Increasing evidence highlights the role of aberrant circadian rhythm gene expression in glioblastoma (GBM) progression, but the impact of the circadian rhythm gene network on GBM molecular profiles and prognosis remains unclear. A total of 1042 GBM samples from six public datasets, TCGA and CGGA, were analyzed, with GBM samples stratified into three circadian core-gene patterns using unsupervised clustering based on the expression profiles of 17 circadian rhythm genes. The Limma R package identified differentially expressed genes (DEGs) among the three patterns, and a secondary clustering system, termed circadian-related gene pattern, was established based on DEGs. A circadian risk score was constructed using the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm, and the efficiency of these patterns and the circadian risk score in distinguishing molecular profiles and predicting prognosis was systematically analyzed. The relationship between the circadian risk score and response to immune or targeted therapy was examined using the GSE78200 and IMvigor210 datasets. The results showed that GBM patients were clustered into three circadian core-gene patterns based on the expression profiles of 17 core circadian genes, with distinct molecular profiles, malignant characteristics, and patient prognoses among the patterns. Thirty-two DEGs among these patterns were identified and termed circadian-related genes, and secondary clustering based on these 32 DEGs classified GBM samples into two circadian-related gene patterns, which also predicted molecular profiles and prognosis. A circadian risk scoring system was established, allowing the calculation of individual risk scores based on the expression of 10 genes, where GBM patients with lower circadian risk scores had prolonged overall survival and less aggressive molecular subtypes, while higher circadian risk scores correlated with better responses to MAPK-targeted therapy. In conclusion, this study established two clustering patterns based on 17 circadian rhythm genes or 32 circadian-related genes, enabling the rapid classification of GBM patients with distinct molecular profiles and prognoses, while the circadian risk scoring system effectively predicted survival, molecular profiles, and therapeutic responses for individual GBM patients, demonstrating that the circadian rhythm gene network can distinguish molecular profiles and prognosis in GBM.

Background: Immunochemotherapy is increasingly adopted as neoadjuvant regimen for locally advanced esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the survival outcomes for those who achieved pathological complete response (pCR) following immunochemotherapy. Methods: From January 2020 and June 2025, 154 patients who achieved pCR after neoadjuvant immunochemotherapy were included for this analysis. We documented baseline patient characteristics, assessed survival outcomes, and designated disease-free survival (DFS) as the primary endpoint. Results: Of the 154 patients, there were 47 (30.5%) patients received chemotherapy combined with pembrolizumab, 37 (24.0%) with tislelizumab, 31 (20.1%) with sintilimab, 26 (16.9%) combined with camrelizumab, and 13 (8.4%) with other immune checkpoint inhibitors. Majority of the patients (74.1%, 114/154) had two treatment cycles. There were 81 patients (52.6%) underwent McKeown procedure and 73 (47.4%) underwent Ivor Lewis procedure, with the median of 30 lymph nodes resected. After a median follow-up of 25 months, the 1-year and 3-year DFS were 97% and 78%, respectively, the 1-year and 3-year overall survival were 97% and 88%, respectively. Advanced clinical tumor stage (hazard ratio [HR] = 4.831, 95% confidence interval [CI] 1.748–13.347, P = 0.002), more than two treatment cycles, (HR = 3.449, 95% CI 1.168–10.179, P = 0.025), and a treatment-to-surgery less than 6 weeks (HR = 5.344, 95% CI 1.198–23.840, P = 0.028) were associated with reduced DFS. Conclusion: ESCC patients achieving pCR after immunochemotherapy had favorable survival outcomes, yet disease recurrence remains a notable concern. Advanced tumor stage, increased number of treatment cycles and shortened interval between neoadjuvant treatment and surgery were associated with compromised survival in this patient population. These exploratory findings may help guide future prospective studies.