Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis

被引：742

作者：

Ueda, Tetsuya ^{[1
,2
,4
]}

Volinia, Stefano ^{[1
,2
,6
]}

Okumura, Hiroshi ^{[1
,2
,3
]}

Shimizu, Masayoshi ^{[7
]}

Taccioli, Cristian ^{[1
,2
]}

Rossi, Simona ^{[6
,7
]}

Alder, Hansjuerg ^{[1
,2
]}

Liu, Chang-gong ^{[1
,2
,7
]}

Oue, Naohide ^{[8
]}

Yasui, Wataru ^{[8
]}

Yoshida, Kazuhiro ^{[9
,10
]}

Sasaki, Hiroki ^{[11
]}

Nomura, Sachiyo ^{[4
]}

Seto, Yasuyuki ^{[4
]}

Kaminishi, Michio ^{[4
,5
]}

Calin, George A. ^{[7
]}

Croce, Carlo M. ^{[1
,2
]}

机构：

[1] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA

[2] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA

[3] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Surg Oncol & Digest Surg, Kagoshima 890, Japan

[4] Univ Tokyo, Grad Sch Med, Dept Gastrointestinal Surg, Tokyo, Japan

[5] Showa Gen Hosp, Dept Surg, Tokyo, Japan

[6] Univ Ferrara, Dept Morphol & Embryol, I-44100 Ferrara, Italy

[7] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Expt Therapeut, Houston, TX 77030 USA

[8] Hiroshima Univ, Grad Sch Biomed Sci, Dept Mol Pathol, Hiroshima, Japan

[9] Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Surg Oncol, Hiroshima, Japan

[10] Gifu Univ, Sch Med, Dept Surg Oncol, Gifu 500, Japan

[11] Natl Canc Ctr, Res Inst, Div Genet, Tokyo 104, Japan

来源：

LANCET ONCOLOGY | 2010年 / 11卷 / 02期

关键词：

DIFFUSE-TYPE; CELL; PROFILES; IDENTIFICATION; DEREGULATION; SIGNATURES; TARGET; GROWTH;

D O I：

10.1016/S1470-2045(09)70343-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background Analyses of microRNA expression profiles have shown that many microRNAs are expressed aberrantly and correlate with tumorigenesis, progression, and prognosis of various haematological and solid tumours. We aimed to assess the relation between microRNA expression and progression and prognosis of gastric cancer. Methods 353 gastric samples from two independent subsets of patients from Japan were analysed by microRNA microarray. MicroRNA expression patterns were compared between non-tumour mucosa and cancer samples, graded by diffuse and intestinal histological types and by progression-related factors (eg, depth of invasion, metastasis, and stage). Disease outcome was calculated by multivariable regression analysis to establish whether microRNAs are independent prognostic factors. Findings In 160 paired samples of non-tumour mucosa and cancer, 22 microRNAs were upregulated and 13 were downregulated in gastric cancer; 292 (83%) samples were distinguished correctly by this signature. The two histological subtypes of gastric cancer showed different microRNA signatures: eight microRNAs were upregulated in diffuse-type and four in intestinal-type cancer. In the progression-related signature, miR-125b, miR-199', and miR-100 were the most important microRNAs involved. Low expression of let-7g (hazard ratio 2.6 [95% CI 1.3-4.91) and miR-433 (2.1 [1.1-3.9]) and high expression of miR-214 (2.4 [1.2-4.51) were associated with unfavourable outcome in overall survival independent of clinical covariates, including depth of invasion, lymph-node metastasis, and stage. Interpretation MicroRNAs are expressed differentially in gastric cancers, and histological subtypes are characterised by specific microRNA signatures. Unique microRNAs are associated with progression and prognosis of gastric cancer.

引用

页码：136 / 146

页数：11

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