Intrinsic Subtypes and Gene Expression Profiles in Primary and Metastatic Breast Cancer.
Intrinsic Subtypes and Gene Expression Profiles in Primary and Metastatic Breast Cancer.
复制标题
DOI：
10.1158/0008-5472.can-16-2717
复制
发表时间：
2017-05-01
期刊：
影响因子：
11.2
通讯作者：
Prat A
中科院分区：
文献类型：
--
作者：
Cejalvo JM;Martínez de Dueñas E;Galván P;García-Recio S;Burgués Gasión O;Paré L;Antolín S;Martinello R;Blancas I;Adamo B;Guerrero-Zotano Á;Muñoz M;Nucíforo P;Vidal M;Pérez RM;Chacón López-Muniz JI;Caballero R;Peg V;Carrasco E;Rojo F;Perou CM;Cortés J;Adamo V;Albanell J;Gomis RR;Lluch A;Prat A
发生在乳腺癌转移进展过程中的生物学变化仍然没有完全的特征。在这项研究中，我们比较了123对来自乳腺癌患者的原发和转移组织中固有的分子亚型和基因表达。使用PAM50型分类器鉴定固有亚型，χ2检验确定变量分布的差异。基底细胞样瘤、HER2-E瘤、B腔瘤和A腔瘤的亚型转换率分别为0%、23.1%、30.0%和55.3%。40.2%的A腔肿瘤转变为B腔肿瘤，14.3%的A、B腔肿瘤转变为HER2-E肿瘤。我们确定了47个在转移性疾病和原发疾病中差异表达的基因。转移性肿瘤中与增殖和迁移相关的基因丰富，而腔相关基因减少。当分析转移组织而不是原发组织时，增殖相关基因的表达在预测转移性疾病(OSMET)的总体生存方面更好。相比之下，与转移组织相比，基底样基因表达特征在预测原发疾病中的奥斯美特方面更好。我们观察了肿瘤复发时间与转移性疾病与原发疾病的增殖、管腔B或HER2-E信号改变的程度之间的相关性。虽然固有亚型在转移过程中基本保持不变，但在转移过程中，鲁米那/HER2阴性肿瘤获得了管腔B或HER2-E特征，这可能反映了肿瘤的进化或获得了雌激素的独立性。总体而言，我们的分析揭示了按癌症亚型和组织类型分层基因表达的价值，为临床医生提供了更精细的工具来评估预后和治疗。
Biological changes that occur during metastatic progression of breast cancer are still incompletely characterized. In this study, we compared intrinsic molecular subtypes and gene expression in 123 paired primary and metastatic tissues from breast cancer patients. Intrinsic subtype was identified using a PAM50 classifier and χ2 tests determined the differences in variable distribution. The rate of subtype conversion was 0% in basal-like tumors, 23.1% in HER2-enriched (HER2-E) tumors, 30.0% in luminal B tumors, and 55.3% in luminal A tumors. In 40.2% of cases, luminal A tumors converted to luminal B tumors, whereas in 14.3% of cases luminal A and B tumors converted to HER2-E tumors. We identified 47 genes that were expressed differentially in metastatic versus primary disease. Metastatic tumors were enriched for proliferation-related and migration-related genes and diminished for luminal-related genes. Expression of proliferation-related genes were better at predicting overall survival in metastatic disease (OSmet) when analyzed in metastatic tissue rather than primary tissue. In contrast, a basal-like gene expression signature was better at predicting OSmet in primary disease compared with metastatic tissue. We observed correlations between time to tumor relapse and the magnitude of changes of proliferation, luminal B, or HER2-E signatures in metastatic versus primary disease. Although the intrinsic subtype was largely maintained during metastatic progression, luminal/HER2-negative tumors acquired a luminal B or HER2-E profile during metastatic progression, likely reflecting tumor evolution or acquisition of estrogen independence. Overall, our analysis revealed the value of stratifying gene expression by both cancer subtype and tissue type, providing clinicians more refined tools to evaluate prognosis and treatment.