Analysis of immune‑related signatures of colorectal cancer identifying two different immune phenotypes: Evidence for immune checkpoint inhibitor therapy

Chen,Gang; Wang,Lin; Diao,Tongwei; Chen,Ying; Cao,Chengbo; Zhang,Xindong

doi:10.3892/ol.2020.11605

Analysis of immune‑related signatures of colorectal cancer identifying two different immune phenotypes: Evidence for immune checkpoint inhibitor therapy

Authors:
- Gang Chen
- Lin Wang
- Tongwei Diao
- Ying Chen
- Chengbo Cao
- Xindong Zhang
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Affiliations: Department of Anal and Intestinal Surgery, Tengzhou Central People's Hospital, Tengzhou, Shandong 277500, P.R. China, Department of Surgery Operating Room, Tengzhou Central People's Hospital, Tengzhou, Shandong 277500, P.R. China, Department of Pathology, Tengzhou Central People's Hospital, Tengzhou, Shandong 277500, P.R. China
Published online on: May 13, 2020 https://doi.org/10.3892/ol.2020.11605
Pages: 517-524
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of numerous types of cancer, including colorectal cancer (CRC). Patients with CRC and deficient mismatch repair or high microsatellite instability could benefit from ICI treatment, although the response rate of most patients is low. Therefore, the immune subtyping of patients with CRC is required in order to determine the subtypes suitable for ICI treatment. The present study used a cohort of patients with CRC from The Cancer Genome Atlas (TCGA) to perform molecular subtyping, with results validated in three CRC cohorts from the Gene Expression Omnibus. Non‑negative matrix factorization was used to achieve consensus molecular subtyping. The tumor immune dysfunction and exclusion algorithm was used to predict potential ICI therapy responses and gene set enrichment analysis was performed to define different pathways associated with the immune response. Two distinct subtypes of CRC were finally identified in TCGA cohorts, which were characterized as significantly different prognostic subtypes (low‑risk and high‑risk subtypes). Higher expression of programmed death‑ligand 1, higher proportion of tumor‑infiltrating lymphocytes and tumor mutation burden were significantly enriched in the low‑risk subtype. Further pathway analysis revealed that the low‑risk subtype was associated with immune response activation and signaling pathways involved in ‘antigen processing and presentation’. Three independent CRC cohorts were used to validate the above findings. In summary, two clinical CRC subtypes were identified, which are characterized by significantly different survival outcomes and immune infiltration patterns. The findings of the present study suggest that ICI treatment may be more effective in the low‑risk CRC subtype.

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