Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype

被引：304

作者：

Oh, Sang Cheul ^{[1
,2
]}

Sohn, Bo Hwa ^{[1
,3
]}

Cheong, Jae-Ho ^{[4
]}

Kim, Sang-Bae ^{[1
,3
]}

Lee, Jae Eun ^{[4
]}

Park, Ki Cheong ^{[4
]}

Lee, Sang Ho ^{[5
]}

Park, Jong-Lyul ^{[6
]}

Park, Yun-Yong ^{[7
]}

Lee, Hyun-Sung ^{[1
,3
]}

Jang, Hee-Jin ^{[1
,3
]}

Park, Eun Sung ^{[8
]}

Kim, Sang-Cheol ^{[9
]}

Heo, Jeonghoon ^{[10
]}

Chu, In-Sun ^{[11
]}

Jang, You-Jin ^{[12
]}

Mok, Young-Jae ^{[12
]}

Jung, WonKyung ^{[12
]}

Kim, Baek-Hui ^{[13
]}

Kim, Aeree ^{[13
]}

Cho, Jae Yong ^{[14
]}

Lim, Jae Yun ^{[14
]}

Hayashi, Yuki ^{[15
]}

Song, Shumei ^{[15
]}

Elimova, Elena ^{[15
]}

Estralla, Jeannelyn S. ^{[15
]}

Lee, Jeffrey H. ^{[15
]}

Bhutani, Manoop S. ^{[15
,16
]}

Lu, Yiling ^{[1
,3
]}

Liu, Wenbin ^{[1
,3
]}

Lee, Jeeyun ^{[17
]}

Kang, Won Ki ^{[17
]}

Kim, Sung ^{[18
]}

Noh, Sung Hoon ^{[4
]}

Mills, Gordon B. ^{[1
,3
]}

Kim, Seon-Young ^{[6
]}

Ajani, Jaffer A. ^{[15
]}

Lee, Ju-Seog ^{[1
,3
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA

[2] Korea Univ, Guro Hosp, Div Hematooncol, Dept Internal Med, Seoul 08308, South Korea

[3] Univ Texas MD Anderson Canc Ctr, Inst Personalized Canc Therapy, Houston, TX 77030 USA

[4] Yonsei Univ, Coll Med, Dept Surg, Seoul 03722, South Korea

[5] Kosin Univ, Dept Surg, Coll Med, Busan 49267, South Korea

[6] Korea Res Inst Biosci & Biotechnol, Personalized Genom Med Res Ctr, Daejeon 34141, South Korea

[7] Univ Ulsan, ASAN Inst Life Sci, Dept Med, ASAN Med Ctr,Coll Med, Seoul 05505, South Korea

[8] Inha Univ, Med Res Inst, Coll Med, Incheon 22212, South Korea

[9] Natl Inst Hlth, Dept Biomed Informat, Ctr Genome Sci, Daejeon 34141, South Korea

[10] Kosin Univ, Dept Mol Biol & Immunol, Coll Med, Busan 49267, South Korea

[11] Korea Res Inst Biosci & Biotechnol, Korean Bioinformat Ctr, Daejeon 34141, South Korea

[12] Korea Univ, Guro Hosp, Dept Surg, Coll Med, Seoul 08308, South Korea

[13] Korea Univ, Guro Hosp, Dept Pathol, Coll Med, Seoul 08308, South Korea

[14] Yonsei Univ, Coll Med, Med Oncol, Seoul 03722, South Korea

[15] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA

[16] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA

[17] Samsung Med Ctr, Div Hematol Oncol, Dept Med, Seoul 06351, South Korea

[18] Samsung Med Ctr, Dept Surg, Seoul 06351, South Korea

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

新加坡国家研究基金会; 美国国家卫生研究院;

关键词：

GASTROINTESTINAL STROMAL TUMORS; COMPREHENSIVE MOLECULAR CHARACTERIZATION; FREQUENT EPIGENETIC INACTIVATION; GROWTH-FACTOR RECEPTOR; PROGNOSTIC-FACTORS; TRANSITION; EXPRESSION; CARCINOMA; SUBTYPES; INSULIN;

D O I：

10.1038/s41467-018-04179-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14

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