Wang Xinmei, Li Mingyue, Yin Yingchun, Li Liang, Tao Yuqian, Chen Dengguo, Li Jianzhao, Han Hongmei, Hou Zhenbo, Zhang Baohua, Wang Xinyun, Ding Yu, Cui Haiyan, Zhang Hengming
Department of Pathology, The Central Hospital of Zibo, Zibo, Shandong 255036, P.R. China.
Department of Neurology, The First Affiliated Hospital of Zhongshan University, Guangzhou, Guangdong 510080, P.R. China.
Int J Mol Med. 2015 Jan;35(1):39-50. doi: 10.3892/ijmm.2014.1973. Epub 2014 Oct 20.
Breast cancer (BC) is a leading cause of cancer-related mortality in females and is recognized as a molecularly heterogeneous disease. Previous studies have suggested that alternative messenger RNA (mRNA) processing, particularly alternative polyadenylation [poly(A)] (APA), can be a powerful molecular biomarker with prognostic potential. Therefore, in the present study, we profiled APA sites in the luminal B subtype of BC by sequencing APA sites (SAPAS) method, in order to assess the relation of these APA site-switching events to the recognized molecular subtypes of BC, and to discover novel candidate genes and pathways in BC. Through comprehensive analysis, the trend of APA site-switching events in the 3' untranslated regions (3'UTRs) in the luminal B subtype of BC were found to be the same as that in MCF7 cell lines. Among the genes involved in the events, a significantly greater number of genes was found with shortened 3'UTRs in the samples, which were samples of primary cancer with relatively low proliferation. These findings may provide novel information for the clinical diagnosis and prognosis on a molecular level. Several potential biomarkers with significantly differential tandem 3'UTRs and expression were found and validated. The related biological progresses and pathways involved were partly confirmed by other studies. In conclusion, this study provides new insight into the diagnosis and prognosis of BC from the APA site profile aspect.
乳腺癌（BC）是女性癌症相关死亡的主要原因，并且被认为是一种分子异质性疾病。先前的研究表明，替代性信使核糖核酸（mRNA）加工，尤其是替代性聚腺苷酸化[poly(A)]（APA），可能是一种具有预后潜力的强大分子生物标志物。因此，在本研究中，我们通过测序APA位点（SAPAS）方法对BC的管腔B亚型中的APA位点进行了分析，以评估这些APA位点转换事件与BC公认分子亚型之间的关系，并发现BC中的新候选基因和途径。通过综合分析，发现BC管腔B亚型的3'非翻译区（3'UTRs）中APA位点转换事件的趋势与MCF7细胞系中的相同。在参与这些事件的基因中，发现样本中3'UTRs缩短的基因数量明显更多，这些样本是增殖相对较低的原发性癌样本。这些发现可能在分子水平上为临床诊断和预后提供新信息。发现并验证了几种具有显著差异串联3'UTRs和表达的潜在生物标志物。其他研究部分证实了所涉及的相关生物学进程和途径。总之，本研究从APA位点谱方面为BC的诊断和预后提供了新见解。
