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Fucosyltransferase-4 and Oligosaccharide Lewis Y Antigen as potentially Correlative Biomarkers of Helicobacter pylori CagA Associated Gastric Cancer

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Pathology & Oncology Research

Abstract

H. pylori cytotoxin associated antigen A (CagA) plays a significant role in the progression of gastric cancer but their effect on fucosylation to develop gastric cancer is unknown. Fucosyltransferase IV (FUT4) is the key enzyme for synthesis of LewisY (LeY) carried by glycoproteins and glycolipids on the cell membrane. Herein, we compare the expression of CagA, p-EGFR, FUT4 and LeY in gastritis (n = 128, 176), gastric ulcer (n = 174, 213), and gastric cancer (n = 323, 261) tissue and serum samples, respectively by IHC and ELISA. Moreover, we investigated the potential correlation of CagA with FUT4 and LeY overexpression through EGFR activation. IHC and ELISA results showed higher positive cases of H. pylori CagA (83, 86 %), p-EGFR (81, 72 %), FUT4 (91, 97 %) and LeY (93, 92 %) in gastric cancer, compared to gastritis and gastric ulcer, H. pylori CagA (58, 67 & 59, 73 %), p-EGFR (52, 63 & 35, 47 %), FUT4 (68, 78 & 67, 82 %) and LeY (62,76 & 65, 85 %), respectively. We found a significant high expression (H-Value) of CagA (1.79, 1.66), p-EGFR (1.53, 1.58), FUT4 (2.14, 1.66) and LeY (1.69, 1.61) in gastric cancer tissues and serum, respectively as compared to chronic gastritis and gastric ulcers, CagA (0.64,1.14), p-EGFR (0.856, 0.678), FUT4 (0.949,1.197) and LeY (0.68,1.008) (P < 0.0001), respectively. Furthermore, H. pylori CagA showed significant correlation with p-EGFR (R–0.62, −0.74), FUT4 (R–0.81, −0.76) and LeY (R–0.82, −0.70) in gastric tissues and serum (P < 0.0001). H. pylori CagA plays key role in the development of gastric cancer with overexpression of FUT4/LeY, serve as potentially correlative biomarkers of H. pylori CagA associated gastric cancer.

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Abbreviations

H. pylori :

Helicobacter pylori

CagA:

Cytotoxin associated antigen A

CAG:

Chronic atrophic gastritis

EGFR:

Epidermal growth factor receptor

FUTs:

Fucosyltransferases

GED:

Gastric epithelial dysplasia

GC:

Gastric cancer

GIs:

Chronic gastritis

GU:

Gastric ulcer

IHC:

Immunohistochemistry

IM:

Intestinal metaplasia

LeY:

Lewis Y

p-EGFR:

Phosphorylated epidermal growth factor receptor

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Acknowledgments

The project was supported by the China 973 grant no. 2012CB822100, National Natural Science Foundation of China Research grants no. 30672753 and 31270866.

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Correspondence to Qiu Yan.

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Aziz, F., Gao, W. & Yan, Q. Fucosyltransferase-4 and Oligosaccharide Lewis Y Antigen as potentially Correlative Biomarkers of Helicobacter pylori CagA Associated Gastric Cancer. Pathol. Oncol. Res. 23, 173–179 (2017). https://doi.org/10.1007/s12253-016-0122-1

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  • DOI: https://doi.org/10.1007/s12253-016-0122-1

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