Prognostic value of MAGEA4 in primary lung cancer depends on subcellular localization and p53 status

Aki Fujiwara-Kuroda, Tatsuya Kato, Takehiro Abiko, Takahiro Tsuchikawa, Noriaki Kyogoku, Masaomi Ichinokawa, Kimitaka Tanaka, Takehiro Noji, Yasuhiro Hida, Kichizo Kaga, Yoshiro Matsui, Hiroaki Ikeda, Shinichi Kageyama, Hiroshi Shiku, Satoshi Hirano

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Melanoma antigen family A4 (MAGEA4), a cancer/testis antigen, is overexpressed and is thus an immunotherapy target in various malignant tumors, including non-small cell lung cancer. However, whether MAGEA4 induces or inhibits the apoptosis of lung cancer cells remains controversial, as is its prognostic significance, particularly since there is no reliable method with which to detect MAGEA4 specifically. In this study, we optimized assay conditions to detect MAGEA4 based on cells transiently transfected with MAGEA genes, and found that MAGEA4 was expressed in four of eight non-small cell lung cancer cell lines, and in 25.4% of clinical lung cancer specimens. We also found that MAGEA4 overexpression decreased apoptosis, as measured by the levels of cleaved caspase-3 in stably transfected 293F cells. Notably, patients with nuclear MAGEA4, but not p53 expression exhibited a significantly poorer survival than those expressing both nuclear MAGEA4 and p53. Indeed, multivariate analysis identified nuclear MAGEA4 as an independent prognostic factor (P=0.0042), albeit only in the absence of p53. In this study, to the best of our knowledge, we are the first to demonstrate that the function and prognostic value of MAGEA4 depends on its subcellular localization and on the p53 status.

Original languageEnglish
Pages (from-to)713-724
Number of pages12
JournalInternational journal of oncology
Volume53
Issue number2
DOIs
Publication statusPublished - 08-2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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