Splicing Factor Transcript Abundance in Saliva as a Diagnostic Tool for Breast Cancer
Splicing Factor Transcript Abundance in Saliva as a Diagnostic Tool for Breast Cancer
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DOI：
10.3390/genes11080880
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发表时间：
2020-08-01
期刊：
影响因子：
3.5
通讯作者：
Salton, Maayan
中科院分区：
文献类型：
--
作者：
Bentata, Mercedes;Morgenstern, Guy;Salton, Maayan
乳腺癌是美国60岁以上女性的第二大死因。建议对50岁以上的女性进行乳房X光检查；然而，22%的乳腺癌病例是在这一年龄以下的女性中诊断出来的。我们着手开发一种基于从唾液中检测出无细胞RNA的测试。为此，我们对10名女性的RNA进行了测序。在鉴定的1254个转录本中，基因被丰富，并带有可供选择的前mRNA剪接的注释。Pre-mRNA剪接是一个严格调控的过程，它在癌细胞中的错误调控促进了癌症驱动亚型的形成。出于这些原因，我们选择专注于剪接因子作为乳腺癌早期检测的生物标记物。我们发现，剪接因子的水平对于每个女性来说都是独一无二的，并且在同一个女性的不同时间点上是一致的。接下来，我们提取了36名健康受试者和31名乳腺癌患者的RNA。记录这些样本中7种剪接因子的基因表达水平，发现这些因子的组合在两组中不同(p值=0.005)。我们的结果表明，乳腺癌患者唾液中剪接因子mRNA的丰度不同。
Breast cancer is the second leading cause of death in women above 60 years in the US. Screening mammography is recommended for women above 50 years; however, 22% of breast cancer cases are diagnosed in women below this age. We set out to develop a test based on the detection of cell-free RNA from saliva. To this end, we sequenced RNA from a pool of ten women. The 1254 transcripts identified were enriched for genes with an annotation of alternative pre-mRNA splicing. Pre-mRNA splicing is a tightly regulated process and its misregulation in cancer cells promotes the formation of cancer-driving isoforms. For these reasons, we chose to focus on splicing factors as biomarkers for the early detection of breast cancer. We found that the level of the splicing factors is unique to each woman and consistent in the same woman at different time points. Next, we extracted RNA from 36 healthy subjects and 31 breast cancer patients. Recording the mRNA level of seven splicing factors in these samples demonstrated that the combination of all these factors is different in the two groups (pvalue = 0.005). Our results demonstrate a differential abundance of splicing factor mRNA in the saliva of breast cancer patients.