机构：[1]Medical Research Center, The Third People’s Hospital of Chengdu, TheAffiliated Hospital of Southwest Jiaotong University, 82 Qinglong Road,Chengdu 610031, Sichuan, China[2]College of Medicine, Southwest JiaotongUniversity, Chengdu 610036, Sichuan, China[3]Department of Clinical Laboratory,Sichuan Cancer Center, School of Medicine, University of ElectronicScience and Technology of China, Chengdu 610031, Sichuan, China四川省肿瘤医院[4]AssistedReproductive Center, The Maternal and Child Health Hospital of Qinzhou,Qinzhou 535000, Sichuan, China[5]Department of Gastroenterology, The ThirdPeople’s Hospital of Chengdu, The Affiliated Hospital of Southwest JiaotongUniversity, Chengdu 610031, Sichuan, China
Background Gastric 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. Methods The 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. Results Ten 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. Conclusions Our 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.
基金：
Foundation of Science and Technology
Department of Sichuan province (2020YFS0492, 2020YJ0485) and Medical
Research Project of Chengdu Municipal Health Commission (2018080).
第一作者机构：[1]Medical Research Center, The Third People’s Hospital of Chengdu, TheAffiliated Hospital of Southwest Jiaotong University, 82 Qinglong Road,Chengdu 610031, Sichuan, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Liu Lei,Pang Honglin,He Qiao,et al.A novel strategy to identify candidate diagnostic and prognostic biomarkers for gastric cancer[J].CANCER CELL INTERNATIONAL.2021,21(1):doi:10.1186/s12935-021-02007-6.
APA：
Liu, Lei,Pang, Honglin,He, Qiao,Pan, Biran,Sun, Xiaobin...&Guo, Yuanbiao.(2021).A novel strategy to identify candidate diagnostic and prognostic biomarkers for gastric cancer.CANCER CELL INTERNATIONAL,21,(1)
MLA：
Liu, Lei,et al."A novel strategy to identify candidate diagnostic and prognostic biomarkers for gastric cancer".CANCER CELL INTERNATIONAL 21..1(2021)
