title: Implication of Leptin-Signaling Proteins and Epstein-Barr Virus in Gastric Carcinomas.
abstract: We investigated the clinicopathological implications of leptin-signaling proteins and Epstein-Barr virus (EBV)-infection status in gastric carcinomas. Immunohistochemistry for leptin signalling-related proteins (leptin, leptin-receptor, pSTAT3, ERK, pAkt, mTOR and HIF-1 alpha), and in situ hybridization for EBV-encoded small RNAs was performed in 343 cases of gastric carcinomas. The siRNA against leptin-receptor was transfected into three stomach cancer cell lines, and western blot for caspase 3 was performed. The TNM stage was a prognostic factor in all 343 patients, and was negatively correlated with expression of leptin, pSTAT3, ERK, pAkt, mTOR and HIF-1 alpha (P < 0.05). Leptin-receptor expression was correlated with poor survival in 207 patients of the advanced gastric cancer (AGC) subgroup, 139 of the Lauren diffuse group, and in 160 patients with lymph node metastasis (P < 0.05, respectively). Additionally, in stomach cancer cells, cleaved caspase 3 level increased by leptin-receptor inhibition, that is, apoptosis increased. Interestingly, EBV-positive AGC (n = 29) tended to show better survival of patients than EBV-negative AGC (n = 178) (P = 0.06). pAkt expression was related with a good survival of 32 patients (9%) in the EBV-positive subgroup, but was not an independent prognostic factor. Among, leptin signaling-related proteins, expressions of leptin-receptor and mTOR were different between EBV-positive subgroup and EBV-negative subgroup (P < 0.05, respectively). In conclusion, leptin-signaling proteins and EBV status show different significance on patient survival, according to subsets of gastric carcinomas. The leptin-receptor may predict poor patient prognosis in the AGC, Lauren diffuse and lymph node metastasis subgroups, while EBV-positive status can show a good prognosis in the AGC. Each leptin signaling-related protein may be differently involved in carcinogenesis of EBV-negative and EBV-positive subsets.
authors.affiliation: Department of Pathology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Euno
authors.initials: E
authors.lastname: Choi
authors.affiliation: Department of Surgery, Seoul National University Boramae Hospital, Seoul, Korea.
authors.forename: Sun-ju
authors.initials: SJ
authors.lastname: Byeon
authors.affiliation: Department of Pathology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Soo Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyeong Ju
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: Department of Surgery, Seoul National University Boramae Hospital, Seoul, Korea.
authors.forename: HyeSeong
authors.initials: H
authors.lastname: Ahn
authors.affiliation: Department of Pathology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dong Ha
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Mee Soo
authors.initials: MS
authors.lastname: Chang
mesh_terms: D045744:Cell Line, Tumor; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D017403:In Situ Hybridization; D020738:Leptin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology*
chemical_list: D020738:Leptin