Leveraging a disulfidptosis-based signature to improve the survival and drug sensitivity of bladder cancer patients

Abstract

BackgroundDisulfidptosis is a recently discovered form of cell death. However, its biological mechanisms in bladder cancer (BCa) are yet to be understood.MethodsDisulfidptosis-related clusters were identified by consensus clustering. A disulfidptosis-related gene (DRG) prognostic model was established and verified in various datasets. A series of experiments including qRT-PCR, immunoblotting, IHC, CCK-8, EdU, wound-healing, transwell, dual-luciferase reporter, and ChIP assays were used to study the biological functions.ResultsWe identified two DRG clusters, which exhibited distinct clinicopathological features, prognosis, and tumor immune microenvironment (TIME) landscapes. A DRG prognostic model with ten features (DCBLD2, JAM3, CSPG4, SCEL, GOLGA8A, CNTN1, APLP1, PTPRR, POU5F1, CTSE) was established and verified in several external datasets in terms of prognosis and immunotherapy response prediction. BCa patients with high DRG scores may be characterized by declined survival, inflamed TIME, and elevated tumor mutation burden. Besides, the correlation between DRG score and immune checkpoint genes and chemoradiotherapy-related genes indicated the implication of the model in personalized therapy. Furthermore, random survival forest analysis was performed to select the top important features within the model: POU5F1 and CTSE. qRT-PCR, immunoblotting, and immunohistochemistry assays showed the enhanced expression of CTSE in BCa tumor tissues. A series of phenotypic assays revealed the oncogenetic roles of CTSE in BCa cells. Mechanically, POU5F1 can transactivate CTSE, promoting BCa cell proliferation and metastasis.ConclusionsOur study highlighted the disulfidptosis in the regulation of tumor progression, sensitivity to therapy, and survival of BCa patients. POU5F1 and CTSE may be potential therapeutic targets for the clinical treatment of BCa.

Analysis of network expression and immune infiltration of disulfidptosis‐related genes in chronic obstructive pulmonary disease

“…This data set comprises 32 samples, including 9 controls and 23 COPD patients. Additionally, the DRGs (FLNA, TLN1, PRDX1, MYH9, FLNB, ACTB, SLC7A11, RPN1, NCKAP1, NUBPL, NDUFA11, LRPPRC, OXSM, NDUFS1, and GYS1) were obtained from previous literature 21,22 . Detailed information about these genes is provided in Supporting Information: Table .…”

Multi‐omics analysis of disulfidptosis regulators and therapeutic potential reveals glycogen synthase 1 as a disulfidptosis triggering target for triple‐negative breast cancer

“…Previous studies have explored molecular and clinical characteristics of various forms of cell death in tumors, and disulfidptosis-based studies have been studied in oncological and non-oncological diseases at multi-omics levels. [13][14][15][16] Novel therapeutic targets can be identified and personalized treatment strategies can be developed mechanism of disulfidptosis. It is imperative for future research to focus on potential action mechanisms of disulfidptosis regulators in tumor development to improve patient outcomes.…”

circRNA TATA‐box binding protein associated factor 15 acts as an oncogene to facilitate bladder cancer progression through targeting miR‐502‐5p/high mobility group box 3

“…Patients with muscle‐invasive bladder cancer account for about 30% of all bladder cancer patients but have a high degree of malignancy, such as invasiveness, metastasis, drug resistance, and high recurrence rate. Thus, the survival rate of patients with muscle‐invasive bladder cancer is extremely low 2,3 . About 76,960 persons are newly diagnosed with bladder cancer, and 16,390 persons die of this malignancy annually in the United States 4 .…”