Alu-based cell-free DNA: a novel biomarker for screening of gastric cancer.

Chen Qian,Hui Cong,Jing Qi,Juan Yu,Zhiwei Wang,Shaoqing Ju,Rongrong Jing,Li Li,Xianjuan Shen,Jianmei Zhao,Lurong Zhang,Yingjuan Shi

doi:10.18632/oncotarget.11079

Abstract

Gastric cancer (GC) is the fourth most common cancer and the second major cause of cancer-related deaths worldwide. In our previous study, a novel and sensitive method for quantifying cell-free DNA (CFD) in human blood was established and tested for its ability to predict patients with tumor. We want to investigate CFD expression in the sera of GC patients in an attempt to explore the clinical significance of CFD in improving the early screening of GC and monitoring GC progression by the branched DNA (bDNA)-based Alu assay. The concentration of CFD was quantitated by bDNA-based Alu assay. CEA, CA19-9, C72-4 and CA50 concentrations were determined by ABBOTT ARCHITECT I2000 SR. We found the CFD concentrations have significant differences between GC patients, benign gastric disease (BGD) patients and healthy controls (P < 0.05). CFD were weakly correlated with CEA (r = −0.197, P < 0.05) or CA50 (r = 0.206, P < 0.05), and no correlation with CA19-9 (r = −0.061, P > 0.05) or CA72-4 (r = 0.011, P > 0.05). In addition, CFD concentrations were significantly higher in stage I GC patients than BGD patients and healthy controls (P < 0.05), but there was no significant difference in CEA, CA19-9 and CA50 among the three traditional tumor markers (P > 0.05). Our analysis showed that CFD was more sensitive than CEA, CA19-9, CA72-4 or CA50 in early screening of GC. Compared with CEA, CA19-9, CA72-4 and CA50, CFD may prove to be a better biomarker for the screening of GC, thus providing a sensitive biomarker for screening and monitoring progression of GC.

Highlights

Advances in molecular diagnosis and therapeutic approaches for gastric cancer (GC) have decreased the mortality rates of Gastric cancer (GC) patients in recent years, but it is still remains the fourth most common cancer and the second major cause of cancer-related deaths worldwide [1,2,3,4]
cell-free DNA (CFD) concentrations were significantly higher in stage I GC patients than benign gastric disease (BGD) patients and healthy controls (P < 0.05), but there was no significant difference in CEA, CA19-9 and CA50 among the three traditional tumor markers (P > 0.05)
Our analysis showed that CFD was more sensitive than CEA, CA19-9, CA72-4 or CA50 in early screening of GC

Summary

Introduction

Advances in molecular diagnosis and therapeutic approaches for gastric cancer (GC) have decreased the mortality rates of GC patients in recent years, but it is still remains the fourth most common cancer and the second major cause of cancer-related deaths worldwide [1,2,3,4]. Tumor-associated antigens on the surface of GC cells, including CEA, CA72-4 and CA50, can be used as indicators for early screening of GC, they are handicapped by high false positive and negative rates, low specificity www.impactjournals.com/oncotarget and sensitivity. A combined detection system is needed [5], and researchers have made every effort in an attempt to find a minimally traumatic, sensitive, reliable and GC-specific tumor marker to improve early screening. Compared with real-time PCR, the new method improved the detection sensitivity by increasing the labeled probe copy number or signal intensity of the marker without amplifying the target sequences, overcoming the false positive rate of PCR detection [7,8,9]. More CFD of Alu repeat sequences could be detected in serum, which theoretically has more universal significance

Methods

Results

Conclusion