Abstract
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.
Highlights
Gastric cancer (GC) is one of the most common cancer worldwide
The expression level of gene higher in cancer than in adjacent non-cancer tissue were define as positive, and we believe that the positive rate of candidate biomarkers in cancer patients is as important as its difference in concentration between cancer patients and healthy people
The 239 genes were annotated by Cellular Components analysis of Gene Ontology (GO), and 16 proteins were located in extracellular region: AGT, SERPINH1, ATR, WNT2, LIPG, PLAU, COL1A1, SERPINB5, MMP7, WNT5A, MXRA5, CTSC, HPSE, CXCL16, CXCL1 and COL11A1 (Fig. 2)
Summary
Gastric cancer (GC) is one of the most common cancer worldwide. It is essential to identify non-invasive diagnostic and prognostic biomarkers of GC. Gastric cancer (GC) is one of the most common cancer worldwide and is responsible for over 1,000,000 new cases in 2018 and an estimated 783,000 deaths, making it the fifth most frequently diagnosed cancer and the third leading cause of cancer death. Liu et al Cancer Cell Int (2021) 21:335 survival of GC is low because more than 80% of patients are diagnosed at an advanced stage and lose the opportunity for the most effective surgical treatment [2, 3]. Several blood markers have been used for diagnosis, determination of the clinical stage, evaluation of treatment responses and screening for recurrence after successful therapy [4]. As current non-invasive tests are insufficient for GC screening or diagnosis, the discovery of alternative biomarkers is necessary, especially blood biomarkers
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