Development and validation of a novel glycolysis-related risk signature for predicting survival in pancreatic adenocarcinoma

Ang Li; Sinan Hou; Jian Chen; Yanfang Jiang

doi:10.1016/j.cca.2021.03.020

Development and validation of a novel glycolysis-related risk signature for predicting survival in pancreatic adenocarcinoma

Clin Chim Acta. 2021 Jul:518:156-161. doi: 10.1016/j.cca.2021.03.020. Epub 2021 Mar 26.

Authors

Ang Li¹, Sinan Hou², Jian Chen³, Yanfang Jiang⁴

Affiliations

¹ Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun 130021, China.
² Department of Clinical Laboratory Medicine, Lianyungang Traditional Chinese Medicine Hospital, Lianyungang, Jiangsu 222002, China.
³ Department of Gastroenterology, Zhongda Hospital affiliated to Southeast University, Nanjing 210009, China.
⁴ Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun 130021, China. Electronic address: yanfangjiang@jlu.edu.cn.

PMID: 33775699
DOI: 10.1016/j.cca.2021.03.020

Abstract

Background: Pancreatic adenocarcinoma (PAAD) is one of the leading causes of cancer-related deaths worldwide. Through data mining, an increasing number of biomarkers have been identified to predict the survival of patients with PAAD. However, the ability of single gene biomarkers to predict patient survival is still insufficient. This study aimed to develop a novel risk signature for predicting the survival of patients with PAAD.

Methods: mRNA expression profiling was performed for a large PAAD cohort (n = 177) identified using The Cancer Genome Atlas database (TCGA). Gene set enrichment analysis (GSEA) was performed to detect whether the gene sets showed significant differences between PAAD and adjacent normal tissues. Univariate Cox regression was used to analyze and identify genes related to overall survival (OS). Multivariate Cox regression was subsequently used to confirm the prognostic genes and obtain the coefficients. By analyzing the expression level of selected genes weighted by their coefficients through linearly combining, we constructed a risk score formula for prognostic prediction. The three-mRNA signature for survival prediction was validated using the Kaplan-Meier method.

Results: We demonstrated that a set of three genes (KIF20A, CHST2, and MET) were significantly associated with OS. Based on this three-gene signature, 177 PAAD patients were classified into high-risk and low-risk groups using the median risk score as the cut-off value. We also validated the reliability of this three-gene signature in the GSE28735 dataset from the Gene Expression Omnibus (GEO) database. Additionally, multivariate Cox regression analysis revealed that the three-gene signature had an independent prognostic value.

Conclusion: To the best of our knowledge, this is the first study to develop a glycolysis-related risk signature for predicting the survival of patients with pancreatic adenocarcinoma. Our findings provide insight into the identification of PAAD patients with poor prognosis. We also identified novel therapeutic targets for this disease.

Keywords: Glycolysis; Pancreatic adenocarcinoma; Risk signature; Survival.

MeSH terms

Adenocarcinoma* / diagnosis
Adenocarcinoma* / genetics
Gene Expression Regulation, Neoplastic
Glycolysis / genetics
Humans
Pancreatic Neoplasms* / diagnosis
Pancreatic Neoplasms* / genetics
Reproducibility of Results