TDO2 overexpression correlates with poor prognosis, cancer stemness, and resistance to cetuximab in bladder cancer

TDO2 过表达与膀胱癌预后不良、癌症干细胞特性及西妥昔单抗耐药性相关

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作者:Quoc Thang Pham, Daiki Taniyama, Shintaro Akabane, Kenji Harada, Takashi Babasaki, Yohei Sekino, Tetsuraro Hayashi, Naoya Sakamoto, Kazuhiro Sentani, Naohide Oue, Wataru Yasui

Aim

This study aim to investigate the clinicopathologic significance of TDO2 in BC.

Background

Bladder cancer (BC) is the 10th most common cancer in the world. BC with muscle invasion

Conclusion

Our results indicate that TDO2 might take an essential part in BC progression and could be a potential marker for targeted therapy in BC.

Results

TDO2 expression was evaluated by qRT-PCR and immunohistochemistry in an integrated analysis with the Cancer Genome Atlas (TCGA) and other published datasets. TDO2 overexpression was significantly associated with T classification, N classification, and M classification, tumor stage, recurrence, and basal type, and with the expression of CD44 and aldehyde dehydrogenase 1 (ALDH1) in BC. High TDO2 expression correlated with poor outcome of BC patients. Using BC cell lines with knockdown and forced expression of TDO2, we found that TDO2 was involved in the growth, migration, and invasiveness of BC cells. Moreover, TDO2 was found to be crucial for spheroid formation in BC cells. Importantly, TDO2 promoted BC cells resistance to cetuximab through integration of the EGFR pathway.

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