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目的:分析雄激素受体剪接变异体7(AR-V7)对前列腺癌激素抵抗敏感时间的预测作用。方法:将本院100例经活检穿刺证实为前列腺癌的患者纳入研究,所有患者均接受内分泌治疗,利用免疫组化方法检测前列腺癌组织AR-V7的表达情况,利用Cox模型分析患者各临床因素对前列腺癌激素抵抗敏感时间的影响,采用Kaplan-Meier法分析AR-V7对前列腺癌激素抵抗敏感时间的作用,同时利用Log-rank法对结果进行显著性检验。结果:(1)100例患者内分泌治疗过程中前列腺特异性抗原(PSA)最低值平均(1.1±0.08)μg·L-1;到达PSA最低值的时间平均(8.2±0.03)个月;PSA半衰期平均(1.2±0.4)个月。至随访结束有88例进展为去势抵抗性前列腺癌(CRPC),其激素敏感时间平均(28.5±1.8)个月。(2)AR-V7表达主要位于细胞核,仅有少数表达于细胞质中,100例前列腺癌患者中有25例患者AR-V7表达呈现阳性,75例患者表现为阴性。(3)Cox多因素分析显示PSA最低值、PSA半衰期及癌组织中AR-V7的表达量是影响激素敏感时间的因素,多因素分析结果显示PSA最低值(r=1.98,P=0.02)及AR-V7的表达量(r=2.93,P=0.003)是晚期前列腺癌患者激素敏感时间的独立预测因子。(4)AR-V7阳性患者的中位生存时间为(32±1.2)个月,ARV7阴性患者中位生存时间为(46±1.9)个月,差异有统计学意义(P<0.05)。结论:AR-V7是影响前列腺癌激素抵抗敏感时间的预测因子,其可能作为前列腺癌治疗新靶向。
OBJECTIVE: To analyze the predictive value of androgen receptor splice variant 7 (AR-V7) on the sensitivity of prostate cancer to hormone resistance. Methods: 100 cases of prostate cancer confirmed by biopsy were enrolled in this study. All patients received endocrine therapy. The expression of AR-V7 in prostate cancer tissues was detected by immunohistochemistry. The clinical data of Cox model The effect of AR-V7 on the sensitive time of hormone resistance in prostate cancer was analyzed by Kaplan-Meier method, and the result was tested by Log-rank method. Results: (1) The mean value of prostate-specific antigen (PSA) in 100 patients during endocrine therapy was (1.1 ± 0.08) μg · L-1; mean time to PSA was 8.2 ± 0.03 months; PSA half-life Average (1.2 ± 0.4) months. At the end of follow-up, 88 patients progressed to castration-resistant prostate cancer (CRPC). The hormone-sensitive time averaged (28.5 ± 1.8) months. (2) The expression of AR-V7 was mainly located in the nucleus, only a few were expressed in the cytoplasm. The expression of AR-V7 was positive in 25 out of 100 cases of prostate cancer, and 75 cases were negative. (3) Cox multivariate analysis showed that the lowest value of PSA, the half life of PSA and the expression of AR-V7 in cancer tissue were the factors influencing hormone sensitive time. Multivariate analysis showed the lowest PSA (r = 1.98, P = 0.02) and AR-V7 expression (r = 2.93, P = 0.003) was an independent predictor of hormone-sensitive time in patients with advanced prostate cancer. (4) The median survival time of AR-V7-positive patients was (32 ± 1.2) months, and the median survival time of ARV7-negative patients was (46 ± 1.9) months, with statistical significance (P <0.05). CONCLUSIONS: AR-V7 is a predictor of susceptibility to prostate cancer hormone resistance and may serve as a new target for the treatment of prostate cancer.