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 Kim; Jae 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 B. Mills; Seon Young Kim; Jaffer A. Ajani; Ju Seog Lee

doi:10.1038/s41467-018-04179-8

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 B. Mills, Seon Young Kim, Jaffer A. Ajani, Ju Seog Lee

Research output: Contribution to journal › Article › peer-review

214 Scopus citations

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 language	English (US)
Article number	1777
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-04179-8
State	Published - Dec 1 2018

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Oh, S. C., Sohn, B. H., Cheong, J. H., Kim, S. B., Lee, J. E., Park, K. C., Lee, S. H., Park, J. L., Park, Y. Y., Lee, H. S., Jang, H. J., Park, E. S., Kim, S. C., Heo, J., Chu, I. S., Jang, Y. J., Mok, Y. J., Jung, W., Kim, B. H., ... Lee, J. S. (2018). Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype. Nature communications, 9(1), Article 1777. https://doi.org/10.1038/s41467-018-04179-8

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, GB, 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

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title = "Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype",

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.",

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

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AU - Oh, Sang Cheul

AU - Sohn, Bo Hwa

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 B.

AU - Kim, Seon Young

AU - Ajani, Jaffer A.

AU - Lee, Ju Seog

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

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Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype

Abstract

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MD Anderson CCSG core facilities

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