Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
J Cell Mol Med. 2022 Jul;26(14):4007-4020. doi: 10.1111/jcmm.17436. Epub 2022 Jun 12.
The discovery of early diagnosis and prognostic markers for breast cancer can significantly improve survival and reduce mortality. LSM1 is known to be involved in the general process of mRNA degradation in complexes containing LSm subunits, but the molecular and biological functions in breast cancer remain unclear. Here, the expression of LSM1 mRNA in breast cancer was estimated using The Cancer Genome Atlas (TCGA), Oncomine, TIMER and bc-GenExMiner databases. We found that functional LSM1 inactivation caused by mutations and profound deletions predicted poor prognosis in breast cancer (BRCA) patients. LSM1 was highly expressed in both BRCA tissues and cells compared to normal breast tissues/cells. High LSM1 expression is associated with poorer overall survival and disease-free survival. The association between LSM1 and immune infiltration of breast cancer was assessed by TIMER and CIBERSORT algorithms. LSM1 showed a strong correlation with various immune marker sets. Most importantly, pharmacogenetic analysis of BRCA cell lines revealed that LSM1 inactivation was associated with increased sensitivity to refametinib and trametinib. However, both drugs could mimic the effects of LSM1 inhibition and their drug sensitivity was associated with MEK molecules. Therefore, we investigated the clinical application of LSM1 to provide a basis for sensitive diagnosis, prognosis and targeted treatment of breast cancer.
乳腺癌早期诊断和预后标志物的发现可以显著提高生存率并降低死亡率。LSM1 已知参与含有 LSm 亚基的复合物中 mRNA 降解的一般过程，但在乳腺癌中的分子和生物学功能仍不清楚。在这里，使用癌症基因组图谱 (TCGA)、Oncomine、TIMER 和 bc-GenExMiner 数据库估计了乳腺癌中 LSM1 mRNA 的表达。我们发现，突变和深刻缺失导致的功能性 LSM1 失活预测乳腺癌 (BRCA) 患者预后不良。与正常乳腺组织/细胞相比，LSM1 在 BRCA 组织和细胞中均高度表达。高 LSM1 表达与总生存期和无病生存期较差相关。通过 TIMER 和 CIBERSORT 算法评估了 LSM1 与乳腺癌免疫浸润的相关性。LSM1 与各种免疫标志物集表现出很强的相关性。最重要的是，BRCA 细胞系的遗传药理学分析表明，LSM1 失活与对 refametinib 和 trametinib 的敏感性增加有关。然而，这两种药物都可以模拟 LSM1 抑制的作用，并且它们的药物敏感性与 MEK 分子有关。因此，我们研究了 LSM1 的临床应用，为乳腺癌的敏感诊断、预后和靶向治疗提供了依据。
