). Methods: TCGA, TIMER, GEPIA, UALCAN, STRING, and other databases were used to analyze the expression, prognostic roles, epigenetic variants, and possible oncogenic mechanisms of PKM2. Proteomic sequencing data and PRM were applied to validate. Results: PKM2 showed higher expression in majority of cancers, the expression being significantly correlated with the clinical stage. Higher expression of PKM2 was associated with lower OS and DFS in several cancers, such as MESO and PAAD. In addition, the epigenetic variation of PKM2, including gene alteration, mutation type and sites, DNA methylation, and phosphorylation, showed diversity in different cancers. All four methods indicated that PKM2 is positively associated with the immune infiltration of tumor-associated fibroblasts, such as in THCA, GBM, and SARC. Further mechanistic exploration suggested that the ribosome pathway might play an essential role in the regulation of PKM2, and interestingly, four out of ten hub genes were found to be highly related to OS in several cancers. Finally, in thyroid cancer specimen, we validated the expression and potential mechanisms by proteomic sequencing and PRM validation. Conclusion: In the majority of cancers, the higher expression of PKM2 was highly associated with poor prognosis. Further molecular mechanism exploration implied that PKM2 might serve as a potential target for cancer survival and immunotherapy by regulating the ribosome pathway.

A Comprehensive Analysis of KRT19 Combined with Immune Infiltration to Predict Breast Cancer Prognosis.

To date, no study has been conducted to explore the mechanism of KRT19 and the correlation between the expression of KRT19 and immune infiltration in breast cancer (BRCA). TCGA, TIMER2.0, UALCAN, and other databases were used to analyze the expression, prognostic roles, epigenetic variants, and possible oncogenic mechanisms of KRT19 in BRCA. As a result, KRT19 showed higher expression compared with the normal tissues in BRCA. In addition, the epigenetic variation in KRT19, including gene alteration, mutation type and sites, DNA methylation, RNA modification, and phosphorylation, showed diversity in BRCA. Further mechanistic exploration suggested that the IL-17 signaling pathway and estrogen response might play essential roles in the regulation of KRT19. Moreover, KRT19 has different regulatory biological functions in BRCA. More importantly, the expression of KRT19 was closely related to immune infiltration and combining the two could effectively predict overall survival. Finally, a nomogram based on genes associated with cancer-immunity cycle signatures, which could predict progress free interval, was constructed and evaluated successfully. In conclusion, KRT19 may play a role in the occurrence and development of BRCA through the IL-17 signaling pathway. Meanwhile, KRT19 combined with immune infiltration can evaluate the prognosis of BRCA patients.