Abstract 2393: Decreased expression of 5-hydroxymethylcytosine is associated with grade of malignancy in lung cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 77; no. 13_Supplement; p. 2393
• Main Authors: Tominaga, Yoshiaki, Ito, Ken-ichi, Nakayama, Jun
• Format: Journal Article
• Language: English
• Published: 01.07.2017
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2017-2393

Abstract Purpose: The ten-eleven translocation (TET) proteins are critical regulators in epigenetic modification. It is well known that TET proteins catalyze the oxidation of 5-methylcytosine (5-mC) to generate 5-hydroxymethylcytosine (5-hmC), and 5-hmC levels reflect diverse functions of TET proteins. It has been reported that the expression of 5-hmC in cancer tissues is decreased compared with that in normal tissues in several organs. However, 5-hmC expression in lung cancer has not been fully analyzed. To examine whether or not 5-hmC was associated with phenotypes or progression of lung cancer, we evaluated 5-hmC expression in a variety of histological types of lung cancers. Materials and methods: The expression of 5-hmC was analyzed by immunohistochemistry in 109 paired specimens of lung cancer and adjacent normal tissues obtained from the patients underwent operation at Shinshu University Hospital. Eighty-nine adenocarcinomas, 17 squamous cell carcinomas, two large cell carcinomas, and one small cell carcinoma were analyzed in the study. Results: 5-hmC expression in female was significantly lower than that in male, and was lower in smokers than non-smokers. 5-hmC expression was positive in 34.1±22.0% of lung cancer tissues and 69.4±18.8% of normal tissues. The expression of 5-hmC was significantly decreased in the lung cancer tissues compared with that in the adjacent normal tissues (p<0.001). With regard to the histological types, the positive ratios of 5-hmC expression were 36.0±21.7% in adenocarcinoma, 24.0±20.3% in squamous cell carcinoma, 8.0±7.3% in large cell carcinoma, and 13.0% in small cell carcinoma. Thus, the frequency of positive expression of 5-hmC was decreased in accordance with the increase of grade of malignancy of lung cancer, and a negative correlation between 5-hmC expression and the grade of malignancy of lung cancer was observed. On the other hand, no difference of the expression of 5-mC was observed between lung cancer tissues and normal tissues. Conclusions: Our results indicate a possibility that 5-hmC may be related to carcinogenesis and progression or differentiation of lung cancer. Citation Format: Yoshiaki Tominaga, Ken-ichi Ito, Jun Nakayama. Decreased expression of 5-hydroxymethylcytosine is associated with grade of malignancy in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2393. doi:10.1158/1538-7445.AM2017-2393