title: Overexpression of ADP-ribosylation factor 1 in human gastric carcinoma and its clinicopathological significance.
abstract: Gastric cancer is the sixth leading cause of cancer-related death in Taiwan, and the identification of related factors is essential to increase patient survival. ADP-ribosylation factor 1 (ARF1) was initially identified using 2-D electrophoresis combined with MALDI-time-of-flight mass spectrometry. ADP-ribosylation factor 1 belongs to the Ras superfamily or GTP-binding protein family and has been shown to enhance cell proliferation. In the current study, we evaluated the potential of ARF1 as a biomarker for gastric cancer detection. ADP-ribosylation factor 1 mRNA was upregulated in tumor tissues (compared with adjacent non-tumor tissues, n = 55) in approximately 67.2% of gastric cancer patients. Expression of ARF1 protein was additionally observed using Western blot and immunohistochemistry (IHC) analyses. The clinicopathological correlations of ARF1 were further evaluated. Elevated ARF1 expression was strongly correlated with lymph node metastasis (P = 0.008), serosal invasion (P = 0.046), lymphatic invasion (P = 0.035), and pathological staging (P = 0.010). Moreover, the 5-year survival rate for the lower ARF1 expression group (n = 50; IHC score < 90) was higher than that of the higher expression group (n = 60; IHC score ≥ 90) (P = 0.0228, log-rank test). To establish the specific function of ARF1 in human gastric cancer, isogenic ARF1-overexpressing cell lines were prepared. Our results showed that ARF1-overexpressing clones display enhanced cell proliferation, migration, and invasion. Furthermore, ARF1-overexpression might contribute to poor prognosis of patients. These findings collectively support the utility of ARF1 as a novel prognostic marker for gastric cancer and its role in cell invasion.
authors.affiliation: Department of Biochemistry, Chang-Gung University, Taoyuan, Taiwan.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Tsai
authors.forename: Paul Y
authors.initials: PY
authors.lastname: Lin
authors.forename: Wan-Li
authors.initials: WL
authors.lastname: Cheng
authors.forename: Chung-Ying
authors.initials: CY
authors.lastname: Tsai
authors.forename: Hsiang-Cheng
authors.initials: HC
authors.lastname: Chi
authors.forename: Cheng-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Yi-Hsin
authors.initials: YH
authors.lastname: Tseng
authors.forename: Yi-Fen
authors.initials: YF
authors.lastname: Cheng
authors.forename: Chi-De
authors.initials: CD
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Liao
authors.forename: Sheng-Ming
authors.initials: SM
authors.lastname: Wu
authors.forename: Yang-Hsiang
authors.initials: YH
authors.lastname: Lin
authors.forename: I-Hsiao
authors.initials: IH
authors.lastname: Chung
authors.forename: Chia-Siu
authors.initials: CS
authors.lastname: Wang
authors.forename: Kwang-Huei
authors.initials: KH
authors.lastname: Lin
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000096:biosynthesis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D020823:ADP-Ribosylation Factor 1