The association of human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) expression with gastric cancer prognosis
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Masataka Shimonosono1, Takaaki Arigami2, Shigehiro Yanagita1, Daisuke Matsushita1, Yasuto Uchikado1, Yuko Kijima1, Hiroshi Kurahara1, Yoshiaki Kita1, Shinichiro Mori1, Ken Sasaki1, Itaru Omoto1, Kosei Maemura1, Yoshikazu Uenosono1, Sumiya Ishigami1 and Shoji Natsugoe1,2
1Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
2Department of Onco-Biological Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Takaaki Arigami, email: [email protected]
Keywords: human endogenous retrovirus-H long terminal repeat-associating protein 2; quantitative reverse transcription-polymerase chain reaction; peripheral blood; prognostic marker; gastric cancer
Received: March 06, 2018 Accepted: April 05, 2018 Published: April 24, 2018
Currently, immune checkpoint blockade against members of the B7/CD28 family is being used as a new molecular-targeted therapy, in patients with unresectable advanced or recurrent gastric cancer. Although human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a novel molecule of the B7/CD28 family, the clinical impact of its expression remains uncertain in gastric cancer. Consequently, we examined HHLA2 expression in blood specimens from patients with gastric cancer, and investigated the relationship between its expression and clinicopathological factors to assess its potential power as a prognostic blood predictor. Untreated peripheral blood specimens were obtained from 111 patients with gastric cancer and 20 healthy volunteers. HHLA2 mRNA expression levels were determined using quantitative RT-PCR assay. Blood specimens obtained from patients with gastric cancer had significantly lower copies of HHLA2 mRNA than those obtained from healthy volunteers (P < 0.0001). Furthermore, HHLA2 expression was significantly correlated with the depth of tumor invasion (P = 0.0331), distant metastasis (P < 0.0001), and stage of disease (P = 0.0032). The 5-year survival rate was significantly higher in patients with high HHLA2 expression compared with the patients with low expression (P = 0.0001). These findings demonstrate that assessment of HHLA2 expression levels in the blood could be utilized to predict tumor aggressiveness in patients with gastric cancer.
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