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Oncol Lett. 2018 Apr;15(4):4926-4936. doi: 10.3892/ol.2018.7911. Epub 2018 Jan 31.

Expression of Hippo pathway genes and their clinical significance in colon adenocarcinoma.

Author information

1
Department of Surgery, School of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.
2
Clinical Research Department, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea.
3
Department of Anatomy, Seoul National University, College of Medicine, Seoul 03080, Republic of Korea.

Abstract

Yes-associated protein 1 (YAP1) is a transcriptional regulator of the Hippo pathway, which regulates the development and progression of a number of types of cancer, including that of the colon. In the present study, the expression levels of Hippo pathway genes and their clinical significance were investigated in 458 patients with colon adenocarcinoma (COAD), the most frequently diagnosed neoplastic disease globally, using data obtained from The Cancer Genome Atlas database. Notably, mRNA expression of YAP1 was higher in COAD than in other types of gastrointestinal tract cancer. Expression of YAP1 mRNA was higher in COAD than in normal colon samples and was significantly higher in Tumor-Node-Metastasis (TNM) stages III-IV than in stages I-II. YAP1 protein levels, a protein primarily localized in the nucleus, was greater in TNM stages III-IV than in stages I-II. The level of pYAP1, which is inactive and localized in the cytoplasm, was significantly higher in TNM stages III-IV than in stages I-II. However, the YAP1/pYAP1 ratio, which is representative of activity, was higher in TNM stages III-IV than in stages I-II. High mRNA expression of YAP1, TAZ and TEAD4 was associated with a poor prognosis in patients with COAD. Bioinformatics analysis revealed that YAP1 was associated with DNA duplication, cell proliferation and development. Wnt signaling and transforming growth factor-β signaling were significantly higher in the high-YAP1 group, according to data from Gene Set Enrichment Analysis. Taken together, the results indicate that the subcellular distribution of YAP1 and high mRNA expression of YAP1, TAZ and TEAD4 may be associated with poorer overall survival rates in patients with COAD.

KEYWORDS:

Hippo signaling pathway; The Cancer Genome Atlas; colon adenocarcinoma; overall survival; yes-associated protein 1

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