Identification of the α2 chain of interleukin-13 receptor as a potential biomarker for predicting castration resistance of prostate cancer using patient-derived xenograft models

使用患者来源的异种移植模型鉴定白细胞介素-13 受体的 α2 链作为预测前列腺癌去势抵抗性的潜在生物标志物

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作者:Takahiro Nagai, Naoki Terada, Masato Fujii, Yasuhisa Nagata, Kozue Nakahara, Shoichiro Mukai, Kosuke Okasho, Yuki Kamiyama, Shusuke Akamatsu, Takashi Kobayashi, Kei Iida, Masatsugu Denawa, Masatoshi Hagiwara, Takahiro Inoue, Osamu Ogawa, Toshiyuki Kamoto

Background

Several treatment strategies use upfront chemotherapy or androgen receptor axis-targeting therapies for metastatic prostate cancer. However, there are no useful biomarkers for selecting appropriate patients who urgently require these treatments.

Conclusion

IL13Rα2 was highly expressed in castration-resistant prostate cancer PDX models and was associated with the castration resistance of prostate cancer cells. It might be a potential tissue and serum biomarker for predicting castration resistance in prostate cancer patients.

Methods

Novel patient-derived xenograft (PDX) castration-sensitive and -resistant models were established and gene expression patterns were comprehensively compared. The function of a gene highly expressed in the castration-resistant models was evaluated by its overexpression in LNCaP prostate cancer cells. Protein expression in the tumors and serum of patients was examined by immunohistochemistry and ELISA, and correlations with castration resistance were analyzed.

Results

Expression of the α2 chain of interleukin-13 receptor (IL13Rα2) was higher in castration-resistant PDX tumors. LNCaP cells overexpressing IL13Rα2 acquired castration resistance in vitro and in vivo. In tissue samples, IL13Rα2 expression levels were significantly associated with castration-resistant progression (p < 0.05). In serum samples, IL13Rα2 levels could be measured in 5 of 28 (18%) castration-resistant prostate cancer patients.

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