Plastin3 Is a Novel Marker for Circulating Tumor Cells Undergoing the Epithelial-Mesenchymal Transition and Is Associated with Colorectal Cancer Prognosis

被引：200

作者：

Yokobori, Takehiko ^{[1
,2
]}

Iinuma, Hisae ^{[3
]}

Shimamura, Teppei ^{[4
]}

Imoto, Seiya ^{[4
]}

Sugimachi, Keishi ^{[1
]}

Ishii, Hideshi ^{[1
]}

Iwatsuki, Masaaki ^{[1
]}

Ota, Daisuke ^{[1
]}

Ohkuma, Masahisa ^{[1
]}

Iwaya, Takeshi ^{[1
]}

Nishida, Naohiro ^{[1
]}

Kogo, Ryunosuke ^{[1
]}

Sudo, Tomoya ^{[1
]}

Tanaka, Fumiaki ^{[1
]}

Shibata, Kohei ^{[1
]}

Toh, Hiroyuki ^{[7
]}

Sato, Tetsuya ^{[7
]}

Barnard, Graham F. ^{[10
]}

Fukagawa, Takeo ^{[5
]}

Yamamoto, Seiichiro ^{[6
]}

Nakanishi, Hayao ^{[8
]}

Sasaki, Shin ^{[7
]}

Miyano, Satoru ^{[4
]}

Watanabe, Toshiaki ^{[3
]}

Kuwano, Hiroyuki ^{[2
]}

Mimori, Koshi ^{[1
]}

Pantel, Klaus ^{[11
]}

Mori, Masaki ^{[9
]}

机构：

[1] Kyushu Univ, Beppu Hosp, Dept Surg, Beppu, Oita, Japan

[2] Gunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi, Gunma 371, Japan

[3] Teikyo Univ, Sch Med, Dept Surg, Itabashi Ku, Tokyo 173, Japan

[4] Univ Tokyo, Inst Med Sci, Human Genome Ctr, Minato Ku, Tokyo, Japan

[5] Natl Canc Ctr, Dept Surg, Chuo Ku, Tokyo, Japan

[6] Omori Red Cross Hosp, Dept Surg, Ota Ku, Tokyo, Japan

[7] Kyushu Univ, Med Inst Bioregulat, Div Bioinformat, Fukuoka 812, Japan

[8] Aichi Canc Ctr, Res Inst, Div Oncol Pathol, Nagoya, Aichi 464, Japan

[9] Osaka Univ, Dept Surg Gastroenterol, Grad Sch Med, Suita, Osaka 5650871, Japan

[10] Univ Massachusetts, Med Ctr, Dept Med, Div Gastroenterol, Worcester, MA USA

[11] Univ Med Ctr Hamburg Eppendorf, Inst Tumor Biol, Hamburg, Germany

来源：

CANCER RESEARCH | 2013年 / 73卷 / 07期

基金：

日本科学技术振兴机构; 日本学术振兴会;

关键词：

PERIPHERAL-BLOOD; BREAST-CANCER; EXPRESSION; GENE; CARCINOMA; CHALLENGES; RESISTANCE;

D O I：

10.1158/0008-5472.CAN-12-0326

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Circulating tumor cells (CTC) in blood have attracted attention both as potential seeds for metastasis and as biomarkers. However, most CTC detection systems might miss epithelial-mesenchymal transition (EMT)-induced metastatic cells because detection is based on epithelial markers. First, to discover novel markers capable of detecting CTCs in which EMT has not been repressed, microarray analysis of 132 colorectal cancers (CRC) from Japanese patients was conducted, and 2,969 genes were detected that were overexpressed relative to normal colon mucosa. From the detected genes, we selected those that were overexpressed CRC with distant metastasis. Then, we analyzed the CRC metastasis-specific genes (n = 22) to determine whether they were expressed in normal circulation. As a result, PLS3 was discovered as a CTC marker that was expressed in metastatic CRC cells but not in normal circulation. Using fluorescent immunocytochemistry, we validated that PLS3 was expressed in EMT-induced CTC in peripheral blood from patients with CRC with distant metastasis. PLS3-expressing cells were detected in the peripheral blood of approximately one-third of an independent set of 711 Japanese patients with CRC. Multivariate analysis showed that PLS3-positive CTC was independently associated with prognosis in the training set (n = 381) and the validation set [n = 330; HR = 2.17; 95% confidence interval (CI) = 1.38-3.40 and HR = 3.92; 95% CI = 2.27-6.85]. The association between PLS3-positive CTC and prognosis was particularly strong in patients with Dukes B (HR = 4.07; 95% CI = 1.50-11.57) and Dukes C (HR = 2.57; 95% CI = 1.42-4.63). PLS3 is a novel marker for metastatic CRC cells, and it possesses significant prognostic value. Cancer Res; 73(7); 2059-69. (C)2012 AACR.

引用

页码：2059 / 2069

页数：11

共 43 条

[41] Lamin A/C Is a Risk Biomarker in Colorectal Cancer [J].

Willis, Naomi D. ;

Cox, Thomas R. ;

Rahman-Casans, Syed F. ;

Smits, Kim ;

Przyborski, Stefan A. ;

van den Brandt, Piet ;

van Engeland, Manon ;

Weijenberg, Matty ;

Wilson, Robert G. ;

de Bruine, Adriaan ;

Hutchison, Christopher J. .

PLOS ONE, 2008, 3 (08)

[42] Circulating tumour cells during laparoscopic and open surgery for primary colonic cancer in portal and peripheral blood [J].

Wind, J. ;

Tuynman, J. B. ;

Tibbe, A. G. J. ;

Swennenhuis, J. F. ;

Richel, D. J. ;

Henegouwen, M. I. van Berge ;

Bemelman, W. A. .

EJSO, 2009, 35 (09) :942-950

[43] p53-Altered FBXW7 Expression Determines Poor Prognosis in Gastric Cancer Cases [J].

Yokobori, Takehiko ;

Mimori, Koshi ;

Iwatsuki, Masaaki ;

Ishii, Hideshi ;

Onoyama, Ichiro ;

Fukagawa, Takeo ;

Kuwano, Hiroyuki ;

Nakayama, Keiichi I. ;

Mori, Masaki .

CANCER RESEARCH, 2009, 69 (09) :3788-3794

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