Chen Bei Jun, Byrne Frances L, Takenaka Konii, Modesitt Susan C, Olzomer Ellen M, Mills James D, Farrell Rhonda, Hoehn Kyle L, Janitz Michael
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
Division of Gynecologic Oncology, Obstetrics and Gynecology Department, University of Virginia Health System, Charlottesville, VA 22908, USA.
Gynecol Oncol. 2017 Dec;147(3):654-662. doi: 10.1016/j.ygyno.2017.10.006. Epub 2017 Oct 17.
Endometrial cancer is the most common gynecological malignancy in the developed world. It is the fifth most common cancer and accounts for 4.8% of all cancers in women. Long intergenic non-coding RNAs (lincRNAs), a subclass of long non-coding RNAs, are pervasively transcribed throughout the human genome.
LincRNA expression patterns in endometrial cancer compared to normal healthy tissue are poorly characterised. In this study, the lincRNA transcriptome of endometrial cancers and adjacent normal endometrium from the same patients was sequenced and compared with transcriptomes of other gynaecologic malignancies including ovarian and cervical cancers.
RNA was isolated from malignant and adjacent non-affected endometrial tissue from 6 patients with low grade and stage Type I endometrial cancer. Subsequently, Illumina paired-end RNA sequencing was performed, followed by bioinformatics analysis, to determine differential transcriptome expression patterns.
LINC00958 was upregulated in all three cancers, and four lincRNAs including LINC01480, LINC00645, LINC00891 and LINC00702 demonstrated exquisite specificity for malignant endometrium compared to normal endometrium while also distinguishing endometrial cancer from ovarian and cervical cancers. Furthermore, LINC01480 has features required to express a micropeptide.
The lincRNAs, characterised in this study, represent high priority genes to be tested for functional significance in the pathogenesis and/or progression of endometrial cancer. Furthermore, lincRNAs have potential to be released into the bloodstream and therefore the four lincRNAs identified here may represent biomarkers for early detection of endometrial cancer without biopsy.
子宫内膜癌是发达国家最常见的妇科恶性肿瘤。它是第五大常见癌症，占女性所有癌症的4.8%。长链基因间非编码RNA（lincRNA）是长链非编码RNA的一个亚类，在整个人类基因组中广泛转录。
与正常健康组织相比，子宫内膜癌中lincRNA的表达模式特征尚不明确。在本研究中，对同一患者的子宫内膜癌及相邻正常子宫内膜的lincRNA转录组进行测序，并与包括卵巢癌和宫颈癌在内的其他妇科恶性肿瘤的转录组进行比较。
从6例低级别I期子宫内膜癌患者的恶性及相邻未受影响的子宫内膜组织中分离RNA。随后进行Illumina双端RNA测序，接着进行生物信息学分析，以确定差异转录组表达模式。
LINC00958在所有三种癌症中均上调，包括LINC01480、LINC00645、LINC00891和LINC00702在内的四种lincRNA与正常子宫内膜相比，对恶性子宫内膜表现出高度特异性，同时也能将子宫内膜癌与卵巢癌和宫颈癌区分开来。此外，LINC01480具有表达微肽所需的特征。
本研究中鉴定的lincRNA是在子宫内膜癌发病机制和/或进展中进行功能意义测试的高度优先基因。此外，lincRNA有可能释放到血液中，因此这里鉴定的四种lincRNA可能代表无需活检即可早期检测子宫内膜癌的生物标志物。
