CD26 overexpression is associated with prolonged survival and enhanced chemosensitivity in malignant pleural mesothelioma

Keisuke Aoe, Vishwa Jeet Amatya, Nobukazu Fujimoto, Kei Ohnuma, Osamu Hosono, Akio Hiraki, Masanori Fujii, Taketo Yamada, Nam H. Dang, Yukio Takeshima, Kouki Inai, Takumi Kishimoto, Chikao Morimoto

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43 Citations (Scopus)

Abstract

Purpose: Malignant pleural mesothelioma (MPM) is an aggressive and therapy-resistant neoplasm arising from the pleural mesothelial cells, without established indicators to predict responsiveness to chemotherapy. Experimental Design: Our study involving 79 MPM patients showed that 73.4% of MPM expressed CD26 on cell membrane. Results: The majority of epithelioid and biphasic types of MPM expressed CD26 on the cell membrane, whereas the sarcomatoid type showed a lack of CD26 surface expression. Although the sarcomatoid type was associated with poor prognosis (P < 0.0001), no significant relationship between CD26 expression and survival was observed. On the contrary, there was a trend for an association between response rate to chemotherapy and CD26 expression (P = 0.053), with a higher level of CD26 expression more likely to be linked to better response to chemotherapy. Moreover, CD26 expression was a significant factor associated with improved survival in patients who received chemotherapy [median survival time (MST), 18.6 vs. 10.7 months, P = 0.0083]. Furthermore, CD26 expression was significantly associated with better prognosis in patients receiving non-pemetrexed-containing regimens (MST, 14.2 vs. 7.4 months, P = 0.0042), whereas there was no significant association between CD26 expression and survival time for patients receiving pemetrexed-containing regimens. Our in vitro and microarray studies showed that mesothelioma cells expressing high CD26 displayed high proliferative activity, and CD26 expression was closely linked to cell-cycle regulation, apoptosis, and chemotherapy resistance. Conclusions: Our results strongly suggest that CD26 is a clinically significant biomarker for predicting response to chemotherapy for MPM.

Original languageEnglish
Pages (from-to)1447-1456
Number of pages10
JournalClinical Cancer Research
Volume18
Issue number5
DOIs
Publication statusPublished - 2012 Mar 1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Aoe, K., Amatya, V. J., Fujimoto, N., Ohnuma, K., Hosono, O., Hiraki, A., Fujii, M., Yamada, T., Dang, N. H., Takeshima, Y., Inai, K., Kishimoto, T., & Morimoto, C. (2012). CD26 overexpression is associated with prolonged survival and enhanced chemosensitivity in malignant pleural mesothelioma. Clinical Cancer Research, 18(5), 1447-1456. https://doi.org/10.1158/1078-0432.CCR-11-1990