The clock gene PER1 plays an important role in regulating the clock gene network in human oral squamous cell carcinoma cells The clock gene PER1 plays an important role in regulating the clock gene network in human oral squamous cell carcinoma cells

Background: The effectiveness and safety of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors is controversial. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors as neoadjuvant therapy for malignant solid tumors. Methods: This study has been registered with the number CRD42023407275 on PROSPERO. Systematic searches were conducted in PubMed, Embase, Web of Science and Cochrane Library databases until March 17, 2023. In addition, manual searches were performed. The inclusion criteria encompassed randomized controlled trials (RCTs) that assessed the utilization of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors PD-1/PD-L1 inhibitors for patients with solid malignancies. The Cochrane Collaboration's tool for assessing risk of bias in randomized trials (ROB1) were used. Risk ratios (RRs), hazared ratios (HRs) and their respective 95% confidence intervals were calculated using Stata17.0 MP and Review Manager 5.4 software. Results: A total of 2780 records were identified, and ultimately 10 studies involving 273 patients were included. The meta-analysis showed that the addition of CTLA-4 inhibitors to PD-1/PD-L1 inhibitors did not demonstrate a significant effect on overall response rate, main pathological response, pathological complete response, surgical resection, radical resection, overall survival, progression-free survival, recurrence-free survival, grade 3–4 adverse events, all-cause mortality, and completed treatment (P > 0.05). However, further subgroup analysis indicated that the combination of PD-1 with CTLA-4 inhibitors significantly increased the occurrence of grade 3–4 adverse events in patients (P < 0.05). Conclusions: As neoadjuvant therapy for malignant solid tumors, the addition of CTLA-4 inhibitors to PD-1/PD-L1 inhibitors does not appear to enhance efficacy.Moreover, there is a potential increase in the risk of grade 3–4 adverse events associated with this combination. However, it is important to note that the studies included in this analysis suffer from limitations such as small samples and single-center designs, which are inherent constrains with the available published literature. Further research involving large-sample and multicenter RCTs are warranted to obtain more reliable results.

Background. Period genes are important core clock genes, including PER1, PER2, and PER3. A number of studies have demonstrated that the abnormal expression of the PER gene family of clock genes is associated with the survival and prognosis of patients with cancer; however, the sample sizes included in the majority of these studies were small, and the reported results were inconsistent. This study was the first to collect the relevant publications to systematically evaluate the value of the expression of the PER gene family in the prediction of survival and prognosis of human tumors. Methods. The PubMed, Cochrane Library, Embase, and Web of Science databases were searched systematically, and a meta-analysis was performed. Results. A total of 12 eligible publications met the inclusion criteria for the meta-analysis, including 1,369 patients and 9 different types of cancer. The pooled hazard ratio for overall survival indicated that the overall survival of patients in the high PER1, PER2, and PER3 protein expression group was significantly higher than that in the low-expression group, respectively. The sensitivity analysis revealed that the result was stable and reliable. The association between PER1 and PER3 mRNA expression levels and cancer prognosis was not meta-analyzed as the number of experimental studies was <3. There was no significant association between the expression of PER2 mRNA and the overall survival of patients with cancer. Conclusion. PER1, PER2, and PER3 protein expression levels can be used as novel potential biomarkers for predicting cancer prognosis.