254P - Elucidation of the mechanism of high-lymph node metastasis density in gastric cancer-H19-PEG10 axis

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Gastric Cancer
Translational Research
Presenter Satoru Ishii
Citation Annals of Oncology (2016) 27 (suppl_9): ix68-ix85. 10.1093/annonc/mdw582
Authors S. Ishii, K. Yamashita, T. Tanaka, N. Nishizawa, K. Yokoi, H. Katoh, M. Watanabe
  • Surgery, Kitasato University School of Medicine, 252-0375 - Sagamihara/JP

Abstract

Background

Lymph node ratio (LNR) is the ratio of metastatic lymph nodes to the lymph node dissection, in recent years it has become known as a strong prognostic factor and considered for inclusion of new staging system in gastric cancer. However, there has been no comprehensive study to identify molecules that showed the expression and the mechanisms associated with LNR in advanced gastric cancer. Therefore, we aim to reveal the molecular mechanism and select molecules that indicate the expression associated with a high LNR in advanced gastric cancer.

Methods

In pathological Stage III (JCGC13) advanced gastric cancer tumor specimens, the candidate genes associated with high LNR were selected using a microarray for patients with high LNR (n = 4) and those with low (n = 4), and non-cancerous gastric mucosa as a control (n = 2). The identified candidate genes have been verified as an association with high LNR in 39 Stage III advanced gastric cancer patients.

Results

Rigorous analysis of the microarray result identified 5 candidate genes as H19, PEG10, IGF2BP3, CD177, and PGA3. Correlation between the five candidate genes and LNR has been verified by semi-quantitative RT-PCR in clinical specimens 39 cases. H19 and PEG10 showed a high expression frequency and significant difference (82.4%vs36.4%, 70.6%vs40.9%, p = 0.004, p = 0.034, respectively) in high LNR group compared with low. Intriguingly, there was significant association in expression between H19 gene and PEG10 gene (p = 0.0002).

Conclusions

In recent years, H19 has been reported to be involved in proliferation, invasion, and metastasis through epithelial-mesenchymal transition (EMT). On the other hand, PEG10 also has been elucidated for relationship with proliferation and invasion, metastasis. Primary cancer with high LNR showed high expression of both genes, so therapeutic effects of both gene knockdown are promising to identify molecular target signals in gastric cancer with high LNR, which is a clinical concern.

Clinical trial indentification

no

Legal entity responsible for the study

Kitasato University School of Medicine, Surgery

Funding

Merck Serono Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.