Correction: Liu et al. Endostatin 33 Peptide Is a Deintegrin α6ß1 Agent That Exerts Antitumor Activity by Inhibiting the PI3K-Akt Signaling Pathway in Prostate Cancer. J. Clin. Med. 2023, 12, 1861.

In the original publication [...].

Multi-omics comprehensive analysis reveals the predictive value of N6-methyladenosine- related genes in prognosis and immune escape of bladder cancer.

BACKGROUND: N6-methyladenosine (m6A) is the most frequent RNA modification in mammals, and its role in bladder cancer (BC) remains rarely revealed. OBJECTIVE: To predict the value of m6A-related genes in prognosis and immunity in BC. METHODS: We performed multiple omics analysis of 618 TCGA and GEO patients and used principal component analysis (PCA) to calculate the m6A score for BC patients. RESULTS: We described the multiple omics status of 23 m6A methylation-related genes (MRGs), and four m6A clusters were identified, which showed significant differences in immune infiltration and biological pathways. Next, we intersected the differential genes among m6A clusters, and 11 survival-related genes were identified, which were used to calculate the m6A score for the patients. We found that the high-score (HS) group showed lower tumor mutation burden (TMB) and TP53 mutations and better prognosis than the low-score (LS) group. Lower immune infiltration, higher expression of PD-L1, PD-1, and CTLA4, and higher immune dysfunction and immune exclusion scores were identified in the LS group, suggesting a higher possibility of immune escape. Finally, the experimental verification shows that the m6A related genes, such as IGFBP1, plays an important role in the growth and metastasis of bladder cancer. CONCLUSIONS: These findings revealed the important roles of m6A MRGs in predicting prognosis, TMB status, TP53 mutation, immune functions and immunotherapeutic response in BC.

A new immune-related gene signature predicts the prognosis and immune escape of bladder cancer.

BACKGROUND: The biological roles of immune-related genes (IRGs) in bladder cancer (BC) need to be further elucidated. OBJECTIVE: To elucidate the predictive value of IRGs for prognosis and immune escape in BC. METHODS: We comprehensively analyzed the transcriptomic and clinical information of 430 cases, including 19 normal and 411 BC patients from the TCGA database, and verified 165 BC cases in the GSE13507 dataset. The risk model was constructed based on IRGs by applying LASSO Cox regression and exploring the relationship between the risk score and prognosis, gene mutations, and immune escape in BC patients. RESULTS: We identified 4 survival-related genes (PSMC1, RAC3, ROBO2 and ITGB3) among 6,196 IRGs in both the TCGA and GES13507 datasets,, which were used to establish a gene risk model by applying LASSO Cox regression. The results showed that the high-risk (HR) group was closely associated with poor survival or advanced pathological stage of BC. Furthermore, the risk score was found to be an independent risk factor for prognosis of BC patients. In addition, high-risk individuals showed a greater prevalence of TP53 mutations lower CD8+ T-cell and NK cell infiltration, higher Treg cell infiltration, higher expression of PD-L1, and higher immune exclusion scores than those in the low-risk (LR) group. Finally, the experimental verification shows that the model construction gene, especially PMSC1, plays an important role in the growth and metastasis of bladder cancer. CONCLUSIONS: These evidences revealed the vital role of IRGs in predicting prognosis, TP53 mutation and immune escape in BC patients.

Endostatin 33 Peptide Is a Deintegrin α6ß1 Agent That Exerts Antitumor Activity by Inhibiting the PI3K-Akt Signaling Pathway in Prostate Cancer.

BACKGROUND: Prostate cancer (PCa) is the leading cause of death in men and has poor therapeutic outcomes. METHODS: A novel endostatin 33 peptide was synthesized by adding a specific QRD sequence on the basis of the endostatin 30 peptide (PEP06) with antitumor activity. Then, bioinformatic analysis and subsequent experiments were performed to validate the antitumor function of this endostatin 33 peptide. RESULTS: We found that the 33 polypeptides significantly inhibited growth, invasion and metastasis and promoted the apoptosis of PCa in vivo or vitro, which is more significant than PEP06 under the same conditions. According to 489 cases from the TCGA data portal, the α6ß1 high expression group was closely associated with the poor prognosis (Gleason score, pathological N stage, etc.) of PCa and was mainly enriched in the PI3K-Akt pathway. Subsequently, we demonstrated that endostatin 33 peptide can down-regulate the PI3K-Akt pathway via the targeted inhibition of α6ß1, thereby inhibiting the epithelial-mesenchymal transition and matrix metalloproteinase in C42 cell lines. CONCLUSION: The endostatin 33 peptide can exert antitumor effects by inhibiting the PI3K-Akt pathway, especially in tumors with a high expression of the integrin α6ß1 subtype, such as prostate cancer. Therefore, our study will provide a new method and theoretical basis for the treatment of prostate cancer.

The predictive value of pyroptosis for the prognosis and immune escape of bladder cancer.

OBJECTIVE: To evaluate the predictive value of pyroptosis-related genes for the prognosis and immune escape of bladder cancer (BC). METHODS: Transcriptomic and single nucleotide polymorphisms (SNPs) data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) portal. Least absolute shrinkage and selection operator (LASSO) analysis was carried out to construct a prognostic risk model for BC patients. RESULTS: Based on the expression of 50 pyroptosis-related genes, BC patients from TCGA database were divided into two clusters, which showed significant differences in overall survival and disease specific survival. Furthermore, we intersected the differentially expressed genes between these two clusters with those identified from the GSE13507 dataset and finally identified eight survival related genes, which was used to construct a prognostic risk model by LASSO Cox regression. According to the model, the high-risk (HR) group was closely associated with poor survival or the advanced pathological stage of BC. In addition, the HR group was mainly enriched in cell cycle and immune-related pathways and had a higher TP53 mutation rate than the low-risk (LR) group. Furthermore, these two risk groups were significantly related to immune cell composition, immune cell infiltration, and immune response. Importantly, a higher expression of PD-1, PD-L1, and CTLA4 as well as higher immune exclusion scores were found in the HR group, suggesting a higher possibility of immune escape. CONCLUSION: Our studies revealed the key role of pyroptosis in predicting the prognosis, TP53 mutation, and immune escape of patients with BC.