Elevated expression of Nodal and YAP1 is associated with poor prognosis of gastric adenocarcinoma.
OBJECTIVE
To investigate the correlation between Nodal and YAP1 expression and the clinicopathological characteristics of gastric adenocarcinoma (GAC).


METHODS
Quantitative real-time RT-PCR, Western blot, and immunohistochemistry were performed to measure Nodal and YAP1 mRNA and protein in 20 fresh frozen samples and 220 paraffin-embedded GAC tissues with their paired non-tumor mucosa (PNTM). The prognostic values of Nodal and YAP1 were evaluated in 161 GAC patients using univariate and multivariate analyses.


RESULTS
Both mRNA and protein expression of Nodal and YAP1 were significantly increased in GAC compared to PNTM (P < 0.05). Immunohistochemistry showed that Nodal was more highly expressed in 56.4 % GAC samples compared to PNTM; additionally, Nodal expression correlated with depth of tumor invasion, lymph node metastasis, and distant metastasis (all P < 0.05). There was no association between Nodal and YAP1 in GAC (P = 0.171). Kaplan-Meier analysis showed that the outcome of Nodal-high patients was significantly worse than those with low Nodal expression (χ (2) = 30.452, P < 0.001). Cox multivariate regression showed that high Nodal expression was an independent risk factor affecting the prognosis of GAC patients (P = 0.000, RR = 2.976). Furthermore, patients with tumors in which both Nodal and YAP1 were expressed at high levels had the worst prognosis.


CONCLUSIONS
Elevated Nodal expression is a marker of poor prognosis in gastric cancer. Patient outcome is further worsened if Nodal and YAP1 are both expressed in the same tumor. The datas we present here suggest that the inhibition of Nodal signaling may represent a new therapeutic strategy for the treatment of gastric adenocarcinoma.
Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute and General Surgery Institute, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China.
Ping
P
Li
Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute and General Surgery Institute, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China.
Dan
D
Sun
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China.
Xiaoting
X
Li
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China.
Yingjian
Y
He
Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute and General Surgery Institute, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China.
Wenhui
W
Li
Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute and General Surgery Institute, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China.
Jing
J
Zhao
Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute and General Surgery Institute, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China.
Ying
Y
Wang
Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute and General Surgery Institute, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China.
Huan
H
Wang
Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute and General Surgery Institute, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China. yxin@mail.cmu.edu.cn.
Yan
Y
Xin
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055457:Nodal Protein / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors; D015854:Up-Regulation; D000091102:YAP-Signaling Proteins
D048868:Adaptor Proteins, Signal Transducing; C526007:NODAL protein, human; D055457:Nodal Protein; D010750:Phosphoproteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human
Gastric adenocarcinoma; Nodal; Prognosis; YAP1