title: Autophagy is related to the hedgehog signaling pathway in human gastric adenocarcinoma: prognostic significance of Beclin-1 and Gli2 expression in human gastric adenocarcinoma.
abstract: Beclin-1 induces autophagy, which is known to be involved in many physiopathological processes such as cell development, aging, stress response, immune response and cancer. Several studies showed that Beclin-1 expression is associated with several prognostic factors of gastric carcinomas. Recently, the connection between autophagy and the hedgehog (HH) signaling pathway has been studied. Here, we investigated the relationship between the autophagy and hedgehog (HH) signaling pathways in gastric adenocarcinoma. We evaluated Beclin-1 and Gli2 expression in 108 gastric adenocarcinoma tissues via immunohistochemical analysis, using a tissue microarray, in relation to survival and other prognostic factors. Our results show that increased Beclin-1 expression is correlated with favorable clinicopathological variables including histologic grade, tumor size, primary tumor (T) stage, lymph node metastasis, lymphatic invasion, neural invasion, and tumor recurrence. Furthermore, increased Gli-2 expression was correlated with several favorable clinicopathological variables including primary tumor (T) stage, lymphatic invasion, and tumor recurrence. Increased Beclin-1 expression was significantly correlated with increased Gli2. Univariate analyses for disease-free survival and overall survival revealed that the higher Beclin-1 and Gli2 expression group had a more favorable prognosis compared with the lower Beclin-1 and Gli2 expression group. Our results suggest that progressively increased Beclin-1 and Gli2 expression contributes to the inhibition of tumor growth and metastasis in gastric adenocarcinoma and Beclin-1 acts as a tumor suppressor by regulating the HH signaling pathway through Gli2 expression in gastric adenocarcinoma.
authors.affiliation: Department of Pathology, Kyung Hee University Hospital at Gangdong, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Kyu Yeoun
authors.initials: KY
authors.lastname: Won
authors.affiliation: Department of Pathology, Kyung Hee University Hospital at Gangdong, Kyung Hee University, Seoul, Republic of Korea. Electronic address: pathogen@medimail.co.kr.
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Kim
authors.affiliation: Department of Pathology, Kyung Hee University Hospital at Gangdong, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Sung-Jig
authors.initials: SJ
authors.lastname: Lim
authors.affiliation: Department of Pathology, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Sung
authors.affiliation: Department of Pathology, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Youn Wha
authors.initials: YW
authors.lastname: Kim
authors.affiliation: Department of Pathology, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Yong-Koo
authors.initials: YK
authors.lastname: Park
authors.affiliation: Department of Pathology, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Juhie
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Pathology, Graduate School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Hee Seung
authors.initials: HS
authors.lastname: Choi
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001343:Autophagy; D000071186:Beclin-1 / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000075746:Zinc Finger Protein Gli2
chemical_list: C491997:BECN1 protein, human; D000071186:Beclin-1; C082593:GLI2 protein, human; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D000075746:Zinc Finger Protein Gli2
keywords: Beclin-1; Gastric adenocarcinoma; Gli2