Dataset Information

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

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.

SUBMITTER: Mitchell A

PROVIDER: S-EPMC8299666 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Mitchell Andrew A Hasanali Sarrah L SL Morera Daley S DS Baskar Rohitha R Wang Xin X Khan Rahil R Talukder Asif A Li Charles S CS Manoharan Meenakkshy M Jordan Andre R AR Wang Jiaojiao J Bollag Roni J RJ Singh Nagendra N Albo Daniel D Ghosh Santu S Lokeshwar Vinata B VB

Cancer biomarkers : section A of Disease markers 20190101 3

<h4>Background</h4>Differential expression of chemokines/chemokine receptors in colorectal cancer (CRC) may enable molecular characterization of patients' tumors for predicting clinical outcome.<h4>Objective</h4>To evaluate the prognostic ability of these molecules in a CRC cohort and the CRC TCGA-dataset.<h4>Methods</h4>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; c ...[more]

PMID: 31524146

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Project description:The clinical significance and comprehensive characteristics of chemokines and chemokine receptors in female patients with advanced colorectal adenocarcinoma have not ever been reported. Our study explored the expression profiles of chemokines and chemokine receptors and constructed a chemokine- and chemokine receptor-based signature in female patients with advanced colorectal adenocarcinoma. Four independent cohorts containing 1335 patients were enrolled in our study. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses were performed to construct the signature. CIBERSORT was used to evaluate the landscape of immune cell infiltration. Thirty-two pairs of tissue specimens of female advanced colorectal cancer (CRC) patients and two CRC cell lines were used to validate the signature in vitro. Quantitative real-time PCR and western blotting were performed to validate the mRNA and protein expression levels of signature genes. EdU and colony formation assays were performed to examine proliferative ability. Transwell and wound healing assays were used to evaluate cell invasion and migration capacity. During the signature construction and validation process, we found that the signature was more applicable to female patients with advanced colorectal adenocarcinoma. Hence, the subsequent study mainly focused on the particular subgroup. Enrichment analyses revealed that the signature was closely related to immunity. The landscape of immune cell infiltration presented that the signature was significantly associated with T cells CD8 and neutrophils. Gene set enrichment analysis (GSEA) confirmed that the high-risk group was chiefly enriched in the tumor-promoting related pathways and biological processes, whereas the low-risk group was mainly enriched in anti-tumor immune response pathways and biological processes. The signature was closely correlated with CTLA4, PDL1, PDL2, TMB, MSI, and TIDE, indicating that our signature could serve as a robust biomarker for immunotherapy and chemotherapy response. ROC curves verified that our signature had more robust prognostic power than all immune checkpoints and immunotherapy-related biomarkers. Finally, we used 32 pairs of tissue specimens and 2 CRC cell lines to validate our signature in vitro. We first provided a robust prognostic chemokine- and chemokine receptor-based signature, which could serve as a novel biomarker for immunotherapy and chemotherapy response to guide individualized treatment for female patients with advanced colorectal adenocarcinoma.

Dataset Information

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

Background

Objective

Methods

Results

Conclusions

Publications

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

Similar Datasets

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