miR-200 家族的联合分析及其在乳腺癌中的意义。
Combined analysis of miR-200 family and its significance for breast cancer.
机构信息
Fondazione IRCCS Casa Sollievo della Sofferenza, UO di Biostatistica, San Giovanni Rotondo, FG, Italy.
Laboratorio Di Oncologia, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013, San Giovanni Rotondo, FG, Italy.
出版信息
Sci Rep. 2021 Feb 3;11(1):2980. doi: 10.1038/s41598-021-82286-1.
While the molecular functions of miR-200 family have been deeply investigated, a role for these miRNAs as breast cancer biomarkers remains largely unexplored. In the attempt to clarify this, we profiled the miR-200 family members expression in a large cohort of breast cancer cases with a long follow-up (H-CSS cohort) and in TCGA-BRCA cohort. Overall, miR-200 family was found upregulated in breast tumors with respect to normal breast tissues while downregulated in more aggressive breast cancer molecular subtypes (i.e. Luminal B, HER2 and triple negative), consistently with their function as repressors of the epithelial-to-mesenchymal transition (EMT). In particular miR-141-3p was found differentially expressed in breast cancer molecular subtypes in both H-CSS and TCGA-BRCA cohorts, and the combined analysis of all miR-200 family members demonstrated a slight predictive accuracy on H-CSS cancer specific survival at 12 years (survival c-statistic: 0.646; 95%CI 0.538-0.754).
虽然 miR-200 家族的分子功能已经被深入研究，但这些 miRNA 作为乳腺癌生物标志物的作用在很大程度上仍未被探索。为了阐明这一点，我们在一个具有长期随访（H-CSS 队列）的大型乳腺癌病例队列和 TCGA-BRCA 队列中对 miR-200 家族成员的表达进行了分析。总体而言，与正常乳腺组织相比，miR-200 家族在乳腺癌肿瘤中上调，而在更具侵袭性的乳腺癌分子亚型（即 Luminal B、HER2 和三阴性）中下调，这与它们作为上皮-间充质转化（EMT）的抑制剂的功能一致。特别是在 H-CSS 和 TCGA-BRCA 队列中，miR-141-3p 在乳腺癌分子亚型中存在差异表达，所有 miR-200 家族成员的联合分析在 12 年时对 H-CSS 癌症特异性生存具有微弱的预测准确性（生存 c 统计量：0.646；95%CI 0.538-0.754）。
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