Folate receptor-α (FOLR1) expression and function in triple negative tumors.
Folate receptor-α (FOLR1) expression and function in triple negative tumors.
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DOI：
10.1371/journal.pone.0122209
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Perez EA
中科院分区：
文献类型：
--
作者：
Necela BM;Crozier JA;Andorfer CA;Lewis-Tuffin L;Kachergus JM;Geiger XJ;Kalari KR;Serie DJ;Sun Z;Moreno-Aspitia A;O'Shannessy DJ;Maltzman JD;McCullough AE;Pockaj BA;Cunliffe HE;Ballman KV;Thompson EA;Perez EA
叶酸受体α (FOLR1)已被确定为许多癌症的潜在预后和治疗靶点。FOLR1在乳腺肿瘤中强烈过表达与预后不良之间存在相关性，但对FOLR1在临床相关乳腺癌亚型中的分布的研究有限。为了进一步探讨这一点，我们使用来自多个患者队列的RNA-seq数据来分析FOLR1 mRNA在由雌激素受体阳性（ER+）、人表皮生长因子受体阳性（HER2+）和三阴性（TNBC）肿瘤组成的乳腺癌亚型中的分布。FOLR1在乳腺肿瘤亚型中的表达存在差异；与ER+和HER2+肿瘤相比，三阴性/基础肿瘤与FOLR1 mRNA表达升高显著相关。然而，在所有临床亚型中都观察到高水平表达FOLR1的肿瘤亚群。组织微阵列的免疫组化分析支持了这些观察结果，3+阳性肿瘤数量最多，以三阴性为代表的任何亚型的h评分最高，ER+肿瘤的h评分最低。FOLR1的表达与常见的临床病理参数如肿瘤分期和淋巴结状态无关。为了描述FOLR1过表达在三阴性癌症中的重要性，我们使用rna干扰来减少过表达三阴性细胞系中FOLR1的表达。FOLR1的缺失导致生长抑制，而FOLR1的过表达促进叶酸摄取和低叶酸条件下的生长优势。综上所述，我们的数据表明，表达高FOLR1表达的三阴性癌症患者是可能受益于靶向抗FOLR1治疗的重要患者群体。这可能对大量通常被归类为三阴性的患者特别有帮助，这些患者到目前为止没有任何有针对性的治疗选择。
Folate receptor alpha (FOLR1) has been identified as a potential prognostic and therapeutic target in a number of cancers. A correlation has been shown between intense overexpression of FOLR1 in breast tumors and poor prognosis, yet there is limited examination of the distribution of FOLR1 across clinically relevant breast cancer subtypes. To explore this further, we used RNA-seq data from multiple patient cohorts to analyze the distribution of FOLR1 mRNA across breast cancer subtypes comprised of estrogen receptor positive (ER+), human epidermal growth factor receptor positive (HER2+), and triple negative (TNBC) tumors. FOLR1 expression varied within breast tumor subtypes; triple negative/basal tumors were significantly associated with increased expression of FOLR1 mRNA, compared to ER+ and HER2+ tumors. However, subsets of high level FOLR1 expressing tumors were observed in all clinical subtypes. These observations were supported by immunohistochemical analysis of tissue microarrays, with the largest number of 3+ positive tumors and highest H-scores of any subtype represented by triple negatives, and lowest by ER+ tumors. FOLR1 expression did not correlate to common clinicopathological parameters such as tumor stage and nodal status. To delineate the importance of FOLR1 overexpression in triple negative cancers, RNA-interference was used to deplete FOLR1 in overexpressing triple negative cell breast lines. Loss of FOLR1 resulted in growth inhibition, whereas FOLR1 overexpression promoted folate uptake and growth advantage in low folate conditions. Taken together, our data suggests patients with triple negative cancers expressing high FOLR1 expression represent an important population of patients that may benefit from targeted anti-FOLR1 therapy. This may prove particularly helpful for a large number of patients who would typically be classified as triple negative and who to this point have been left without any targeted treatment options.
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DOI：
10.1093/bioinformatics/btq033
发表时间：
2010-03-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Quinlan AR;Hall IM
通讯作者：
Hall IM
影响因子：
254.7
作者：
DeSantis, Carol;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
3.6
作者：
Lin, JianMin;Spidel, Jared L.;Grasso, Luigi
通讯作者：
Grasso, Luigi
影响因子：
9.3
作者：
Maurer, Alan H.;Elsinga, Philip;Weber, Wolfgang A.
通讯作者：
Weber, Wolfgang A.
影响因子：
12.3
作者：
Langmead B;Trapnell C;Pop M;Salzberg SL
通讯作者：
Salzberg SL