A chemokine/chemokine receptor signature potentially predicts clinical outcome in colorectal cancer patients

Andrew Mitchell, Sarrah L. Hasanali, Daley S. Morera, Rohitha Baskar, Xin Wang, Rahil Khan, Asif Talukder, Charles S. Li, Meenakkshy Manoharan, Andre R. Jordan, Jiaojiao Wang, Roni J. Bollag, Nagendra Singh, Daniel Albo, Santu Ghosh, Vinata B. Lokeshwar

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

BACKGROUND: Differential expression of chemokines/chemokine receptors in colorectal cancer (CRC) may enable molecular characterization of patients' tumors for predicting clinical outcome. OBJECTIVE: To evaluate the prognostic ability of these molecules in a CRC cohort and the CRC TCGA-dataset. METHODS: Chemokine (CXCL-12α, CXCL-12β, IL-17A, CXCL-8, GM-CSF) and chemokine receptor (CXCR-4, CXCR-7) transcripts were analyzed by RT-qPCR in 76 CRC specimens (normal: 27, tumor: 49; clinical cohort). RNA-Seq data was analyzed from the TCGA-dataset (n= 375). Transcript levels were correlated with outcome; analyses: univariate, multivariable, Kaplan-Meier. RESULTS: In the clinical cohort, chemokine/chemokine receptor levels were elevated 3-10-fold in CRC specimens (P⩽ 0.004) and were higher in patients who developed metastasis (P= 0.03 - < 0.0001). CXCR-4, CXCR-7, CXCL-12α, CXCL-8, IL-17 and GM-CSF levels predicted metastasis (P⩽ 0.0421) and/or overall survival (OS; P⩽ 0.0373). The CXCR-4+CXCR-7+CXCL-12 marker (CXCR-4/7+CXCL-12 (α/b) signature) stratified patients into risk for metastasis (P= 0.0014; OR, 2.72) and OS (P= 0.0442; OR, 2.7); sensitivity: 86.67%, specificity: 97.06%. In the TCGA-dataset, the CXCR-4/7+CXCL-12 signature predicted metastasis (P= 0.011; OR, 2.72) and OS (P= 0.0006; OR: 4.04). In both datasets, the signature was an independent predictor of clinical outcome. CONCLUSIONS: Results of 451 specimens from both cohorts reveal that the CXCR-4/7+CXCL-12 signature potentially predicts outcome in CRC patients and may allow earlier intervention.

Original languageEnglish (US)
Pages (from-to)291-301
Number of pages11
JournalCancer biomarkers : section A of Disease markers
Volume26
Issue number3
DOIs
StatePublished - Jan 1 2019

Keywords

  • colorectal cancer
  • CXCL-12
  • CXCL-8
  • CXCR-4
  • CXCR-7

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

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