Bei Jun Chen1, Frances L Byrne1, Konii Takenaka1, Susan C Modesitt2, Ellen M Olzomer1, James D Mills3, Rhonda Farrell4, Kyle L Hoehn1, Michael Janitz5. 1. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia. 2. Division of Gynecologic Oncology, Obstetrics and Gynecology Department, University of Virginia Health System, Charlottesville, VA 22908, USA. 3. Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 4. Gynecologic Oncology, Royal Hospital for Women, University of New South Wales, Sydney, NSW 2052, Australia. 5. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia; Paul-Flechsig-Institute for Brain Research, University of Leipzig, Leipzig, Germany. Electronic address: m.janitz@unsw.edu.au.
Abstract
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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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. OBJECTIVE: 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. METHODS: 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. RESULTS: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. CONCLUSIONS: 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.
Authors: Bei Jun Chen; Frances L Byrne; Konii Takenaka; Susan C Modesitt; Ellen M Olzomer; James D Mills; Rhonda Farrell; Kyle L Hoehn; Michael Janitz Journal: Oncotarget Date: 2017-12-20