title: Expression of tumoral FOXP3 in gastric adenocarcinoma is associated with favorable clinicopathological variables and related with Hippo pathway.
abstract: FOXP3 is a transcription factor and well-known hallmark of immune suppressive T regulatory cells (Tregs). Recent studies indicate that, in addition to its association with Treg function in the immune system, FOXP3 plays an important role in tumor development. And important tumor suppressor relay between the FOXP3 and Hippo pathways was found in human cancer. Thus, we investigated tumoral FOXP3, infiltrated Tregs count, Lats2, and YAP expression in gastric adenocarcinoma, and the relationships between expression of these three proteins and p53, Ki67, and other clinicopathological variables. We used 118 gastric adenocarcinoma tissues via immunohistochemical analysis, using a tissue microarray, in relation to survival and other clinicopathological factors. We report the several novel observations about the relationship between tumoral FOXP3 and Hippo pathway components in gastric adenocarcinoma. Positive tumoral FOXP3 expression was significantly related with smaller tumor size, tubular tumor type, lower histological grade, lower T stage, lower recurrence rate, less lymphatic invasion, and less neural invasion. Furthermore, patients with positive tumoral FOXP3 experienced significantly better disease-free and overall survival compared to patients with negative tumoral FOXP3. These findings show that tumoral FOXP3 expression is associated with favorable clinicopathological variables in gastric adenocarcinoma. And we report the novel observation of a relationship between tumoral FOXP3 and Hippo pathway components in gastric adenocarcinoma. Tumoral FOXP3 expression, infiltrated Tregs count, and Lats2 expression were all positively correlated with YAP expression. These findings suggest that the Hippo pathway in gastric adenocarcinoma might be influenced by both tumoral FOXP3 and infiltrated Tregs. In conclusion, the loss of FOXP3 expression in cancer cells is thought to contribute to tumorigenesis and progression of gastric adenocarcinoma. The expression of FOXP3 in gastric adenocarcinoma is related with Lats2 and YAP expression of the Hippo pathway.
authors.affiliation: Department of Internal Medicine, Graduate School of Medicine, Kyung Hee University Seoul, South Korea.
authors.forename: Jung-Ho
authors.initials: JH
authors.lastname: Suh
authors.affiliation: Department of Pathology, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University Seoul, South Korea.
authors.forename: Kyu Yeoun
authors.initials: KY
authors.lastname: Won
authors.affiliation: Department of Pathology, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University Seoul, South Korea.
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Kim
authors.affiliation: Department of Pathology, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University Seoul, South Korea.
authors.forename: Go Eun
authors.initials: GE
authors.lastname: Bae
authors.affiliation: Department of Pathology, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University Seoul, South Korea.
authors.forename: Sung-Jig
authors.initials: SJ
authors.lastname: Lim
authors.affiliation: Department of Pathology, Kyung Hee University Hospital, School of Medicine, Kyung Hee University Seoul, South Korea.
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Sung
authors.affiliation: Department of Pathology, Kyung Hee University Hospital, School of Medicine, Kyung Hee University Seoul, South Korea.
authors.forename: Yong-Koo
authors.initials: YK
authors.lastname: Park
authors.affiliation: Department of Pathology, Kyung Hee University Hospital, School of Medicine, Kyung Hee University Seoul, South Korea.
authors.forename: Youn Wha
authors.initials: YW
authors.lastname: Kim
authors.affiliation: Department of Pathology, Kyung Hee University Hospital, School of Medicine, Kyung Hee University Seoul, South Korea.
authors.forename: Juhie
authors.initials: J
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D018797:Cell Cycle Proteins; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000096:biosynthesis*; D000090683:Hippo Signaling Pathway; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C456659:YY1AP1 protein, human; C406449:LATS2 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: FOXP3; Gastric adenocarcinoma; Lats2; YAP
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