Differential expression of Annexin 2, SPINK1, and Hsp60 predict progression of prostate cancer through bifurcated WHO Gleason score categories in African American men.

Differential expression of Annexin 2, SPINK1, and Hsp60 predict progression of prostate cancer through bifurcated WHO Gleason score categories in African American men.
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膜联蛋白2,Spink1和Hsp60的差异表达通过非裔美国人男性的格里森评分类别来预测前列腺癌的进展。

DOI:
10.1002/pros.23537
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发表时间:
2018-08
期刊:
The Prostate
影响因子:
--
通讯作者:
Hudson TS
Hudson TS
中科院分区:
其他
文献类型:
--
作者:
Beyene DA;Naab TJ;Kanarek NF;Apprey V;Esnakula A;Khan FA;Blackman MR;Brown CA;Hudson TS

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尽管研究已经观察到几种与前列腺癌(PCa)进展相关的标志物,但尚未确定准确预测这种疾病进展的特异性标志物,即使在非洲裔美国人(AA)男性中也是如此,他们通常比其他种族群体的风险更高。本研究的主要目的是探讨三种标志物是否可以预测PCa的进展。我们研究了79例存档的人前列腺经直肠超声(TRUS)活检组织中膜联蛋白2(ANX 2)、丝氨酸肽酶抑制剂、kazal 1型(SPINK 1)/肿瘤相关胰蛋白酶抑制剂(TATI)和热休克蛋白60(Hsp 60)的蛋白表达,根据修改的世界卫生组织(WHO)分类:正常(WHO 1a)、Gleason评分(GS 6(WHO 1b)、GS 7亚组(WHO 2 = 3 + 4、WHO 3 = 4 + 3)、GS 8(WHO 4)和GS 9 -10(WHO 5)。纳入了1990年至2013年在霍华德大学诊断的41-90岁AA男性。自动染色评估每种生物标志物的表达。斯皮尔曼相关性评估了生物标志物、WHO和改良WHO GS、年龄和5年生存率之间的方向和关系。双尾t检验和ANOVA评价了生物标志物表达与WHO正常和其他GS水平的关系以及WHO GS水平之间的关系。逻辑和线性回归分析检查了生物标志物评分与WHO GS类别之间的关系。Kaplan-Meier曲线绘制生存期。ANX 2表达随着PCa的进展而单调下降,而SPINK 1/TATI和Hsp 60的表达增加,但具有更多的WHO GS特异性效应; SPINK 1/TATI在正常和GS 2-6之间不同,HSP 60在GS 7和GS 2-6之间不同。WHO GS与ANX 2表达呈显著负相关,与SPINK 1/TATI和Hsp 60表达呈正相关。在较高GS下SPINK 1/TATI高表达与ANX 2低表达一起表现出与PCa进展和存活相关的双向关系。重要的是,数据显示ANX 2和SPINK 1/TAT 1与WHO GS高度相关,并与AA男性从PrCa的一个阶段过渡到下一个阶段高度相关。未来的研究需要在birthweight和更大的人群研究中证实ANX 2和SPINK 1之间的这种动态关系,作为所有男性PCa进展的独立预测因子。
Although studies have observed several markers correlate with progression of prostate cancer (PCa), no specific markers have been identified that accurately predict the progression of this disease, even in African American (AA) men who are generally at higher risk than other ethnic groups. The primary goal of this study was to explore whether three markers could predict the progression of PCa. We investigated protein expression of Annexin 2 (ANX2), serine peptidase inhibitor, kazal type 1(SPINK1)/tumor-associated trypsin inhibitor (TATI), and heat shock protein 60 (Hsp60) in 79 archival human prostate trans-rectal ultrasound (TRUS) biopsy tissues according to a modified World Health Organization (WHO) classification: normal (WHO1a), Gleason Score (GS6 (WHO1b), GS7 subgroups (WHO2 = 3 + 4, WHO3 = 4 + 3), GS8 (WHO4), and GS9–10 (WHO5). AA men aged 41–90 diagnosed from 1990 to 2013 at Howard University were included. Automated staining assessed expression of each biomarker. Spearman correlation assessed the direction and relationship between biomarkers, WHO and modified WHO GS, age, and 5-year survival. A two-tailed t-test and ANOVA evaluated biomarkers expression in relationship to WHO normal and other GS levels, and between WHO GS levels. A logistic and linear regression analysis examined the relationship between biomarker score and WHO GS categories. Kaplan-Meier curves graphed survival. ANX2 expression decreased monotonically with the progression of PCa while expression of SPINK1/TATI and Hsp60 increased but had a more WHO GS-specific effect; SPINK1/TATI differed between normal and GS 2–6 and HSP60 differed between GS 7 and GS 2–6. WHO GS was found to be significantly and negatively associated with ANX2, and positively with SPINK1/TATI and Hsp60 expression. High SPINK1/TATI expression together with the low ANX2 expression at higher GS exhibited a bi-directional relationship that is associated with PCa progression and survival. Importantly, the data reveal that ANX2, and SPINK1/TAT1 highly associate with WHO GS and with the transition from one stage of PrCa to the next in AA men. Future research is needed in biracial and larger population studies to confirm this dynamic relationship between ANX2 and SPINK1 as independent predictors of PCa progression in all men.
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