ABSTRACT
Bladder cancer (BC), as a genitourinary system tumor, is a highly prevalent tumor type. Ferroptosis is an iron-dependent oxidative cell death mechanism that is becoming increasingly recognized as a promising avenue for cancer therapy. However, further determination of the prospective prognostic value of ferroptosis for BC and investigation of the underlying mechanisms is required. The mRNA expression profiles and associated clinical data were downloaded from public databases such as The Cancer Genome Atlas, Gene Expression Omnibus and the IMvigor210 database. To construct a predictive formula, the least absolute shrinkage and selection operator Cox regression algorithm was used. In addition, a prognostic multigene signature was constructed using previously selected ferroptosis-related genes (FRGs). A total of 28 FRGs were differentially expressed between tumor and normal samples with |log2 fold change| >1 and adjusted P<0.05. A prognostic model was then established and it was validated in the GEO cohort using six genes: Glutamate-cysteine ligase modifier subunit, crystallin α-B, transferrin receptor, zinc finger E-box binding homeobox 1, squalene epoxidase and glucose-6-phosphate dehydrogenase (G6PD). Numerous important pathways involved in the development of the immune system and cancer were indicated to be significantly different between the two risk groups. In addition, it was discovered that G6PD expression subgroups that were associated with immunotherapy response in patients with BC had similar prognostic features to risk score subgroups. In the present study, a gene signature with a prognostic value for ferroptosis in BC was successfully developed and the potential value of G6PD was identified for future research.
ABSTRACT
PURPOSE: In this study, we aimed to investigate the viability of utilizing CytoSorter® system to detect circulating tumor cells (CTCs) and to evaluate the diagnostic value of CTCs in breast cancer (BC). METHODS: A total of 366 females patients suspected of having BC and 30 healthy female volunteers were enrolled in this study. CTCs were enriched by CytoSorter® , a microfluidic-based CTCs capturing platform. CTC detection was performed before operation or biopsy. Based on the biopsy results, patients were divided into two groups, namely patients with BC and patients with benign breast diseases (BBD). Patients with BBD and healthy volunteers were serving as controls. The correlation between CTC enumeration and patients' clinicopathological characteristics was evaluated. The receiver operating characteristic (ROC) curve was plotted to assess the diagnostic potency of CytoSorter® system in BC. RESULTS: Based on the biopsy results, 130 BC patients at different cancer stages and 236 patients with BBD were enrolled in the study. Seven subjects were dropped out from the study. CTCs were detected in 109 of 128 BC patients, in one of 29 healthy volunteers, and in 37 of 232 patients with BBD. Maximum CTC counts detected in BC patients, healthy volunteers, and patients with BBD were 8, 1, and 4, respectively. Statistical analysis showed CTCs could be used to distinguish BC patients from healthy volunteers and patients with BBD (P < .0001). Circulating tumor cells were statistically associated with patients' cancer stage (P = .0126), tumor size (tumor node metastasis [TNM] T stage, P = .0253), cancer type (invasive vs noninvasive, P = .0141), and lymph node metastasis (P = .0436). More CTCs were found in patients at advanced cancer stage or TNM T stage and in patients with invasive tumor or lymph node metastasis. Furthermore, CTC detection rates in BC patients at Tis and T1-4 stages were 50%, 81.67%, 91.07%, 100%, and 100%, respectively. When the CTC cut-off value was set to 2, the ROC curve gave an area under the curve (AUC) of 0.86 with a specificity and sensitivity of 95.4% and 76.56%, respectively. Taken together, CTCs could be used as a diagnostic aid in assistance of cancer screening and staging. CONCLUSION: Circulating tumor cells were successfully isolated in BC patients using CytoSorter® system. CTCs can be used to differentiate BC patients from the patients with BBD or healthy volunteers, and as a diagnostic aid for early cancer diagnosis and cancer staging.
