Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype

Sang Cheul Oh, Bo Hwa Sohn, Jae Ho Cheong, Sang Bae Kim, Jae Eun Lee, Ki Cheong Park, Sang Ho Lee, Jong Lyul Park, Yun Yong Park, Hyun Sung Lee, Hee Jin Jang, Eun Sung Park, Sang Cheol Kim, Jeonghoon Heo, In Sun Chu, You Jin Jang, Young Jae Mok, Wonkyung Jung, Baek Hui Kim, Aeree KimJae Yong Cho, Jae Yun Lim, Yuki Hayashi, Shumei Song, Elena Elimova, Jeannelyn S. Estralla, Jeffrey H. Lee, Manoop S. Bhutani, Yiling Lu, Wenbin Liu, Jeeyun Lee, Won Ki Kang, Sung Kim, Sung Hoon Noh, Gordon Mills, Seon Young Kim, Jaffer A. Ajani, Ju Seog Lee

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Gastric cancer is a heterogeneous cancer, making treatment responses difficult to predict. Here we show that we identify two distinct molecular subtypes, mesenchymal phenotype (MP) and epithelial phenotype (EP), by analyzing genomic and proteomic data. Molecularly, MP subtype tumors show high genomic integrity characterized by low mutation rates and microsatellite stability, whereas EP subtype tumors show low genomic integrity. Clinically, the MP subtype is associated with markedly poor survival and resistance to standard chemotherapy, whereas the EP subtype is associated with better survival rates and sensitivity to chemotherapy. Integrative analysis shows that signaling pathways driving epithelial-to-mesenchymal transition and insulin-like growth factor 1 (IGF1)/IGF1 receptor (IGF1R) pathway are highly activated in MP subtype tumors. Importantly, MP subtype cancer cells are more sensitive to inhibition of IGF1/IGF1R pathway than EP subtype. Detailed characterization of these two subtypes could identify novel therapeutic targets and useful biomarkers for prognosis and therapy response.

Original languageEnglish (US)
Article number1777
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

Fingerprint

phenotype
Somatomedins
Stomach Neoplasms
Tumors
Chemotherapy
cancer
Phenotype
insulin
Biomarkers
Microsatellite Repeats
tumors
Cells
chemotherapy
Neoplasms
integrity
Somatomedin Receptors
microsatellites
Drug Therapy
Epithelial-Mesenchymal Transition
prognosis

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Oh, S. C., Sohn, B. H., Cheong, J. H., Kim, S. B., Lee, J. E., Park, K. C., ... Lee, J. S. (2018). Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype. Nature Communications, 9(1), [1777]. https://doi.org/10.1038/s41467-018-04179-8

Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype. / Oh, Sang Cheul; Sohn, Bo Hwa; Cheong, Jae Ho; Kim, Sang Bae; Lee, Jae Eun; Park, Ki Cheong; Lee, Sang Ho; Park, Jong Lyul; Park, Yun Yong; Lee, Hyun Sung; Jang, Hee Jin; Park, Eun Sung; Kim, Sang Cheol; Heo, Jeonghoon; Chu, In Sun; Jang, You Jin; Mok, Young Jae; Jung, Wonkyung; Kim, Baek Hui; Kim, Aeree; Cho, Jae Yong; Lim, Jae Yun; Hayashi, Yuki; Song, Shumei; Elimova, Elena; Estralla, Jeannelyn S.; Lee, Jeffrey H.; Bhutani, Manoop S.; Lu, Yiling; Liu, Wenbin; Lee, Jeeyun; Kang, Won Ki; Kim, Sung; Noh, Sung Hoon; Mills, Gordon; Kim, Seon Young; Ajani, Jaffer A.; Lee, Ju Seog.

In: Nature Communications, Vol. 9, No. 1, 1777, 01.12.2018.

Research output: Contribution to journalArticle

Oh, SC, Sohn, BH, Cheong, JH, Kim, SB, Lee, JE, Park, KC, Lee, SH, Park, JL, Park, YY, Lee, HS, Jang, HJ, Park, ES, Kim, SC, Heo, J, Chu, IS, Jang, YJ, Mok, YJ, Jung, W, Kim, BH, Kim, A, Cho, JY, Lim, JY, Hayashi, Y, Song, S, Elimova, E, Estralla, JS, Lee, JH, Bhutani, MS, Lu, Y, Liu, W, Lee, J, Kang, WK, Kim, S, Noh, SH, Mills, G, Kim, SY, Ajani, JA & Lee, JS 2018, 'Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype', Nature Communications, vol. 9, no. 1, 1777. https://doi.org/10.1038/s41467-018-04179-8
Oh, Sang Cheul ; Sohn, Bo Hwa ; Cheong, Jae Ho ; Kim, Sang Bae ; Lee, Jae Eun ; Park, Ki Cheong ; Lee, Sang Ho ; Park, Jong Lyul ; Park, Yun Yong ; Lee, Hyun Sung ; Jang, Hee Jin ; Park, Eun Sung ; Kim, Sang Cheol ; Heo, Jeonghoon ; Chu, In Sun ; Jang, You Jin ; Mok, Young Jae ; Jung, Wonkyung ; Kim, Baek Hui ; Kim, Aeree ; Cho, Jae Yong ; Lim, Jae Yun ; Hayashi, Yuki ; Song, Shumei ; Elimova, Elena ; Estralla, Jeannelyn S. ; Lee, Jeffrey H. ; Bhutani, Manoop S. ; Lu, Yiling ; Liu, Wenbin ; Lee, Jeeyun ; Kang, Won Ki ; Kim, Sung ; Noh, Sung Hoon ; Mills, Gordon ; Kim, Seon Young ; Ajani, Jaffer A. ; Lee, Ju Seog. / Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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AU - Cheong, Jae Ho

AU - Kim, Sang Bae

AU - Lee, Jae Eun

AU - Park, Ki Cheong

AU - Lee, Sang Ho

AU - Park, Jong Lyul

AU - Park, Yun Yong

AU - Lee, Hyun Sung

AU - Jang, Hee Jin

AU - Park, Eun Sung

AU - Kim, Sang Cheol

AU - Heo, Jeonghoon

AU - Chu, In Sun

AU - Jang, You Jin

AU - Mok, Young Jae

AU - Jung, Wonkyung

AU - Kim, Baek Hui

AU - Kim, Aeree

AU - Cho, Jae Yong

AU - Lim, Jae Yun

AU - Hayashi, Yuki

AU - Song, Shumei

AU - Elimova, Elena

AU - Estralla, Jeannelyn S.

AU - Lee, Jeffrey H.

AU - Bhutani, Manoop S.

AU - Lu, Yiling

AU - Liu, Wenbin

AU - Lee, Jeeyun

AU - Kang, Won Ki

AU - Kim, Sung

AU - Noh, Sung Hoon

AU - Mills, Gordon

AU - Kim, Seon Young

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AU - Lee, Ju Seog

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