Prostate epithelial genes define therapy-relevant prostate cancer molecular subtype.
Prostate epithelial genes define therapy-relevant prostate cancer molecular subtype.
复制标题
DOI：
10.1038/s41391-021-00364-x
复制
发表时间：
2021-12
影响因子：
4.8
通讯作者：
Choi YD
中科院分区：
文献类型：
--
作者：
Han H;Lee HH;Choi K;Moon YJ;Heo JE;Ham WS;Jang WS;Rha KH;Cho NH;Giancotti FG;Choi YD
前列腺癌(PCA)的转录图谱显示出多维的变异性，潜在地源于起源细胞，反映在血清标记物中，最重要的是与药物敏感性有关。例如，侵袭性变异型前列腺癌(AVPC)每肿瘤负担的PSA较低，其特点是对雄激素受体信号抑制物(ARIS)产生从头抵抗。了解PCA转录的复杂性可以提供生物学洞察力和治疗指导。然而，非监督聚类分析受到潜在的混杂因素的阻碍，例如基质污染和与应力相关的材料降解。为了关注与前列腺上皮细胞相关的异质性，我们通过分析公开的批量和单细胞RNA测序数据，定义了1,629个由前列腺上皮细胞表达的基因。采用共识聚类和Ciberort去卷积方法进行类发现和比例估计分析。癌症基因组图谱前列腺癌数据集作为训练集。根据临床、病理和基因组特征以及对存活率的影响对所产生的聚类群进行分析。分析血清标志物PSA和PAP以预测转移环境中多西紫杉醇化疗的疗效。我们发现了两个腔内亚型和两个侵袭性变异亚型：腔A(脂肪来源/AR-活性/PSA-高)(30.0%)；腔S(分泌型/PAP-高)(26.0%)；AvPC-I(免疫浸润型)(14.7%)；AvPC-M(Myc-Active)(4.2%)；以及混合型(25.0%)。预计AVPC-I和AVPC-M亚型对ARI具有抵抗力，每肿瘤负荷的PSA较低。鲁米那A和AVPC-M对多西紫杉醇耐药，PSA/PAP比值较高。在多西紫杉醇化疗后，转移性前列腺癌患者的无进展生存期显著短于低比率患者(≤为20)。我们提出了四种前列腺癌亚型，它们具有不同的转录、基因组和病理特征。晚期癌症患者的PSA/PAP比率可能有助于确定哪些患者将受益于最大限度地抑制雄激素受体或早期使用抗微管药物。
Transcriptomic landscape of prostate cancer (PCa) shows multidimensional variability, potentially arising from the cell-of-origin, reflected in serum markers, and most importantly related to drug sensitivities. For example, Aggressive Variant Prostate Cancer (AVPC) presents low PSA per tumor burden, and characterized by de novo resistance to androgen receptor signaling inhibitors (ARIs). Understanding PCa transcriptomic complexity can provide biological insight and therapeutic guidance. However, unsupervised clustering analysis is hindered by potential confounding factors such as stromal contamination and stress-related material degradation. To focus on prostate epithelial cell-relevant heterogeneity, we defined 1,629 genes expressed by prostate epithelial cells by analyzing publicly available bulk and single- cell RNA sequencing data. Consensus clustering and CIBERSORT deconvolution were used for class discovery and proportion estimate analysis. The Cancer Genome Atlas Prostate Adenocarcinoma dataset served as a training set. The resulting clusters were analyzed in association with clinical, pathologic, and genomic characteristics and impact on survival. Serum markers PSA and PAP was analyzed to predict response to docetaxel chemotherapy in metastatic setting. We identified two luminal subtypes and two aggressive variant subtypes of PCa: luminal A (Adipogenic/AR-active/PSA-high) (30.0%); luminal S (Secretory/PAP-high) (26.0%); AVPC-I (Immune-infiltrative) (14.7%), AVPC-M (Myc-active) (4.2%), and mixed (25.0%). AVPC-I and AVPC-M subtypes predicted to be resistant to ARI and have low PSA per tumor burden. Luminal A and AVPC-M predicted to be resistant to docetaxel and have high PSA/PAP Ratio. Metastatic PCa patients with high PSA/PAP ratio (>20) had significantly shorter progression-free survival than those with low ratio (≤20) following docetaxel chemotherapy. We propose four prostate adenocarcinoma subtypes with distinct transcriptomic, genomic, and pathologic characteristics. PSA/PAP ratio in advanced cancer may aid in determining which patients would benefit from maximized androgen receptor inhibition or early use of antimicrotubule agents.
登录
查看更多内容
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：
158.5
作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
通讯作者：
Young, J.
影响因子：
45.3
作者：
Hugh, Judith;Hanson, John;Vogel, Charles
通讯作者：
Vogel, Charles
TP53优于其他雄激素受体生物标志物，可以预测抗性cast割前列腺癌中的阿舍酮或恩扎拉酰胺结果。
DOI：
10.1158/1078-0432.ccr-18-1943
发表时间：
2019-03-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
De Laere B;Oeyen S;Mayrhofer M;Whitington T;van Dam PJ;Van Oyen P;Ghysel C;Ampe J;Ost P;Demey W;Hoekx L;Schrijvers D;Brouwers B;Lybaert W;Everaert EG;De Maeseneer D;Strijbos M;Bols A;Fransis K;Beije N;de Kruijff IE;van Dam V;Brouwer A;Goossens D;Heyrman L;Van den Eynden GG;Rutten A;Del Favero J;Rantalainen M;Rajan P;Sleijfer S;Ullén A;Yachnin J;Grönberg H;Van Laere SJ;Lindberg J;Dirix LY
通讯作者：
Dirix LY
影响因子：
4.6
作者：
Carm, Kristina Totland;Hoff, Andreas M.;Lovf, Marthe
通讯作者：
Lovf, Marthe