Oncogenic Pathway Combinations Predict Clinical Prognosis in Gastric Cancer

被引：349

作者：

Ooi, Chia Huey ^{[1
]}

Ivanova, Tatiana

Wu, Jeanie

Lee, Minghui

Tan, Iain Beehuat ^{[2
]}

Tao, Jiong ^{[3
]}

Ward, Lindsay ^{[4
]}

Koo, Jun Hao

Gopalakrishnan, Veena

Zhu, Yansong

Cheng, Lai Ling ^{[5
]}

Lee, Julian

Rha, Sun Young ^{[6
]}

Chung, Hyun Cheol ^{[6
]}

Ganesan, Kumaresan

So, Jimmy ^{[7
]}

Soo, Khee Chee ^{[8
]}

Lim, Dennis ^{[9
]}

Chan, Weng Hoong ^{[9
]}

Wong, Wai Keong ^{[9
]}

Bowtell, David ^{[10
]}

Yeoh, Khay Guan ^{[11
]}

Grabsch, Heike ^{[4
]}

Boussioutas, Alex ^{[10
,12
]}

Tan, Patrick ^{[1
,13
,14
]}

机构：

[1] Duke NUS Grad Med Sch, Singapore, Singapore

[2] Natl Canc Ctr, Div Med Oncol, Singapore, Singapore

[3] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117595, Singapore

[4] St James Univ Hosp, Leeds Inst Mol Med, Sect Pathol & Tumour Biol, Leeds LS9 7TF, W Yorkshire, England

[5] Natl Univ Singapore, Singapore MIT Alliance, Singapore 117548, Singapore

[6] Yonsei Univ, Coll Med, Dept Internal Med, Yonsei Canc Ctr, Seoul, South Korea

[7] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Surg, Singapore 117595, Singapore

[8] Natl Canc Ctr, Div Surg Oncol, Singapore, Singapore

[9] Singapore Gen Hosp, Dept Gen Surg, Singapore 169608, Singapore

[10] Peter MacCallum Canc Ctr, Canc Genom & Biochem Lab, Melbourne, Vic, Australia

[11] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117595, Singapore

[12] Univ Melbourne, Western Hosp, Dept Med RMH WH, Footscray, Vic, Australia

[13] Natl Univ Singapore, Yong Loo Lin Sch Med, Canc Sci Inst Singapore, Singapore 117595, Singapore

[14] Genome Inst Singapore, Singapore, Singapore

来源：

PLOS GENETICS | 2009年 / 5卷 / 10期

关键词：

FACTOR-KAPPA-B; GENE-EXPRESSION; TRANSCRIPTION FACTOR; TARGET GENES; CELL-CYCLE; CARCINOMA; BETA; IDENTIFICATION; ACTIVATION; DISTINCT;

D O I：

10.1371/journal.pgen.1000676

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Many solid cancers are known to exhibit a high degree of heterogeneity in their deregulation of different oncogenic pathways. We sought to identify major oncogenic pathways in gastric cancer (GC) with significant relationships to patient survival. Using gene expression signatures, we devised an in silico strategy to map patterns of oncogenic pathway activation in 301 primary gastric cancers, the second highest cause of global cancer mortality. We identified three oncogenic pathways (proliferation/stem cell, NF-kappa B, and Wnt/beta-catenin) deregulated in the majority (>70%) of gastric cancers. We functionally validated these pathway predictions in a panel of gastric cancer cell lines. Patient stratification by oncogenic pathway combinations showed reproducible and significant survival differences in multiple cohorts, suggesting that pathway interactions may play an important role in influencing disease behavior. Individual GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Predicting pathway activity by expression signatures thus permits the study of multiple cancer-related pathways interacting simultaneously in primary cancers, at a scale not currently achievable by other platforms.

引用

页数：13

共 52 条

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