Open Access

Identification of tumor microenvironment‑associated immunological genes as potent prognostic markers in the cancer genome analysis project HOPE

  • Authors:
    • Ryota Kondou
    • Yasuto Akiyama
    • Akira Iizuka
    • Haruo Miyata
    • Chie Maeda
    • Akari Kanematsu
    • Kyoko Watanabe
    • Tadashi Ashizawa
    • Takeshi Nagashima
    • Kenichi Urakami
    • Yuji Shimoda
    • Keiichi Ohshima
    • Akio Shiomi
    • Yasuhisa Ohde
    • Masanori Terashima
    • Katsuhiko Uesaka
    • Tetsuro Onitsuka
    • Seiichiro Nishimura
    • Yasuyuki Hirashima
    • Nakamasa Hayashi
    • Yoshio Kiyohara
    • Yasuhiro Tsubosa
    • Hirohisa Katagiri
    • Masashi Niwakawa
    • Kaoru Takahashi
    • Hiroya Kashiwagi
    • Masahiro Nakagawa
    • Yuji Ishida
    • Takashi Sugino
    • Akifumi Notsu
    • Keita Mori
    • Mitsuru Takahashi
    • Hirotsugu Kenmotsu
    • Ken Yamaguchi
  • View Affiliations

  • Published online on: September 13, 2021     https://doi.org/10.3892/mco.2021.2395
  • Article Number: 232
  • Copyright: © Kondou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Project High‑tech Omics‑based Patient Evaluation (HOPE), which used whole‑exome sequencing and gene expression profiling, was launched in 2014. A total of ~2,000 patients were enrolled until March 2016, and the survival time was observed up to July 2019. In our previous study, a tumor microenvironment immune type classification based on the expression levels of the programmed death‑ligand 1 (PD‑L1) and CD8B genes was performed based on four types: A, adaptive immune resistance; B, intrinsic induction; C, immunological ignorance; and D, tolerance. Type A (PD‑L1+ and CD8B+) exhibited upregulated features of T helper 1 antitumor responses. In the present study, survival time analysis at 5 years revealed that patients in type A had a better prognosis than those in other categories [5 year survival rate (%); A (80.5) vs. B (73.9), C (73.4) and D (72.6), P=0.0005]. Based on the expression data of 293 immune response‑associated genes, 62 specific genes were upregulated in the type A group. Among these genes, 18 specific genes, such as activated effector T‑cell markers (CD8/CD40LG/GZMB), effector memory T‑cell markers (PD‑1/CD27/ICOS), chemokine markers (CXCL9/CXCL10) and activated dendritic cell markers (CD80/CD274/SLAMF1), were significantly associated with a good prognosis using overall survival time analysis. Finally, multivariate Cox proportional hazard regression analyses of overall survival demonstrated that four genes (GZMB, HAVCR2, CXCL9 and CD40LG) were independent prognostic markers, and GZMB, CXCL9 and CD40LG may contribute to the survival benefit of patients in the immune type A group.
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November-2021
Volume 15 Issue 5

Print ISSN: 2049-9450
Online ISSN:2049-9469

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Copy and paste a formatted citation
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Spandidos Publications style
Kondou R, Akiyama Y, Iizuka A, Miyata H, Maeda C, Kanematsu A, Watanabe K, Ashizawa T, Nagashima T, Urakami K, Urakami K, et al: Identification of tumor microenvironment‑associated immunological genes as potent prognostic markers in the cancer genome analysis project HOPE. Mol Clin Oncol 15: 232, 2021
APA
Kondou, R., Akiyama, Y., Iizuka, A., Miyata, H., Maeda, C., Kanematsu, A. ... Yamaguchi, K. (2021). Identification of tumor microenvironment‑associated immunological genes as potent prognostic markers in the cancer genome analysis project HOPE. Molecular and Clinical Oncology, 15, 232. https://doi.org/10.3892/mco.2021.2395
MLA
Kondou, R., Akiyama, Y., Iizuka, A., Miyata, H., Maeda, C., Kanematsu, A., Watanabe, K., Ashizawa, T., Nagashima, T., Urakami, K., Shimoda, Y., Ohshima, K., Shiomi, A., Ohde, Y., Terashima, M., Uesaka, K., Onitsuka, T., Nishimura, S., Hirashima, Y., Hayashi, N., Kiyohara, Y., Tsubosa, Y., Katagiri, H., Niwakawa, M., Takahashi, K., Kashiwagi, H., Nakagawa, M., Ishida, Y., Sugino, T., Notsu, A., Mori, K., Takahashi, M., Kenmotsu, H., Yamaguchi, K."Identification of tumor microenvironment‑associated immunological genes as potent prognostic markers in the cancer genome analysis project HOPE". Molecular and Clinical Oncology 15.5 (2021): 232.
Chicago
Kondou, R., Akiyama, Y., Iizuka, A., Miyata, H., Maeda, C., Kanematsu, A., Watanabe, K., Ashizawa, T., Nagashima, T., Urakami, K., Shimoda, Y., Ohshima, K., Shiomi, A., Ohde, Y., Terashima, M., Uesaka, K., Onitsuka, T., Nishimura, S., Hirashima, Y., Hayashi, N., Kiyohara, Y., Tsubosa, Y., Katagiri, H., Niwakawa, M., Takahashi, K., Kashiwagi, H., Nakagawa, M., Ishida, Y., Sugino, T., Notsu, A., Mori, K., Takahashi, M., Kenmotsu, H., Yamaguchi, K."Identification of tumor microenvironment‑associated immunological genes as potent prognostic markers in the cancer genome analysis project HOPE". Molecular and Clinical Oncology 15, no. 5 (2021): 232. https://doi.org/10.3892/mco.2021.2395