Stepwise molecular mechanisms responsible for chemoresistance in bladder cancer cells.
Jeong-Yeon MunSeung-Woo BaekMi-So JeongIn-Hwan JangSe-Ra LeeJae-Young YouJeong-Ah KimGi-Eun YangYung-Hyun ChoiTae-Nam KimIn-Sun ChuSun-Hee LeemPublished in: Cell death discovery (2022)
Chemotherapy resistance is an obstacle to cancer therapy and is considered a major cause of recurrence. Thus, understanding the mechanisms of chemoresistance is critical to improving the prognosis of patients. Here, we have established a stepwise gemcitabine-resistant T24 bladder cancer cell line to understand the molecular mechanisms of chemoresistance within cancer cells. The characteristics of the stepwise chemoresistance cell line were divided into 4 phases (parental, early, intermediate, and late phases). These four phase cells showed increasingly aggressive phenotypes in vitro and in vivo experiments with increasing phases and revealed the molecular properties of the biological process from parent cells to phased gemcitabine-resistant cell line (GRC). Taken together, through the analysis of gene expression profile data, we have characterized gene set of each phase indicating the response to anticancer drug treatment. Specifically, we identified a multigene signature (23 genes including GATA3, APOBEC3G, NT5E, MYC, STC1, FOXD1, SMAD9) and developed a chemoresistance score consisting of that could predict eventual responsiveness to gemcitabine treatment. Our data will contribute to predicting chemoresistance and improving the prognosis of bladder cancer patients.
Keyphrases
- induced apoptosis
- cell cycle arrest
- cancer therapy
- locally advanced
- genome wide
- end stage renal disease
- oxidative stress
- squamous cell carcinoma
- copy number
- endoplasmic reticulum stress
- electronic health record
- gene expression
- spinal cord injury
- dna methylation
- emergency department
- signaling pathway
- peritoneal dialysis
- deep learning
- prognostic factors
- transforming growth factor
- replacement therapy