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前列腺癌的调查性临床研究第八部分:在初始诊断时的催乳素激素和垂体-睾丸-前列腺轴,以及根治性前列腺切除术后患者人群的后续聚类选择。

Investigative clinical study on prostate cancer part VIII: prolactin hormone and the pituitary-testicular-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population after radical prostatectomy.

机构信息

Department of Urology, University Integrated Hospitals, Civil Major Hospital, Verona, Italy.

出版信息

Anticancer Res. 2012 Apr;32(4):1499-506.

PMID:22493393
Abstract

AIM

To evaluate the prolactin hormone (PRL) physiopathology along the pituitary testicular prostate axis at the time of initial diagnosis of prostate cancer and the subsequent cluster selection of the patient population after radical prostatectomy in relation to clinical and pathological variables.

PATIENTS AND METHODS

Ninety-two operated prostate cancer patients were retrospectively reviewed. No patient had previously received hormonal treatment. The investigated variables included PRL, follicle stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), free testosterone (FT), total prostate specific antigen (PSA), percentage of positive cores at transrectal ultrasound scan biopsy (TRUSB) (P+), biopsy Gleason score (bGS), pathology Gleason score (pGS), estimated tumor volume in relation to percentage of prostate volume (V+), overall prostate weight (Wi) and age. Empirical PRL correlations and multiple linear predictions were investigated along the pituitary testis prostate axis in the different groups of the prostate cancer population and clustered according to pT (2a/b, 3a, 3b/4) status. The patient population was classified according to the log(10) PRL/V+ ratio and clustered as follows: group A (log(10) PRL/V+ ≤1.5), B (1.5< log(10)PRL/V+ ≤2.0) and C (log(10) PRL/V+ >2.0). Simple linear regression analysis of V+ predicting PRL was computed for assessing the clustered model and analysis of variance was performed for assessing significant differences between the groups.

RESULTS

PRL was independently predicted by FSH (p=0.01), LH (p=0.008) and P+ (p=0.06) in low-stage prostate cancer (pT2a/b). Interestingly, PRL was independently predicted by LH (p=0.03) and FSH, TT, FT, PSA, bGS, pGS, V+, Wi and age (all at p=0.01) in advanced stage-disease (pT3b/4). V+ was also significantly correlated (r=0.47) and predicted by P+ (p<0.0001) in the prostate cancer population. PRL was significantly correlated and predicted by V+ when the patient population was clustered according to the log(10)PRL/V+ ratio in group A (p=0.008), B (p<0.0001) and C (p<0.0001). Moreover, the three groups had significantly different mean values of PRL (p<0.0001), PSA (p=0.007), P+ (p=0.0001), V+ (p<0.0001), Wi (p=0.03), bGS (p=0.008), pGS (p=0.003); also, groups A, B and C had significant different pGS (p=0.03), pT (p=0.0008) and pR (p=0.01) frequency distributions.

CONCLUSION

At diagnosis, in an operated prostate cancer population, PRL was significantly correlated and independently predicted along the pituitary testis prostate axis in high-stage disease; V+ was also significantly correlated and predicted by P+. Because of the high correlation and prediction of PRL by both V+ and P+, the prostate cancer population at diagnosis was clustered according to the log(10)PRL/V+ ratio into groups A, B and C that, in theory, might be models with prognostic potential and clinical applications in the prostate cancer population. However, confirmatory studies are needed.

摘要

目的

评估前列腺癌初始诊断时垂体-睾丸-前列腺轴催乳素(PRL)的生理学,并在根治性前列腺切除术后根据临床和病理变量对患者人群进行聚类选择。

方法

回顾性分析 92 例接受手术治疗的前列腺癌患者。所有患者均未接受过激素治疗。研究的变量包括 PRL、卵泡刺激素(FSH)、黄体生成素(LH)、总睾酮(TT)、游离睾酮(FT)、总前列腺特异性抗原(PSA)、经直肠超声引导前列腺活检(TRUSB)中阳性核心的百分比(P+)、活检 Gleason 评分(bGS)、病理 Gleason 评分(pGS)、与前列腺体积百分比相关的估计肿瘤体积(V+)、前列腺总重量(Wi)和年龄。根据 pT(2a/b、3a、3b/4)状态,在不同前列腺癌患者群体中对垂体-睾丸-前列腺轴进行经验性 PRL 相关性和多元线性预测,并进行聚类。根据 log(10)PRL/V+ 比值对患者人群进行分类,并聚类为:A 组(log(10)PRL/V+≤1.5)、B 组(1.5<log(10)PRL/V+≤2.0)和 C 组(log(10)PRL/V+>2.0)。为评估聚类模型,计算了 V+ 对 PRL 的简单线性回归分析,方差分析用于评估各组之间的显著差异。

结果

在低分期前列腺癌(pT2a/b)中,PRL 独立于 FSH(p=0.01)、LH(p=0.008)和 P+(p=0.06)进行预测。有趣的是,在晚期疾病(pT3b/4)中,PRL 独立于 LH(p=0.03)和 FSH、TT、FT、PSA、bGS、pGS、V+、Wi 和年龄(均为 p=0.01)进行预测。在前列腺癌患者人群中,V+ 也与 P+显著相关(r=0.47,p<0.0001)和预测。当根据 log(10)PRL/V+ 比值对患者人群进行聚类时,PRL 与 V+显著相关和预测,A 组(p=0.008)、B 组(p<0.0001)和 C 组(p<0.0001)。此外,三组的 PRL(p<0.0001)、PSA(p=0.007)、P+(p=0.0001)、V+(p<0.0001)、Wi(p=0.03)、bGS(p=0.008)、pGS(p=0.003)的平均值差异均有统计学意义;此外,A、B 和 C 组的 pGS(p=0.03)、pT(p=0.0008)和 pR(p=0.01)频率分布也有显著差异。

结论

在接受手术治疗的前列腺癌患者人群中,PRL 在高分期疾病中沿垂体-睾丸-前列腺轴显著相关并独立预测;V+也与 P+显著相关和预测。由于 PRL 与 V+和 P+均具有高相关性和预测性,因此根据 log(10)PRL/V+ 比值对前列腺癌患者人群进行聚类为 A、B 和 C 组,这些组理论上可能是具有潜在预后和临床应用价值的模型。然而,需要进一步的验证性研究。

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