Oncoscience

ZC3H12A Expression in Different Stages of Colorectal Cancer

Tao Chen1, Di Du2, Jian Chen3, Pinghong Zhou1, John N. Weinstein2, Liqing Yao1, Yuexin Liu2

1Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital of Fudan University, Shanghai, China

2Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

3Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Correspondence to:

Yuexin Liu, email:yliu8@mdanderson.org

Keywords: ZC3H12A; Colorectal Cancer; biomarker; early detection

Received: December 19, 2018 Accepted: February 1, 2019 Published: April 2, 2018

Abstract

Identification of CRC patients with early-stage disease provides the opportunity for curative local resection. However, robust markers for stage I tumor prediction are yet to be developed. In the TCGA cohort, stage I CRC patients had significantly higher ZC3H12A mRNA expression as compared with the other three stages combined and with the other individual stages in a pairwise manner (P<0.001 for all comparisons). The significant association of ZC3H12A gene expression with stages was further validated in the GEO cohort and in the additional third cohort. In support of these findings, we further found that patients with lower ZC3H12A expression had more aggressive tumor features and shorter disease-free survival. Biologically, ZC3H12A expression was significantly correlated with expression of three chemokine ligands (CXCL1, CXCL2 and CXCL3), suggesting that immune response dysregulation likely contributes to CRC development. We analyzed RNA-sequencing data of 221 CRC samples using the TCGA dataset to identify novel biomarkers for stage I CRC. We next validated the TCGA finding in an independent GEO cohort of 290 CRC patients and in a third cohort of 110 CRC tumors and matched normal samples. We further performed correlative analysis of ZC3H12A gene expression with clinicopathologic features and disease-free survival. Expression correlation of ZC3H12A with the chemokine ligands was evaluated via Student’s t-test. Our results demonstrate ZC3H12A’s potential role in identification of CRC patients with early-stage disease.


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