Variation in Molecularly Defined Prostate Tumor Subtypes by Self-identified Race.
Variation in Molecularly Defined Prostate Tumor Subtypes by Self-identified Race.
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DOI：
10.1016/j.euros.2022.03.014
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发表时间：
2022-06
影响因子：
2.5
通讯作者：
Rebbeck, Timothy R.
中科院分区：
文献类型：
--
作者：
Kensler, Kevin H.;Awasthi, Shivanshu;Alshalalfa, Mohamed;Trock, Bruce J.;Freedland, Stephen J.;Freeman, Michael R.;You, Sungyong;Mahal, Brandon A.;Den, Robert B.;Dicker, Adam P.;Karnes, R. Jeffrey;Klein, Eric A.;Lal, Priti;Liu, Yang;Davicioni, Elai;Rayford, Walter;Yamoah, Kosj;Rebbeck, Timothy R.
我们观察到，前列腺肿瘤分子亚型的频率在黑人和白色患者之间存在差异，并且某些亚型与种族的基因组风险评分存在差异。进一步了解前列腺肿瘤的异质性，跨种族群体可能会提供见解的临床使用亚型分类。社会经济和卫生保健利用因素是美国前列腺癌（PC）死亡率差异的主要驱动因素;然而，肿瘤分子异质性也可能导致黑人男性死亡率较高。通过自我认定的种族比较PC亚型频率和基因组攻击性的差异。在Decipher基因组学资源信息数据库（GRID）中，对426名黑人和762名白色PC患者应用5种分子亚型分类器。使用χ2检验和多变量调整logistic回归模型评估不同种族的亚型频率和肿瘤基因组风险（Decipher评分>0.6）差异。四个分类器的亚型频率不同的种族。以SPOP突变、SPINK 1过表达和神经内分泌分化为特征的亚型在黑人男性中更常见。ERG和ETS融合阳性亚型在白色男性中更常见，反映管腔与基底谱系的亚型无明显差异。假设的低风险Kamoun S2亚型仅在白色男性中与较低的Decipher评分相关（异质性p = 0.01），而攻击性You PCS 1亚型仅在白色男性中与较高的Decipher评分相关（异质性p = 0.001）。Tomlins ERG+亚型与黑人男性中相对于所有其他亚型的更高Decipher评分相关，而与白色男性无关（异质性p = 0.007）。PC分子亚型的频率因自我认定的种族而异。需要进一步的研究来评估我们的观察结果是否表明自我认定的种族在肿瘤基因组进展风险方面存在差异。我们研究了五种识别前列腺肿瘤亚型的分类器，发现黑人和白色患者的亚型频率不同。进一步的研究是必要的，以评估肿瘤亚型的差异如何导致前列腺癌死亡率的差异。
We observed that the frequency of prostate tumor molecular subtypes differed between Black and White patients and some subtypes showed differential associations with a genomic risk score by race. Further understanding of prostate tumor heterogeneity across racial groups may provide insights for the clinical use of subtyping classifiers. Socioeconomic and health care utilization factors are major drivers of prostate cancer (PC) mortality disparities in the USA; however, tumor molecular heterogeneity may also contribute to the higher mortality among Black men. To compare differences in PC subtype frequency and genomic aggressiveness by self-identified race. Five molecular subtype classifiers were applied for 426 Black and 762 White PC patients in the Decipher Genomics Resource Information Database (GRID). Differences in subtype frequency and tumor genomic risk (Decipher score >0.6) by race were evaluated using χ2 tests and multivariable-adjusted logistic regression models. Subtype frequencies differed by race for four classifiers. Subtypes characterized by the presence of SPOP mutations, SPINK1 overexpression, and neuroendocrine differentiation were more common among Black men. ERG and ETS fusion-positive subtypes were more frequent among White men, with no clear differences for subtypes reflecting luminal versus basal lineage. The hypothesized low-risk Kamoun S2 subtype was associated with a lower Decipher score among White men only (p = 0.01 for heterogeneity), while the aggressive You PCS1 subtype was associated with a higher Decipher score among White men only (p = 0.001 for heterogeneity). The Tomlins ERG+ subtype was associated with a higher Decipher score relative to all other subtypes among Black men, with no association among White men (p = 0.007 for heterogeneity). The frequency of PC molecular subtypes differed by self-identified race. Additional studies are required to evaluate whether our observations suggest differences in the tumor genomic risk of progression by self-identified race. We studied five classifiers that identify subtypes of prostate tumors and found that subtypes differed in frequency between Black and White patients. Further research is warranted to evaluate how differences in tumor subtypes may contribute to disparities in prostate cancer mortality.
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影响因子：
50.3
作者：
Taylor BS;Schultz N;Hieronymus H;Gopalan A;Xiao Y;Carver BS;Arora VK;Kaushik P;Cerami E;Reva B;Antipin Y;Mitsiades N;Landers T;Dolgalev I;Major JE;Wilson M;Socci ND;Lash AE;Heguy A;Eastham JA;Scher HI;Reuter VE;Scardino PT;Sander C;Sawyers CL;Gerald WL
通讯作者：
Gerald WL
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
2.8
作者：
Magi-Galluzzi, Cristina;Tsusuki, Toyonori;Zhou, Ming
通讯作者：
Zhou, Ming
影响因子：
28.4
作者：
Dess, Robert T.;Hartman, Holly E.;Spratt, Daniel E.
通讯作者：
Spratt, Daniel E.
影响因子：
6.6
作者：
Echevarria, Michelle I.;Awasthi, Shivanshu;Yamoah, Kosj
通讯作者：
Yamoah, Kosj