title: Plastin3 is a novel marker for circulating tumor cells undergoing the epithelial-mesenchymal transition and is associated with colorectal cancer prognosis.
abstract: 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.
authors: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
authors: Takehiko
authors: T
authors: Yokobori
authors: Hisae
authors: H
authors: Iinuma
authors: Teppei
authors: T
authors: Shimamura
authors: Seiya
authors: S
authors: Imoto
authors: Keishi
authors: K
authors: Sugimachi
authors: Hideshi
authors: H
authors: Ishii
authors: Masaaki
authors: M
authors: Iwatsuki
authors: Daisuke
authors: D
authors: Ota
authors: Masahisa
authors: M
authors: Ohkuma
authors: Takeshi
authors: T
authors: Iwaya
authors: Naohiro
authors: N
authors: Nishida
authors: Ryunosuke
authors: R
authors: Kogo
authors: Tomoya
authors: T
authors: Sudo
authors: Fumiaki
authors: F
authors: Tanaka
authors: Kohei
authors: K
authors: Shibata
authors: Hiroyuki
authors: H
authors: Toh
authors: Tetsuya
authors: T
authors: Sato
authors: Graham F
authors: GF
authors: Barnard
authors: Takeo
authors: T
authors: Fukagawa
authors: Seiichiro
authors: S
authors: Yamamoto
authors: Hayao
authors: H
authors: Nakanishi
authors: Shin
authors: S
authors: Sasaki
authors: Satoru
authors: S
authors: Miyano
authors: Toshiaki
authors: T
authors: Watanabe
authors: Hiroyuki
authors: H
authors: Kuwano
authors: Koshi
authors: K
authors: Mimori
authors: Klaus
authors: K
authors: Pantel
authors: Masaki
authors: M
authors: Mori
mesh_terms: D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D008207:Lymphatic Metastasis; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D012333:RNA, Messenger; C026742:plastin