BACKGROUND: The liver is the most common site for haematogenous metastasis of gastric cancer, and liver metastasis is fatal. METHODS: We conducted a transcriptomic analysis between metastatic foci in the liver, primary tumour and adjacent tissues from gastric cancer patients with metastasis limited to the liver. We determined mRNA expression levels in tumour tissues of 300 patients with gastric cancer via quantitative RT-PCR. The oncogenic phenotypes of GNG4 were determined with knockdown, knockout and forced expression experiments. We established and compared subcutaneous and liver metastatic mouse xenograft models of gastric cancer to reveal the roles of GNG4 in tumorigenesis in the liver. RESULTS: GNG4 was upregulated substantially in primary gastric cancer tissues as well as liver metastatic lesions. High levels of GNG4 in primary cancer tissues were associated with short overall survival and the likelihood of liver recurrence. Functional assays revealed that GNG4 promoted cancer cell proliferation, the cell cycle and adhesiveness. Tumour formation by GNG4-knockout cells was moderately reduced in the subcutaneous mouse model and strikingly attenuated in the liver metastasis mouse model. CONCLUSIONS: GNG4 expression may provide better disease monitoring for liver metastasis, and GNG4 may be a novel candidate therapeutic target for liver metastasis.
BACKGROUND: The liver is the most common site for haematogenous metastasis of gastric cancer, and liver metastasis is fatal. METHODS: We conducted a transcriptomic analysis between metastatic foci in the liver, primary tumour and adjacent tissues from gastric cancer patients with metastasis limited to the liver. We determined mRNA expression levels in tumour tissues of 300 patients with gastric cancer via quantitative RT-PCR. The oncogenic phenotypes of GNG4 were determined with knockdown, knockout and forced expression experiments. We established and compared subcutaneous and liver metastatic mouse xenograft models of gastric cancer to reveal the roles of GNG4 in tumorigenesis in the liver. RESULTS: GNG4 was upregulated substantially in primary gastric cancer tissues as well as liver metastatic lesions. High levels of GNG4 in primary cancer tissues were associated with short overall survival and the likelihood of liver recurrence. Functional assays revealed that GNG4 promoted cancer cell proliferation, the cell cycle and adhesiveness. Tumour formation by GNG4-knockout cells was moderately reduced in the subcutaneous mouse model and strikingly attenuated in the liver metastasis mouse model. CONCLUSIONS: GNG4 expression may provide better disease monitoring for liver metastasis, and GNG4 may be a novel candidate therapeutic target for liver metastasis.
Authors: Kohei Shitara; Mustafa Özgüroğlu; Yung-Jue Bang; Maria Di Bartolomeo; Mario Mandalà; Min-Hee Ryu; Lorenzo Fornaro; Tomasz Olesiński; Christian Caglevic; Hyun C Chung; Kei Muro; Eray Goekkurt; Wasat Mansoor; Raymond S McDermott; Einat Shacham-Shmueli; Xinqun Chen; Carlos Mayo; S Peter Kang; Atsushi Ohtsu; Charles S Fuchs Journal: Lancet Date: 2018-06-04 Impact factor: 79.321
Authors: Claudia Allemani; Tomohiro Matsuda; Veronica Di Carlo; Rhea Harewood; Melissa Matz; Maja Nikšić; Audrey Bonaventure; Mikhail Valkov; Christopher J Johnson; Jacques Estève; Olufemi J Ogunbiyi; Gulnar Azevedo E Silva; Wan-Qing Chen; Sultan Eser; Gerda Engholm; Charles A Stiller; Alain Monnereau; Ryan R Woods; Otto Visser; Gek Hsiang Lim; Joanne Aitken; Hannah K Weir; Michel P Coleman Journal: Lancet Date: 2018-01-31 Impact factor: 79.321
Authors: Sheraz R Markar; Sameh Mikhail; George Malietzis; Thanos Athanasiou; Christophe Mariette; Mitsuru Sasako; George B Hanna Journal: Ann Surg Date: 2016-06 Impact factor: 12.969
Authors: Hitomi Sakamoto; Marc A Attiyeh; Jeffrey M Gerold; Alvin P Makohon-Moore; Akimasa Hayashi; Jungeui Hong; Rajya Kappagantula; Lance Zhang; Jerry P Melchor; Johannes G Reiter; Alexander Heyde; Craig M Bielski; Alexander V Penson; Mithat Gönen; Debyani Chakravarty; Eileen M O'Reilly; Laura D Wood; Ralph H Hruban; Martin A Nowak; Nicholas D Socci; Barry S Taylor; Christine A Iacobuzio-Donahue Journal: Cancer Discov Date: 2020-03-19 Impact factor: 38.272