Abstract
Clear cell adenocarcinoma (CCA) is a rare variant of urinary bladder carcinoma with a glycogen-rich phenotype and unknown prognosis. Using the National Cancer Institute’s surveillance, epidemiology, and end results (SEER) program database, we documented recent trends in incidence, mortality, demographical characteristics, and survival on this rare subtype of urinary bladder cancer. The overall age-adjusted incidence and mortality of CCA was 0.087 (95% confidence interval (CI): 0.069–0.107) and 0.064 (95% CI: 0.049–0.081) respectively per million population. In comparison to non-CCAs, CCAs were more commonly associated with younger age (<60 years old, p = 0.005), female (p < 0.001), black ethnicity (p = 0.001), grade III (p < 0.001), and higher AJCC 6th staging (p < 0.001). In addition, CCA patients more frequently received complete cystectomy (p < 0.001) and beam radiation (p < 0.001) than non-CCA patients. Our study showed a poorer prognosis of CCAs compared to all other carcinomas of the urinary bladder (p < 0.001), accounted for by higher tumor staging of CCA cases. This study adds to the growing evidence that glycogen-rich cancers may have unique characteristics affecting tumor aggressiveness and patient prognosis. Additional mechanistic studies are needed to assess whether it’s the excess glycogen that contributes to the higher stage at diagnosis.
Highlights
Glycogen, a multibranched polymer of glucose, serves as our body’s main form of carbohydrate storage [1]
Using 91 cases of cell adenocarcinoma (CCA) and 205,106 cases of other urinary bladder cancers obtained from the SEER Program database, we identified a poorer prognosis attributed to higher staging at time for diagnosis for CCAs
To assess recent trends in the incidence and mortality of CCA, we queried all cases of CCA from 2004 to 2015 in the SEER Program database
Summary
A multibranched polymer of glucose, serves as our body’s main form of carbohydrate storage [1]. Glycogen has become well-established that, in addition to its role in maintaining metabolic homeostasis in normal cells, it has a crucial role in promoting tumor growth, especially under adverse conditions [2]. Under hypoxic conditions, which are commonly encountered by tumors cells, expression of transcription factor HIF1α increases glycogen accumulation [3]. Glycogen has been proposed to maintain the Warburg effect in tumor cells, providing a mechanism for survival during nutrient deprivation [5]. Glycogen’s inability to metabolize glycogen through small molecule inhibitors was able to induce apoptosis or senescence in tumor cells [6,7]. Cancer cells utilize glycogen as a way to alter its metabolic programing in order to adapt to the adverse tumor microenvironment and maintain tumor growth
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