The efficacy of immune checkpoint inhibitors therapy versus chemotherapy in the treatment of advanced and metastatic urothelial carcinoma: a meta-analysis.

PURPOSE: The application of platinum-based chemotherapeutic agents is the traditional treatment paradigm for advanced and metastatic urothelial carcinoma, which has changed with the advent of immune checkpoint inhibitors (ICIs). This study aims to evaluate the efficacy of ICI therapy versus chemotherapy in the treatment of advanced and metastatic urothelial carcinoma. METHODS: A systematic literature search of Web of Science, Embase, PubMed, and Cochrane Central Register of Controlled Trials was performed by two independent investigators. The primary endpoint was overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). RESULTS: The patients treated with ICI monotherapy had no significant difference in OS than those treated with chemotherapy monotherapy (HR: 0.965, 95% CI 0.865-1.076, p = 0.518). However, the patients treated with ICI monotherapy had a higher ORR and lower incidence of high-grade (≥ grade 3) AEs than those treated with chemotherapy monotherapy (OR: 0.568, 95% CI 0.479-0.675, p < 0.001; OR: 0.614, 95% CI 0.446-0.845, p = 0.003). The patients treated with ICI in combination with chemotherapy had significantly better OS and PFS than those treated with chemotherapy alone (HR: 0.862, 95% CI 0.776-0.957, p = 0.006; HR: 0.788, 95% CI 0.707-0.879, p < 0.001). However, there was no significant difference in ORR or the incidence of grade 3 or higher AEs (OR: 0.951, 95% CI 0.582-1.554, p = 0.841; OR: 0.942, 95% CI 0.836-1.062, p = 0.328). CONCLUSION: ICI monotherapy did not show statistically significant difference in OS but demonstrated higher ORR and lower incidence of high-grade (≥ grade 3) AEs. And a statistically significant OS and PFS benefit was found in patients treated with first-line ICI in combination with chemotherapy compared to chemotherapy alone.

Circ-SHPRH in human cancers: a systematic review and meta-analysis.

Circular RNA (circRNA) molecules are noncoding RNAs with ring-like structures formed by covalent bonds and are characterized by no 5'caps or 3'polyadenylated tails. Increasing evidence shows that circRNAs may play an important role in tumorigenesis and cancer metastasis. Circ-SHPRH originates from exons 26-29 of the SHPRH gene, and it is closely associated with human cancers. We searched PubMed, Web of Science, and Embase databases for relevant literatures until 24 December 2022. Eighteen research papers were included in this review, and 11 papers were selected for meta-analysis after screening. Three eligible published studies about circ-SHPRH were enrolled based on their tumor diagnosis aspect, 7 eligible published studies were related to overall survival (OS), and 3 eligible published studies were related to tumor grade. Many studies have shown that circ-SHPRH acts as a miRNA sponge or encodes a protein to regulate downstream genes or signal pathways, and exerts specific biological functions that affect the proliferation, invasion, and apoptosis of cancer cells. Meta-analysis showed that patients with high expression of circ-SHPRH had better OS (HR = 0.53, 95% CI 0.38-0.74, p-value <0.05) and lower TNM stage (HR = 0.33, 95% CI 0.18-0.62, p-value = 0.001). In addition, circ-SHPRH has potential diagnostic value (AUC = 0.8357). This review will help enrich our understanding of the role and mechanism of circ-SHPRH in human cancers. Circ-SHPRH has the potential to be a novel diagnostic and prognostic biomarker for various solid cancers.

Research progress on PD-1 and PD-L1 inhibitors in the treatment of metastatic urothelial carcinoma.

Urothelial carcinoma (UC) is a very common malignant tumor. In the past few decades, platinum-based chemotherapy has been regarded as the standard recommended regimen for patients with metastatic urothelial carcinoma (mUC) who can receive either cisplatin or carboplatin. The emergence of immune checkpoint inhibitors (ICIs) brought some hope for possible treatments for mUC patients who were unfit for platinum therapy. ICIs drugs have emerged as new potential weapons to overcome UC in our lifetime. ICIs block the binding of programmed death-1 (PD-1) to programmed death-ligand 1 (PD-L1), leading to enhancement of the immune function of antitumor T cells. In the treatment of UC, ICIs show an apparent ascendancy and effectively enhance survival rates. With good tolerability and remarkable effects, ICIs have given thousands of patients hope. This article mainly shows the application of PD-1 and PD-L1 inhibitors in mUC.

CircSMARCA5: A key circular RNA in various human diseases.

Circular RNAs (circRNAs) are recognized as a novel type of single-stranded endogenous noncoding RNA molecule with the characteristics of tissue specificity, sequence conservation and structural stability. Accumulating studies have shown that circRNAs play a unique biological role in different kinds of diseases. CircRNAs can affect tumor proliferation, migration, metastasis and other behaviors by modulating the expression of downstream genes. CircSMARCA5, an example of a circRNA, is dysregulated in various noninfectious diseases, such as tumors, osteoporosis, atherosclerosis and coronary heart disease. Furthermore, recent studies have demonstrated that circSMARCA5 is associated with the occurrence and development of a variety of tumors, including gastric cancer, glioblastoma, hepatocellular carcinoma, multiple myeloma, colorectal cancer, breast cancer and osteosarcoma. Mechanistically, circSMARCA5 primarily acts as a sponge of miRNAs to regulate the expression of downstream genes, and can serve as a potential biomarker for the diagnosis of malignant tumors. This review summarizes the biological roles of circSMARCA5 and its molecular mechanism of action in various diseases. Moreover, the meta-analysis of some publications showed that the expression of circSMARCA5 was significantly correlated with the prognosis of patients and tumor TNM stage, showing that circSMARCA5 has the potential to be a prognostic marker.