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EP1035 Comprehensive miRNA sequencing of squamous cell carcinoma arising from ovarian mature teratoma
  1. K. Yoshida,
  2. A Yokoi,
  3. S Tamauchi,
  4. Y Ikeda,
  5. N Yoshikawa,
  6. K Nishino,
  7. K Niimi,
  8. S Suzuki,
  9. H Kajiyama and
  10. F Kikkawa
  1. Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan


Introduction/Background Owing to its rarity, the carcinogenesis and molecular biological characteristics of squamous cell carcinoma arising from mature teratoma (SCC-MT) remain unclear. This study aims to elucidate the molecular background of SCC-MT from the aspects of microRNA (miRNA) profiling.

Methodology Between 2003 and 2016, all the seven patients with SCC-MT were identified, and their formalin-fixed paraffin-embedded (FFPE) cancer and contralateral normal ovarian tissues were used. Moreover, 20 mature teratoma (MT) samples were also used as control. Total RNA was extracted from FFPE tissues, and small RNA libraries were prepared. Then comprehensive miRNA sequencing was performed, and data was analysed using Rstudio. Moreover, the results were validated in patient-derived xenograft (PDX) models. We extracted total RNA from fresh frozen tissues and plasma of PDX models and analysed as described above. Finally, we performed target prediction and functional annotation analysis using miRSystem.

Results Heatmap and principal component analysis revealed markedly different miRNA profiling in cancer, normal ovarian and MT tissues. While normal ovarian tissues exhibited almost similar profiles, SCC-MT tissues differed from each other. Then we narrowed down cancer-related miRNAs. Comparing paired-cancer and normal ovaries, 15 dysregulated miRNAs were identified. Moreover, we compared SCC-MT and MT statistically. As a result, two markedly upregulated miRNAs (miR-151a-3p and miR-378a-3p) and two markedly downregulated miRNAs (miR-26a-5p and miR-99a-5p) were identified. In PDX model, the four cancer-related miRNAs were also dysregulated in cancer tissue. In addition, the two upregulated miRNAs were elevated in the murine plasma when tumour tissues were enlarged. Finally, in silico analysis indicated that targets genes of these miRNAs markedly correlated with cancer-related pathways, including 'pathway in cancer' and 'cell cycle.'

Conclusion This is the first study on miRNA sequencing for SCC-MT. The study identified four cancer-related miRNAs that were related to the feature of SCC-MT.

Disclosure This study was supported by a Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research: Grant Number 17H04338, 16K15704, and 16H02616.

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