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血清前列腺特异抗原(PSA)水平以及端粒酶、血管内皮生长因子(VEGF)和葡萄糖转运蛋白1(GLUT-1)蛋白表达对前列腺癌患者根治性前列腺切除术后生化复发的预后意义

Prognostic Significance of Serum PSA Level and Telomerase, VEGF and GLUT-1 Protein Expression for the Biochemical Recurrence in Prostate Cancer Patients after Radical Prostatectomy.

作者信息

Gasinska Anna, Jaszczynski Janusz, Rychlik Urszula, Łuczynska Elżbieta, Pogodzinski Marek, Palaczynski Mikolaj

机构信息

Department of Tumour Pathology, Oncology Center, Maria Sklodowska - Curie Institute, Cracow Branch, Garncarska 11, 31-115, Cracow, Poland.

Department of Surgery, Oncology Center, Maria Sklodowska - Curie Institute, Cracow Branch, Cracow, Poland.

出版信息

Pathol Oncol Res. 2020 Apr;26(2):1049-1056. doi: 10.1007/s12253-019-00659-4. Epub 2019 Apr 15.

Abstract

The aim of the study was to evaluate prognosis for biochemical recurrence (BR) by analysing the pathological and biological characteristics of prostate cancer (PCa) after radical prostatectomy (RP). There were 130 men with clinically localized PCa in whom pretreatment serum PSA level and Ki-67, prostate specific membrane antigen (PSMA), glucose transporter-1 (GLUT-1), vascular endothelial growth factor (VEGF), microvessel density (MVD) and human telomerase reverse transcriptase (hTERT) proteins expression, based on number of immunohistochemically positive cells (labelling index), were retrospectively studied. In order to assess the prognostic significance of analysed variables in univariate and multivariate Cox analysis, patients were dichotomized based on cut-off points chosen by receiver operating characteristic (ROC) curves. There were 83 males (63.8%) at pT stage 1-2 and 47 (36.1%) at pT stage 3-4, respectively, with median (range) age of 62.8 years (49-77), and median follow-up of 78.5 months (12-148). In 42 (32.3%) men BR was found. In univariate analysis, tumour biological features: PSA ≤ 8 ng/mL (p = 0.006), Ki-67LI ≤ 12.7% (p = 0.015), VEGFLI>11.0% (p = 0.030), and hTERTLI>6.7% (p = 0.016), but not clinicopathological parameters, appeared to be positive prognosticators for BRFS. In the Cox analysis, Ki-67 lost its significance, and clinicopathological parameters appeared to be nonsignificant. The independent negative prognostic factors for BRFS were: PSA > 8.0 ng/mL, (Hazard ratio = 2.75, p = 0.003), GLUT-1 > 19.1% (HR = 2.1, p = 0.032), VEGF≤11.0% (HR = 1, p = 0.024) and hTERT≤6.7% (HR = 1, p = 0.017). High PSA level, and GLUT-1 expression and lower VEGF and nuclear hTERT expression may indicate the great role of hypoxia in BR induction in PCa.

摘要

本研究的目的是通过分析根治性前列腺切除术后前列腺癌(PCa)的病理和生物学特征来评估生化复发(BR)的预后。对130例临床局限性PCa男性患者进行回顾性研究,这些患者的术前血清PSA水平、Ki-67、前列腺特异性膜抗原(PSMA)、葡萄糖转运蛋白-1(GLUT-1)、血管内皮生长因子(VEGF)、微血管密度(MVD)和人端粒酶逆转录酶(hTERT)蛋白表达,基于免疫组化阳性细胞数量(标记指数)进行分析。为了评估单因素和多因素Cox分析中所分析变量的预后意义,根据受试者工作特征(ROC)曲线选择的截断点将患者分为两组。分别有83例(63.8%)男性处于pT 1-2期和47例(36.1%)处于pT 3-4期,年龄中位数(范围)为62.8岁(49-77岁),中位随访时间为78.5个月(12-148个月)。42例(32.3%)男性出现BR。在单因素分析中,肿瘤生物学特征:PSA≤8 ng/mL(p = 0.006)、Ki-67LI≤12.7%(p = 0.015)、VEGFLI>11.0%(p = 0.030)和hTERTLI>6.7%(p = 0.016),而非临床病理参数,似乎是BRFS的阳性预后因素。在Cox分析中,Ki-67失去了其意义,临床病理参数似乎也无意义。BRFS的独立阴性预后因素为:PSA>8.0 ng/mL(风险比=2.75,p = 0.003)、GLUT-1>19.1%(HR = 2.1,p = 0.032)、VEGF≤11.0%(HR = 1,p = 0.024)和hTERT≤6.7%(HR = 1,p = 0.017)。高PSA水平、GLUT-1表达以及较低的VEGF和核hTERT表达可能表明缺氧在PCa的BR诱导中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9c/7242245/8578c13ca8f3/12253_2019_659_Fig1_HTML.jpg

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