Muscle invasion in bladder cancer is associated with increased expression of ATG5, LC3A and CHOP.

BACKGROUND

Bladder cancer (BC) is considered one of the most prevalent malignant cancers of the urinary system. Recently, autophagy was found to be involved in tumor development.

OBJECTIVES

Investigating the link between BC and autophagy, highlighting the role of ER stress in tumor growth and invasiveness.

METHODS

Sixty urothelial carcinoma patients recruited to this study were divided into 2 groups: Low-grade BC (LGBC) and High-grade BC (HGBC), which were further classified as muscle-invasive (HGMI) or non-muscle-invasive (HGNMI). Control tissue samples were collected from the safety margin. Levels of ATG5 and caspase 3 were determined using qRT-PCR; CHOP levels by ELISA; and malondialdehyde using the lipid peroxide assay kit. LC3A expression was detected by immunohistochemistry.

RESULTS

Significant upregulation of tissue levels of ATG5, CHOP, MDA and LC3A was observed in tumor tissue samples from all groups compared to control, and in MIBC compared to NMIBC, with significant relations between their levels and LN involvement. Caspase-3 was significantly downregulated in HGBC compared to LGBC. Levels of ATG5, CHOP and LC3A can discriminate between normal and malignant urothelial tissue and between invasive and non-invasive bladder cancer.

CONCLUSION

Expression of tissue autophagy biomarkers is associated with aggressive clinicopathological features (muscle invasion) in bladder cancer.