Ferroptosis: An Emerging Target for Bladder Cancer Therapy.

Bladder cancer (BC), as one of the main urological cancers in the world, possesses the abilities of multiple-drug resistance and metastasis. However, there remains a significant gap in the understanding and advancement of prognosis and therapeutic strategies for BC. Ferroptosis, a novel type of iron-dependent regulated cell death, depends on lipid peroxidation, which has been proven to have a strong correlation with the development and treatment of BC. Its mechanism mainly includes three pathways, namely, lipid peroxidation, the antioxidant system, and the iron overload pathway. In this review, we reviewed the mechanism of ferroptosis, along with the related therapeutic targets and drugs for BC, as it might become a new anticancer treatment in the future.

Comprehensive analysis of the prognosis and immune infiltration of TMC family members in renal clear cell carcinoma.

Renal cancer is a common malignancy of the urinary system, and renal clear cell carcinoma (RCCC) is the most common pathological type. Transmembrane channel-like (TMC) protein is an evolutionarily conserved gene family containing 8 members, however there is still a lack of comprehensive analysis about TMC family members in RCCC. In this study, we analyzed the expression of TMC family members in RCCC from TCGA and investigated the prognosis values and immune infiltration of TMC family members in RCCC. We found that TMC2, TMC3, TMC5, TMC7 and TMC8 were significantly related with overall survival (OS) of RCCC patients. TMC3, TMC6, and TMC8 was positively correlated with the degree of immune infiltration in RCCC. TMC2, TMC6, TMC7, and TMC8 were positively correlated with immune checkpoint genes, whereas TMC4 was negative. According to KEGG and GO analysis, almost all TMCs except TMC4 were involved in the immune response. Thus, we may regard the TMC family members as novel biomarkers to predict potential prognosis and immunotherapeutic response in RCCC patients.

Insights into prognosis and immune infiltration of cuproptosis-related genes in breast cancer.

Introduction: Breast cancer (BC) has been ranking first in incidence and the leading cause of death among female cancers worldwide based on the latest report. Regulated cell death (RCD) plays a significant role in tumor initiation and provides an important target of cancer treatment. Cuproptosis, a novel form of RCD, is ignited by mitochondrial stress, particularly the lipoylated mitochondrial enzymes aggregation. However, the role of cuproptosis-related genes (CRGs) in tumor generation and progression remains unclear. Methods: In this study, the mRNA expression data of CRGs in BC and normal breast tissue were extracted from TCGA database, and protein expression patterns of these CRGs were analyzed using UALCAN. The prognostic values of CRGs in BC were explored by using KaplanMeier plotter and Cox regression analysis. Genetic mutations profiles were evaluated using the cBioPortal database. Meanwhile, we utilized CIBERSORT and TIMER 2.0 database to perform the correlation analysis between CRGs and immune cell infiltration. Results: Our results indicated that CRGs expression is significantly different in BC and normal breast tissues. Then we found that upregulated PDHA1 expression was associated with worse endpoint of BC. Moreover, we also performed immune infiltration analysis of CRGs, and demonstrated that PDHA1 expression was closely related to the infiltration levels of CD4+ memory T cell, macrophage M0 and M1 cell and mast cell in BC. Conclusions: Our results demonstrated the prognostic and immunogenetic values of PDHA1 in BC. Therefore, PDHA1 can be an independent prognostic biomarker and potential target for immunotherapy of BC.

Pan-cancer analysis of FBXW family with potential implications in prognosis and immune infiltration.

Background: The F-box and WD repeat domain containing (FBXW) family of SCF E3 complexes has 10 members that are responsible for ubiquitination and degradation of substrate proteins involved in cell cycle regulation and tumorigenesis. Among them, FBXW1 (also called b-TrCP1/BTRC) and FBXW7 are the central proteins in this category. However, there is still a lack of elaborate exploration of the contribution of FBXW family members, especially FBXW1 and FBXW7, in various tumor types. Methods: In this present study, we preliminarily analyzed the genetic structure characteristics of the FBXW family, and systematically investigated their expression patterns and clinical correlations based on the TCGA pan-cancer data. Survival analysis of FBXWs was also conducted through the Kaplan-Meier method. In addition, we assessed their immune infiltration level through immune-related algorithms like Timer and xCell. Results: There were obvious genetic heterogeneity and different clinical traits in FBXW family members. Moreover, we found that FBXW family genes may be useful in predicting prognosis and therapeutic efficacy using survival analysis. In addition, the immune infiltration of FBXW family was also clearly illustrated in this study. The results showed these genes were closely involved in immune components such as immune score, immune subtypes, tumor-infiltrating lymphocytes and immune checkpoints. Notedly, FBXW1 as an oncogene and FBXW7 as a tumor suppressor gene also show opposite relationships on immune cells. Conclusion: Our results provided valuable strategies to guide the therapeutic orientation concerning the role of FBXW family genes in cancer.