Suh Jung-Ho, Won Kyu Yeoun, Kim Gou Young, Bae Go Eun, Lim Sung-Jig, Sung Ji-Youn, Park Yong-Koo, Kim Youn Wha, Lee Juhie
Department of Internal Medicine, Graduate School of Medicine, Kyung Hee University Seoul, South Korea.
Department of Pathology, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University Seoul, South Korea.
Int J Clin Exp Pathol. 2015 Nov 1;8(11):14608-18. eCollection 2015.
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.
FOXP3是一种转录因子，也是免疫抑制性调节性T细胞（Tregs）的著名标志。最近的研究表明，除了在免疫系统中与Treg功能相关外，FOXP3在肿瘤发展中也起着重要作用。在人类癌症中发现了FOXP3与Hippo通路之间重要的肿瘤抑制传递。因此，我们研究了胃腺癌中肿瘤性FOXP3、浸润性Tregs计数、Lats2和YAP的表达，以及这三种蛋白质的表达与p53、Ki67和其他临床病理变量之间的关系。我们通过组织微阵列免疫组化分析，使用118例胃腺癌组织，研究其与生存及其他临床病理因素的关系。我们报告了关于胃腺癌中肿瘤性FOXP3与Hippo通路成分之间关系的几个新发现。肿瘤性FOXP3阳性表达与较小的肿瘤大小、管状肿瘤类型、较低的组织学分级、较低的T分期、较低的复发率、较少的淋巴浸润和较少的神经浸润显著相关。此外，与肿瘤性FOXP3阴性的患者相比，肿瘤性FOXP3阳性的患者无病生存期和总生存期明显更好。这些发现表明，肿瘤性FOXP3表达与胃腺癌良好的临床病理变量相关。并且我们报告了胃腺癌中肿瘤性FOXP3与Hippo通路成分之间关系的新发现。肿瘤性FOXP3表达、浸润性Tregs计数和Lats2表达均与YAP表达呈正相关。这些发现表明，胃腺癌中的Hippo通路可能受到肿瘤性FOXP3和浸润性Tregs的共同影响。总之，癌细胞中FOXP3表达的缺失被认为有助于胃腺癌的发生和进展。胃腺癌中FOXP3的表达与Hippo通路的Lats2和YAP表达相关。
