High mobility group A1 (HMGA1) protein and gene expression correlate with ER-negativity and poor outcomes in breast cancer.
High mobility group A1 (HMGA1) protein and gene expression correlate with ER-negativity and poor outcomes in breast cancer.
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DOI：
10.1007/s10549-019-05419-1
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发表时间：
2020-01
影响因子：
3.8
通讯作者：
Resar, Linda M. S.
中科院分区：
文献类型：
--
作者：
Gorbounov, Mikhail;Carleton, Neil M.;Asch-Kendrick, Rebecca J.;Xian, Lingling;Rooper, Lisa;Chia, Lionel;Cimino-Mathews, Ashley;Cope, Leslie;Meeker, Alan;Stearns, Vered;Veltri, Robert W.;Bae, Young Kyung;Resar, Linda M. S.
关键词：
高迁移率族A1（HMGA 1）染色质重塑蛋白是临床前乳腺癌模型中转移进展和癌症干细胞特性所必需的，尽管其在乳腺癌发生中的作用仍不清楚。为了研究HMGA 1在原发性乳腺癌中的作用，我们评估了一个大型亚洲女性队列肿瘤的免疫反应性评分（IRS）;从两个独立的西方队列中查询HMGA 1基因表达。HMGA 1 IRS由韩国妇女的乳腺肿瘤产生，作为染色强度（弱=1，中等=2，强=3）和阳性细胞百分比（<5%=0，5-30%=1，30-60%=2，>60%=3）的乘积，并分为三组：低（<3），中等（3-6），高（>6）。我们从两个大型数据库（TCGA，METABRIC）中评估了HMGA和雌激素受体（ESR 1）基因表达。从METABRIC队列中确定总生存期。在540例韩国女性原发性肿瘤中（181例ER阴性，359例ER阳性），89例（16.5%）HMGA 1 IRS <3，215例（39.8%）3-6，236例（43.7%）>6。高HMGA 1 IRS与雌激素受体（ER）阴性（χ2=12.07; P=0.002）和晚期核分级（χ2=12.83; P=0.012）相关。在两个大型西方队列中，与非恶性乳腺组织相比，HMGA 1基因在乳腺癌中过表达（P<0.0001），包括亚洲人，非洲裔美国人和高加索人亚组。HMGA 1在ER阴性肿瘤中最高，HMGA 1和ESR 1基因表达之间存在强烈的负相关性（Pearson r =-0.60，P<0.0001）。最重要的是，高HMGA 1水平预测所有乳腺癌患者的总生存率降低（P<0.0001），并进一步将ER阳性肿瘤分为预后较差的肿瘤。总之，我们的研究结果表明，HMGA 1有助于雌激素依赖性，肿瘤进展和不良结局。此外，还需要进一步的研究来确定HMGA 1是否可以作为乳腺癌患者的预后标志物和治疗靶点。
The High Mobility Group A1 (HMGA1) chromatin remodeling protein is required for metastatic progression and cancer stem cell properties in preclinical breast cancer models, although its role in breast carcinogenesis has remained unclear. To investigate HMGA1 in primary breast cancer, we evaluated immunoreactivity score (IRS) in tumors from a large cohort of Asian women; HMGA1 gene expression was queried from two independent Western cohorts. HMGA1 IRS was generated from breast tumors in Korean women as the product of staining intensity (weak=1, moderate=2, strong=3) and percent positive cells (<5%=0, 5–30%=1, 30–60%=2, >60%=3) and stratified into three groups: low (<3), intermediate (3–6), high (>6). We assessed HMGA and Estrogen Receptor (ESR1) gene expression from two large databases (TCGA, METABRIC). Overall survival was ascertained from the METABRIC cohort. Among 540 primary tumors from Korean women (181 ER-negative, 359 ER-positive), HMGA1 IRS was <3 in 89 (16.5%), 3–6 in 215 (39.8%), and >6 in 236 (43.7%). High HMGA1 IRS was associated with estrogen receptor (ER)-negativity (χ2=12.07; P=0.002) and advanced nuclear grade (χ2=12.83; P=0.012). In two large Western cohorts, the HMGA1 gene was overexpressed in breast cancers compared to non-malignant breast tissue (P<0.0001), including Asian, African American, and Caucasian subgroups. HMGA1 was highest in ER-negative tumors and there was a strong inverse correlation between HMGA1 and ESR1 gene expression (Pearson r = −0.60, P<0.0001). Most importantly, high HMGA1 predicted decreased overall survival (P<0.0001) for all women with breast cancer and further stratified ER-positive tumors into those with inferior outcomes. Together, our results suggest that HMGA1 contributes to estrogen-independence, tumor progression, and poor outcomes. Moreover, further studies are warranted to determine whether HMGA1 could serve as a prognostic marker and therapeutic target for women with breast cancer.
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影响因子：
5.4
作者：
Lee G;Veltri RW;Zhu G;Ali S;Epstein JI;Madabhushi A
通讯作者：
Madabhushi A
影响因子：
50.3
作者：
Berger AC;Korkut A;Kanchi RS;Hegde AM;Lenoir W;Liu W;Liu Y;Fan H;Shen H;Ravikumar V;Rao A;Schultz A;Li X;Sumazin P;Williams C;Mestdagh P;Gunaratne PH;Yau C;Bowlby R;Robertson AG;Tiezzi DG;Wang C;Cherniack AD;Godwin AK;Kuderer NM;Rader JS;Zuna RE;Sood AK;Lazar AJ;Ojesina AI;Adebamowo C;Adebamowo SN;Baggerly KA;Chen TW;Chiu HS;Lefever S;Liu L;MacKenzie K;Orsulic S;Roszik J;Shelley CS;Song Q;Vellano CP;Wentzensen N;Cancer Genome Atlas Research Network;Weinstein JN;Mills GB;Levine DA;Akbani R
通讯作者：
Akbani R
影响因子：
8
作者：
Dhar, A;Hu, J;Colburn, NH
通讯作者：
Colburn, NH
影响因子：
2.6
作者：
Di Cello, Francescopaolo;Dhara, Surajit;Resar, Linda
通讯作者：
Resar, Linda
影响因子：
23.9
作者：
Choudhury, Sibgat;Almendro, Vanessa;Polyak, Kornelia
通讯作者：
Polyak, Kornelia