Racial differences in the expression of inhibitors of apoptosis (IAP) proteins in extracellular vesicles (EV) from prostate cancer patients.
Racial differences in the expression of inhibitors of apoptosis (IAP) proteins in extracellular vesicles (EV) from prostate cancer patients.
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DOI：
10.1371/journal.pone.0183122
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Wall NR
中科院分区：
文献类型：
--
作者：
Khan S;Simpson J;Lynch JC;Turay D;Mirshahidi S;Gonda A;Sanchez TW;Casiano CA;Wall NR
患有前列腺癌的非洲裔美国男性通常比其他种族/民族的男性发展出更具侵袭性的肿瘤，导致这种恶性肿瘤的死亡率不成比例地高。本研究评估了非洲裔美国人和欧洲裔美国人前列腺癌男性之间血液来源的外泌体囊泡（EV）中凋亡抑制蛋白（IAP）（一种已知的癌蛋白家族）表达的差异。ExoQuick™方法用于从患有前列腺癌的非洲裔美国人（n = 41）和欧洲裔美国人（n = 31）男性的血浆和血清中以及从没有癌症诊断的对照（n = 10）中分离EV。EV制剂通过乙酰胆碱酯酶活性测定进行定量，并通过Western印迹和光密度分析评估其IAP含量。通过ELISA评估IAP存活素的循环水平。我们检测到前列腺癌患者与对照组相比循环Survivin水平显著增加（P<0.01），非洲裔美国人患者的水平最高（P<0.01）。患有前列腺癌的非洲裔美国患者的血浆（P<0.01）和血清（P<0.05）中EV的含量也显著高于欧洲裔美国患者。此外，来自患有前列腺癌的非洲裔美国患者的EV含有比来自欧洲裔美国患者的EV显著更高量的IAP Survivin（P<0.05）、XIAP（P<0.001）和cIAP-2（P<0.01）。两组患者中IAP的表达与临床病理参数之间无显著相关性。非洲裔美国前列腺癌患者EV中IAP表达增加可能影响肿瘤侵袭性，并导致该患者人群中观察到的死亡率差异。EV可以作为新型生物标志物和治疗靶点的储存库，这些生物标志物和治疗靶点可能在减少前列腺癌健康差异方面具有临床实用性。
African-American men with prostate cancer typically develop more aggressive tumors than men from other racial/ethnic groups, resulting in a disproportionately high mortality from this malignancy. This study evaluated differences in the expression of inhibitors of apoptosis proteins (IAPs), a known family of oncoproteins, in blood-derived exosomal vesicles (EV) between African-American and European-American men with prostate cancer. The ExoQuick™ method was used to isolate EV from both plasma and sera of African-American (n = 41) and European-American (n = 31) men with prostate cancer, as well as from controls with no cancer diagnosis (n = 10). EV preparations were quantified by acetylcholinesterase activity assays, and assessed for their IAP content by Western blotting and densitometric analysis. Circulating levels of the IAP Survivin were evaluated by ELISA. We detected a significant increase in the levels of circulating Survivin in prostate cancer patients compared to controls (P<0.01), with the highest levels in African-American patients (P<0.01). African-American patients with prostate cancer also contained significantly higher amounts of EVs in their plasma (P<0.01) and sera (P<0.05) than European-American patients. In addition, EVs from African-American patients with prostate cancer contained significantly higher amounts of the IAPs Survivin (P<0.05), XIAP (P<0.001), and cIAP-2 (P<0.01) than EVs from European-American patients. There was no significant correlation between expression of IAPs and clinicopathological parameters in the two patient groups. Increased expression of IAPs in EVs from African-American patients with prostate cancer may influence tumor aggressiveness and contribute to the mortality disparity observed in this patient population. EVs could serve as reservoirs of novel biomarkers and therapeutic targets that may have clinical utility in reducing prostate cancer health disparities.
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影响因子：
3.9
作者：
Myers JS;von Lersner AK;Sang QX
通讯作者：
Sang QX
DOI：
10.2147/btt.s83864
发表时间：
2015
期刊：
Biologics : targets & therapy
影响因子：
--
作者：
Khan S;Ferguson Bennit H;Asuncion Valenzuela MM;Turay D;Diaz Osterman CJ;Moyron RB;Esebanmen GE;Ashok A;Wall NR
通讯作者：
Wall NR
影响因子：
2.1
作者：
Hardiman, Gary;Savage, Stephen J.;Gattoni-Celli, Sebastiano
通讯作者：
Gattoni-Celli, Sebastiano
影响因子：
3.7
作者：
Khan S;Jutzy JM;Valenzuela MM;Turay D;Aspe JR;Ashok A;Mirshahidi S;Mercola D;Lilly MB;Wall NR
通讯作者：
Wall NR
影响因子：
4.8
作者：
Clayton, A;Turkes, A;Hallett, MB
通讯作者：
Hallett, MB