POLQ過度表現會導致使用抗荷爾蒙療法治療轉移性前列腺癌失敗
蔣孟哲1 林源峰2 廖俊厚1 歸家豪1,2
1天主教耕莘醫院 外科部 泌尿外科 ; 輔仁大學醫學系
2台北醫學大學醫學院醫學系臨床醫學研究所
Overexpression of POLQ Promotes Antiandrogen Therapy Failure in Metastatic Castration Prostate Cancer
Meng-Zhe Jiang, Yuan-Feng Lin, Chun-Hou Liao, Chia-Hao Kuei,
Division of Urology, Department of Surgery, Cardinal Tien Hospital; School of Medicine, Fu-Jen Catholic University, Taipei, Taiwan1
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan2
Purpose: The mechanism of metastatic castration resistant prostate cancer still incompletely characterized at the molecular and biochemical levels. We investigate that the expression of POLQ is predominantly upregulated in primary tumors compared to normal tissues derived from patients with metastatic castration resistant prostate cancers (mCRPC).
Materials and Methods: We utilized public database to perform a global meta-analysis and prognostic estimation against POLQ transcript. We used RT-PCR technique to validate the gene expression of POLQ in a panel of prostate cancer cell lines. We investigated the correlation of POLQ expression with tumor growth of prostate cancers especially at mCRPC.
Results: We found that POLQ downregulation strongly correlates with unfavorable outcomes in patients with prostate cancers in a global meta-analysis using PrognoScan database. Particularly in prostate cancer, the low-level transcript of POLQ referred to a poor recurrence-free survival rate. Importantly, Kaplan-Meier analysis under the condition of recurrence-free survival probability demonstrated that patients with prostate cancers, especially mCRPC. Our preliminary results demonstrated that the expression of POLQ is predominantly upregulated in primary tumors compared to normal tissues derived from patients with CRPC. Moreover, our data showed that POLQ upregulation causally associates with tumor grades and pathologic metastatic stage and significantly predicts a poor prognosis in CRPC.
Conclusions: POLQ may be a useful biomarker for predicting antiandrogen response in prostate cancer patients who decide to receive a 2nd generation antiandrogen therapy of Taxan chemotherapy. This finding might also decline patients suffer to unnecessary medication treatments.