Abstract 3073: Low copy number of mtDNA is associated with cancer stemness in ESCC

Abstract

Abstract Alterations of mitochondrial DNA (mtDNA) copy numbers in various human cancers have been studied. However, those of esophageal squamous cell carcinoma (ESCC) is still unclear. In the present study, we investigated the correlation of mtDNA copy number with clinicopathologic features, prognosis and malignant potential of ESCC. MtDNA copy numbers of resected specimen from 80 patients treated with radical esophagectomy were measured by quantitative real-time PCR analyses. Human ESCC cells, TE8 and TE11, were cultured and depletion of mtDNA content was induced by knockdown of mitochondrial transcription factor A expression or treatment with ethidium bromide. The mRNA expression, proliferation, invasion and cell cycle were investigated. The results showed that mtDNA copy number of cancerous parts was 56.0 (37.4-234.5) % of non-cancerous parts and significantly lower (p<0.05). Low mtDNA copy number in resected cancerous tissues was significantly correlated with pathological depth of tumor invasion and pathological stage (p<0.05). The patients with lower mtDNA copy number had significantly poorer 5-year overall and recurrence-free survival than higher group (p<0.01). MtDNA depleted TE8 and TE11 cells proliferated more slowly than control cells under normoxia, but proliferated at almost the same rate even under hypoxic condition. In mtDNA depleted cells, the mRNA expression of cd44 were increased, and the sphere formation abilities were enhanced and the cell cycle arrest at G0/G1 phase was induced. In conclusion, low copy number of mtDNA is associated with cancer stemness in ESCC. MtDNA copy number may be a novel therapeutic target for esophageal squamous cell carcinoma. Citation Format: Takeo Hara, Yasunori Masuike, Koji Tanaka, Tomoki Makino, Makoto Yamasaki, Yasuhiro Miyazaki, Tsuyoshi Takahashi, Yukinori Kurokawa, Hidetoshi Eguchi, Kiyokazu Nakajima, Masaki Mori, Yuichiro Doki. Low copy number of mtDNA is associated with cancer stemness in ESCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3073.