Association between SPARC mRNA Expression, Prognosis and Response to Neoadjuvant Chemotherapy in Early Breast Cancer: A Pooled in-silico Analysis
Association between SPARC mRNA Expression, Prognosis and Response to Neoadjuvant Chemotherapy in Early Breast Cancer: A Pooled in-silico Analysis
复制标题
DOI：
10.1371/journal.pone.0062451
复制
发表时间：
2013-04-26
期刊：
影响因子：
3.7
通讯作者：
Sotiriou, Christos
中科院分区：
文献类型：
--
作者：
Azim, Hatem A., Jr.;Singhal, Sandeep;Sotiriou, Christos
简介：SPARC是一种重要的细胞外基质调节剂，已被认为可以改善白蛋白结合的细胞毒素的递送。然而，它在乳腺癌（BC）中的作用知之甚少。方法：我们对公开可用的数据集进行了汇总分析，其中未接受全身治疗或接受新辅助化疗的BC患者符合条件。使用PAM-50将患者划分为分子亚型。我们计算了一个SPARC模块（SPARC7），由与SPARC >.7绝对相关的基因组成。在系统治疗的队列中，我们评估了1)根据乳腺癌亚型SPARC/SPARC7的表达，2)SPARC/SPARC7与增殖、免疫和基质相关的生物学过程之间的关系，以及3)在Cox模型中所有患者和根据肿瘤大小、淋巴结状态、组织学分级和年龄调整的不同分子亚型中SPARC/SPARC7与无复发生存率之间的关系。在新辅助队列中，我们在逻辑回归模型中评估了SPARC和pCR之间的关系，并对相同的临床病理因素进行了调整。结果：948例（10个数据集）和791例（8个数据集）患者分别被纳入系统治疗组和新辅助组。SPARC高表达与肿瘤大小小、组织学分级低和发光a型肿瘤相关(均p
Introduction: SPARC is an important regulator of the extracellular matrix and has been suggested to improve delivery of albumin-bound cytotoxics. However, little is known regarding its role in breast cancer (BC).Methods: We conducted a pooled analysis of publically available datasets, in which BC patients who received no systemic therapy or received neoadjuvant chemotherapy were eligible. Patients were assigned to molecular subtypes using PAM-50. We computed a SPARC module (SPARC7), composed of genes with an absolute correlation with SPARC >0.7. In the systemically untreated cohort, we evaluated 1) expression of SPARC/SPARC7 according to breast cancer subtype, 2) association between SPARC/SPARC7 and biological processes related to proliferation, immune and stroma, and 3) association between SPARC/SPARC7 and relapse-free survival in a Cox model in all patients and in the different molecular subtypes adjusted for tumor size, nodal status, histological grade, and age. In the neoadjuvant cohort, we evaluated the association between SPARC and pCR in a logistic regression model, adjusted for the same clinicopathologic factors.Results: 948 (10 datasets), and 791 (8 datasets) patients were included in the systemically untreated and neoadjuvant cohorts, respectively. High SPARC expression was associated with small tumor size, low histological grade and luminal-A tumors (all p