NURR1 Is Differentially Expressed in Breast Cancer According to Patient Racial Identity and Tumor Subtype.
NURR1 Is Differentially Expressed in Breast Cancer According to Patient Racial Identity and Tumor Subtype.
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DOI：
10.3390/biomedinformatics2040045
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发表时间：
2022-12
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乳腺癌（BCa）仍然是美国女性癌症相关死亡的第二大常见原因。尽管雌激素受体（ER）表达通常被认为是一个有利的预后指标，但很大一部分ER（+）患者仍然会经历原发性或获得性内分泌抵抗。以前，我们已经表明，孤儿核受体BR1R1表达的损失与乳腺上皮的肿瘤转化和较短的无复发生存期（RFS）在全身治疗的乳腺癌（BCa）患者。在此，我们进一步确定了BCa中BCR1的预后价值，以及其在黑人和白色女性BCa患者中的差异表达。我们使用癌症基因组图谱（TGCA）评估了BCa患者中BCR1 mRNA的表达，并比较了基底样癌和管腔A型乳腺癌亚型的发生率。表达水平根据患者的种族身份进一步分层。我们接下来评估了在接受内分泌治疗的患者中，CD4R1表达与DX型肿瘤预后标志物的相关性，以及CD4R1表达与无复发生存率的相关性。我们的研究表明，CD3R1 mRNA表达与管腔A和基底细胞样癌BCa差异相关，并且预测无复发生存率差，证实了我们先前使用微阵列数据的研究中观察到的类似趋势。NURR 1表达与雌激素反应性相关的Oncotype DX生物标志物的表达正相关，而与细胞增殖相关的生物标志物负相关。此外，我们还观察到，在接受内分泌治疗的患者中，CDR1表达与5年无复发生存率呈正相关。有趣的是，我们发现，与具有相同亚型的白色女性相比，在具有管腔A BCa的黑人女性中，BR1表达被抑制。乳腺癌（BCa）是女性癌症死亡的主要原因之一。大多数乳腺癌是雌激素受体阳性ER（+），最初对内分泌治疗反应良好。然而，一些ER（+）BCa患者对内分泌治疗无反应，导致生存结局较差。分析癌症基因组图谱数据集，我们发现ER（+）BCa患者的ER R1基因低表达对治疗的反应较差。与其他人群相比，这种低ER（+）BCa表达主要见于黑人患者，导致ER（+）BCa的差异。ER R1表达可作为一种预后生物标志物，用于识别可能受益于早期积极治疗策略的ER（+）BCa患者。
Breast carcinoma (BCa) remains the second most common cause of cancer-related death among American women. Whereas estrogen receptor (ER) expression is typically regarded as a favorable prognostic indicator, a significant proportion of ER(+) patients still experience either de novo or acquired endocrine resistance. Previously, we have shown that the loss of orphan nuclear receptor NURR1 expression is associated with neoplastic transformation of the breast epithelium and shorter relapse-free survival (RFS) among systemically treated breast cancer (BCa) patients. Here, we further ascertain the prognostic value of NURR1 in BCa, and its differential expression among Black and White female BCa patients. We assessed the expression of NURR1 mRNA in BCa patients using the Cancer Genome Atlas (TGCA) and compared the occurrence of basal-like cancer and luminal A breast cancer subtypes. Expression levels were further stratified according to racial identity of the patient. We next assessed the correlation of NURR1 expression with Oncotype DX prognostic markers, and the association of NURR1 expression with relapse free survival in patients treated with endocrine therapy. Our study shows that NURR1 mRNA expression is differentially correlated with luminal A vs. basal-like cancer BCa and is predictive of poor relapse-free survival, confirming a similar trend observed in our previous studies using microarray data. NURR1 expression was positively correlated with expression of Oncotype DX biomarkers associated with estrogen responsiveness, while being inversely correlated with biomarkers associated with cell proliferation. Furthermore, we observed that NURR1 expression was positively associated with greater relapse-free survival at 5 years among patients treated with endocrine therapy. Interestingly, we found that among Black women with luminal A BCa, NURR1 expression was repressed in comparison to White women with the same subtype. Breast cancer (BCa) is one of the leading causes of cancer death in women. The majority of breast cancers are estrogen receptor positive ER(+) and initially respond well to endocrine therapy. However, some patients with ER(+) BCa do not respond to endocrine therapy resulting in poor survival outcomes. Analyzing the Cancer Genome Atlas datasets, we found that patients with low expression of NURR1 gene with ER(+) BCa have poor survivorship in response to treatment. This low NURR1 expression is predominantly found in Black patients compared to other population groups leading to the disparity in ER(+) BCa. NURR1 expression can serve as a prognostic biomarker in identifying ER(+) BCa patients that may benefit from early, aggressive treatment strategies.