A novel strategy to identify candidate diagnostic and prognostic biomarkers for gastric cancer

Cancer Cell International

Biran Pan¹  Kaiwen Wu²  Xue Yao²  Honglin Pang²  Qiao He³  Xiaobin Sun⁴  Jing Shan⁴  Liping Wu⁴  Lei Liu⁵  Yuanbiao Guo⁵ 

[1]Assisted Reproductive Center, The Maternal and Child Health Hospital of Qinzhou, 535000, Qinzhou, Sichuan, China

[2]College of Medicine, Southwest Jiaotong University, 610036, Chengdu, Sichuan, China

[3]Department of Clinical Laboratory, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, 610031, Chengdu, Sichuan, China

[4]Department of Gastroenterology, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, 610031, Chengdu, Sichuan, China

[5]Medical Research Center, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, 82 Qinglong Road, 610031, Chengdu, Sichuan, China

关键词: Gastric cancer;    Diagnosis;    Prognosis;    Serum biomarkers;    Exosomes;   

DOI  :  10.1186/s12935-021-02007-6

来源: Springer

【 摘 要 】

BackgroundGastric cancer (GC) is one of the most common cancer worldwide. It is essential to identify non-invasive diagnostic and prognostic biomarkers of GC. The aim of the present study was to screen candidate biomarkers associated with the pathogenesis and prognosis of GC by a novel strategy.MethodsThe expression level of gene higher in cancer than in adjacent non-cancer tissue was defined as “positive”, and the top 5% genes with “positive rate” were filtered out as candidate diagnostic biomarkers in three Gene Expression Omnibus (GEO) datasets. Further, a prognostic risk model was constructed by multivariate Cox regression analysis in GEO dataset and validated in The Cancer Genome Atlas (TCGA). The expression level of candidate biomarkers was determined in serum and serum-derived exosomes of GC patients. Moreover, the effect of biomarkers in exosomes on migration of GC cells was analyzed by transwell assay.ResultsTen candidate biomarkers (AGT, SERPINH1, WNT2, LIPG, PLAU, COL1A1, MMP7, MXRA5, CXCL1 and COL11A1) were identified with efficient diagnostic value in GC. A prognostic gene signature consisted of AGT, SERPINH1 and MMP7 was constructed and showed a good performance in predicting overall survivals in TCGA. Consistently, serum levels of the three biomarkers also showed high sensitivity and specificity in distinguishing GC patients from controls. In addition, the expression level of the three biomarkers were associated with malignant degree and decreased after surgery in GC patients. Moreover, the expression level of AGT and MMP7 in exosomes correlated positively with serum level. The exosomes derived from serum of GC patients can promote migration of SGC‐7901 cells. After neutralized the expression level of three proteins in exosomes with antibodies, the migration of GC cells was obviously suppressed.ConclusionsOur findings provided a novel strategy to identify diagnostic biomarkers based on public datasets, and suggested that the three-gene signature was a candidate diagnostic and prognostic biomarker for patients with GC.

【 授权许可】

CC BY