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Overexpression of MAGEA2 has a prognostic significance and is a potential therapeutic target for patients with lung cancer.

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Title: Overexpression of MAGEA2 has a prognostic significance and is a potential therapeutic target for patients with lung cancer.
Authors: Ujiie, Hideki Browse this author
Kato, Tatsuya Browse this author
Lee, Daiyoon Browse this author
Hu, Hsin-Pei Browse this author
Fujino, Kosuke Browse this author
Kaji, Mitsuhito Browse this author →KAKEN DB
Kaga, Kichizo Browse this author →KAKEN DB
Matsui, Yoshiro Browse this author →KAKEN DB
Yasufuku, Kazuhiro Browse this author →KAKEN DB
Keywords: biomarker
lung cancer
therapeutic target
Issue Date: Jun-2017
Journal Title: International journal of oncology
Volume: 50
Issue: 6
Start Page: 2154
End Page: 2170
Publisher DOI: 10.3892/ijo.2017.3984
PMID: 28498455
Abstract: Melanoma-associated antigens (MAGE) are expressed in different type of cancers including lung cancer and have been shown to be functionally related to p53 tumor suppressor gene. Little is known about the relationship between MAGE genes and p53 aberrant expression in lung cancer. The aims of this study were to observe the expression of MAGEA2, examine the role of MAGEA2 in lung cancer survival, investigate its correlation between MAGEA2 and p53, and explore its clinicopathologic significance as a prognostic marker. Quantitative reverse transcription-polymerase chain reaction was performed to detect the expression of MAGEA2 using 36 primary tumors and 31 metastatic lymph nodes from patients with lung cancer. The role of MAGEA2 in cancer cell growth and in the regulation of p53 downstream genes were examined using small interfering RNA. The expression of MAGEA2 and p53 were analyzed immunohistochemically using tissue microarray from 353 resected lung specimens. High-level expression of MAGEA2 (High-MAGEA2) was confirmed in lung tumors with high frequency. Inhibiting MAGEA2 expression effectively suppressed cancer cell growth and decreased the expression of p53 downstream target genes in vitro. In adenocarcinoma, High-MAGEA2 was strongly associated with aberrant p53 expression (P<0.001) and was associated with worse clinical outcomes (5-year OS, 87.1% in low vs. 74.1% in high, P=0.014). Aberrant p53 expression was also significant worse prognostic factor (P=0.029). Among the adenocarcinoma patients with wild-type p53, High-MAGEA2 had poorer prognosis than low-level MAGEA2 groups (5-year OS, 90.1% vs. 72.1%, P=0.037), whereas had no difference in p53 aberrant tumors. On multivariate analysis, MAGEA2 was independently associated with survival (hazard ratio; 2.12, P=0.030). In conclusion, suppression of MAGEA2 in lung cancer cells significantly reduced the growth/survival of cancer cells. High-MAGEA2 was identified as an independent prognostic factor in lung adenocarcinoma. Specific inhibition of MAGEA2 may be a promising therapeutic strategy for patients with lung cancer.
Type: article
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 氏家 秀樹

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