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

Authors
  • Kondou, Ryota1
  • Akiyama, Yasuto1
  • Iizuka, Akira1
  • Miyata, Haruo1
  • Maeda, Chie1
  • Kanematsu, Akari1
  • Watanabe, Kyoko1
  • Ashizawa, Tadashi1
  • Nagashima, Takeshi2, 3
  • Urakami, Kenichi2
  • Shimoda, Yuji2, 3
  • Ohshima, Keiichi4
  • Shiomi, Akio5
  • Ohde, Yasuhisa6
  • Terashima, Masanori7
  • Uesaka, Katsuhiko8
  • Onitsuka, Tetsuro9
  • Nishimura, Seiichiro10
  • Hirashima, Yasuyuki11
  • Hayashi, Nakamasa12
  • And 14 more
  • 1 Division of Immunotherapy, Shizuoka Cancer Center Research Institute, Shizuoka 411-8777, Japan
  • 2 Division of Cancer Diagnostics Research, Shizuoka Cancer Center Research Institute, Shizuoka 411-8777, Japan
  • 3 Special Reference Laboratory, Tokyo 191-0002, Japan
  • 4 Medical Genetics Division, Shizuoka Cancer Center Research Institute, Shizuoka 411-8777, Japan
  • 5 Division of Colon and Rectal Surgery, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan
  • 6 Division of Thoracic Surgery, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan
  • 7 Division of Gastric Surgery, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan
  • 8 Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan
  • 9 Division of Head and Neck Surgery, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan
  • 10 Division of Breast Surgery, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan
  • 11 Division of Gynecology, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan
  • 12 Division of Neurosurgery, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan
  • 13 Division of Dermatology, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan
  • 14 Division of Esophageal Surgery, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan
  • 15 Division of Orthopedic Oncology, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan
  • 16 Division of Urology, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan
  • 17 Division of Breast Oncology Center, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan
  • 18 Division of Ophthalmology, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan
  • 19 Division of Plastic and Reconstructive Surgery, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan
  • 20 Division of Pediatrics, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan
  • 21 Division of Pathology, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan
  • 22 Clinical Trial Coordination Office, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan
  • 23 Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan
  • 24 Shizuoka Cancer Center, Shizuoka 411-8777, Japan
Type
Published Article
Journal
Molecular and Clinical Oncology
Publisher
D.A. Spandidos
Publication Date
Sep 13, 2021
Volume
15
Issue
5
Identifiers
DOI: 10.3892/mco.2021.2395
PMCID: PMC8461598
Source
PubMed Central
Keywords
Disciplines
  • Articles
License
Unknown

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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