br levels of CDCP were significantly increased
levels of CDCP1 were significantly increased in GC serum as well as tu-mour tissues. (2) DDAH1 is an endogenous nitric oxide synthase inhib-itor, for which Ye et al. reported that downregulation of DDAH1 was more frequently detected in GC tumour tissues and strongly correlated with aggressive phenotypes and poor prognosis . However, we ob-served increased DDAH1 levels in GC serum compared to controls, while no difference between GC tumour and adjacent normal tissue in our cohort. (3) PPIA, has been reported to be overexpressed in several types of human cancers including gastric cancer [51,55]. (4) HMOX1 is considered to be the main protein for cytoprotection against various cell stresses, and increased 4μ8C of this protein was observed in several types of cancers [56,57]. However, there are no differences in the levels of PPIA and HOMX1 between GC and controls in serum or in tissue in the present study.
(6) ADAMTS15. (1) A recent bioinformatic analysis based on genome-
wide association studies (GWAS) data identified IL7 pathway as one of the three pathways associated with GC risk . (2) ZBTA17, also known as MIZ1, is a transcription factor that forms a complex with Myc and mediates Myc-dependent tumorigenesis . (3) FLI11 is also a transcription factor, and its high level expression as well as trans-locations were observed in hematopoietic and solid tumours .
(4) KAZALD1 is a member of the insulin growth factor-binding protein (IGFBP) superfamily, and hypomethylation of the gene was found in cancer. “The Human Protein Atlas (HPA)” database (https://www. proteinatlas.org) shows a moderate staining (6/10) of KAZALD1 protein in stomach cancer tissues. In the present cohort, the levels of IL7, ZBTB17, FLI1, and KAZALD1 were all significantly increased in serum from GC patients as compared with controls, indicating that they may play roles in GC tumorigenesis and progress. (5) APBB1IP, also known as RIAM (Rap1-GTP-interacting adaptor molecule), appears to function
in the signal transduction from Ras activation to actin cytoskeletal re-modeling and mediates Rap1-induced adhesion. (6) ADAMTS15 is one of the extracellular metalloproteinases, which functions as a putative tumour suppressor, and has been linked to a number of different can-cers such as prostatic, breast and colorectal cancers . The HPA data-base displays a weak staining for APBB1IP and moderate for ADAMTS15 in 10 GC tissue sections. In our study, ADAMTS15 was also significantly downregulated in GC tissues compared to surrounding normal tissues.
Many of the 19 identified proteins are inflammation related, such as IL7, MMP1, MMP10, CCL20, CDCP1, SCF, and TGFA. As one of the conse-quences of long-term gastric inflammation is malignances, these markers may play important roles in GC development.
GCNT1 is a glycosyltransferase that adds beta1,6 GlcNAc arm to core 1 O-glycans and forms core 2 O-glycans. Core 2 O-glycans are known to be a particularly good scaffold for sialyl Lewis antigens, which can be recognized by selectin family members and thereby mediate leukocyte rolling and cancer cell metastasis . GCNT1 was significantly in-creased in sera of GC patients compared to controls in univariate analy-sis, and was the most significantly increased serum protein in GC patients at TNM I-II stage as well as in high MSI patients. However, there was no change of GCNT1 between tumour and adjacent normal tissues for patients at early stage or with MSI. This indicates that the in-crease of GCNT1 in serum may be due to inflammation or unleashed im-mune response. As most blood proteins are glycoproteins and alterations of O-linked glycosylation is related to a majority of cancers, the function role and underline mechanisms of GCNT1 in gastric cancer needs further investigation.