Clinical and molecular assessment of an onco-immune signature with prognostic significance in patients with colorectal cancer

Pankaj Ahluwalia, Ashis K. Mondal, Meenakshi Ahluwalia, Nikhil S. Sahajpal, Kimya Jones, Yasmeen Jilani, Gagandeep K. Gahlay, Amanda Barrett, Vamsi Kota, Amyn Mohammed Rojiani, Ravindra Kolhe

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Understanding the complex tumor microenvironment is key to the development of personalized therapies for the treatment of cancer including colorectal cancer (CRC). In the past decade, significant advances in the field of immunotherapy have changed the paradigm of cancer treatment. Despite significant improvements, tumor heterogeneity and lack of appropriate classification tools for CRC have prevented accurate risk stratification and identification of a wider patient population that may potentially benefit from targeted therapies. To identify novel signatures for accurate prognostication of CRC, we quantified gene expression of 12 immune-related genes using a medium-throughput NanoString quantification platform in 93 CRC patients. Multivariate prognostic analysis identified a combined four-gene prognostic signature (TGFB1, PTK2, RORC, and SOCS1) (HR: 1.76, 95% CI: 1.05–2.95, *p < 0.02). The survival trend was captured in an independent gene expression data set: GSE17536 (177 patients; HR: 3.31, 95% CI: 1.99–5.55, *p < 0.01) and GSE14333 (226 patients; HR: 2.47, 95% CI: 1.35–4.53, *p < 0.01). Further, gene set enrichment analysis of the TCGA data set associated higher prognostic scores with epithelial–mesenchymal transition (EMT) and inflammatory pathways. Comparatively, a lower prognostic score was correlated with oxidative phosphorylation and MYC and E2F targets. Analysis of immune parameters identified infiltration of T-reg cells, CD8+ T cells, M2 macrophages, and B cells in high-risk patient groups along with upregulation of immune exhaustion genes. This molecular study has identified a novel prognostic gene signature with clinical utility in CRC. Therefore, along with prognostic features, characterization of immune cell infiltrates and immunosuppression provides actionable information that should be considered while employing personalized medicine.

Original languageEnglish (US)
Pages (from-to)1573-1586
Number of pages14
JournalCancer Medicine
Volume11
Issue number6
DOIs
StatePublished - Mar 2022

Keywords

  • colon
  • colorectal cancer
  • gene signature
  • immune
  • personalized medicine
  • preventive
  • prognostic genes

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Fingerprint

Dive into the research topics of 'Clinical and molecular assessment of an onco-immune signature with prognostic significance in patients with colorectal cancer'. Together they form a unique fingerprint.

Cite this