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12‐Chemokine signature, a predictor of tumor recurrence in colorectal cancer
Author(s) -
Tokunaga Ryuma,
Nakagawa Shigeki,
Sakamoto Yasuo,
Nakamura Kenichi,
Naseem Madiha,
Izumi Daisuke,
Kosumi Keisuke,
Taki Katsunobu,
Higashi Takaaki,
Miyata Tatsunori,
Miyamoto Yuji,
Yoshida Naoya,
Baba Hideo,
Lenz HeinzJosef
Publication year - 2020
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32982
Subject(s) - chemokine , cxcl9 , medicine , colorectal cancer , oncology , gene signature , cxcl10 , immune system , cxcl16 , cancer , immunology , cancer research , biology , gene expression , gene , biochemistry
Tertiary lymphoid structures (TLSs) provide an immunological antineoplastic effect. Recent evidences link a unique 12‐chemokine (CCL2, ‐3, ‐4, ‐5, ‐8, ‐18, ‐19, ‐21, CXCL9, ‐10, ‐11, ‐13) signature status from tumor tissue and the TLS expression. However, the potential significance of 12‐chemokine signature status for clinical use is unknown. We aimed to evaluate the association of 12‐chemokine signature status with patient outcomes in colorectal cancer (CRC). We used integrated data of resected 975 CRC cases within three independent cohorts from France, Japan and the United States (GSE39582, KUMAMOTO from Kumamoto university hospital and TCGA). The association of 12‐chemokine signature status with clinicopathological features, patient outcome, TLS expression status and key tumor molecular features was analyzed. Patients with low 12‐chemokine signature status had a significant shorter relapse‐free survival in discovery cohort (HR: 1.61, 95% CI: 1.11–2.39, p = 0.0123), which was confirmed in validation cohort (HR: 3.31, 95% CI: 1.33–10.08, p = 0.0087). High 12‐chemokine signature status had significant associations with right‐sided tumor, high tumor‐localized TLS expression, BRAF mutant, CIMP‐high status and MSI‐high status. Furthermore, RNA‐seq based analysis showed that high 12‐chemokine signature status was strongly associated with inflammation‐related, immune cells‐related and apoptosis pathways (using gene set enrichment analysis), and more tumor‐infiltrating immune cells, such as cytotoxic T lymphocytes and myeloid dendritic cells (using MCP‐counter analysis). We investigated a promising effect of 12‐chemokine signature status in CRC patients who underwent resection. Our data may be helpful in developing novel immunological treatment strategies for CRC.