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World J Gastroenterol. Sep 28, 2006; 12(36): 5884-5889
Published online Sep 28, 2006. doi: 10.3748/wjg.v12.i36.5884
ECA39 is a novel distant metastasis-related biomarker in colorectal cancer
Tomoko Hashimoto-Tamaoki, Tomonori Morinaga, Yoshiro Nakano, Haruki Okamura, Takehira Yamamura, Tsutomu Oshima, Makoto Gega, Toshihiko Yagyu, Masafumi Noda, Yoshinori Fujiwara, Chun-Shen Shen, Hidenori Yanagi, Reigetsu Yoshikawa
Reigetsu Yoshikawa, Hidenori Yanagi, Yoshinori Fujiwara, Masafumi Noda, Toshihiko Yagyu, Makoto Gega, Tsutomu Oshima, Yoshinori Fujiwara, Takehira Yamamura, Second Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
Reigetsu Yoshikawa, Haruki Okamura, Tomoko Hashimoto-Tamaoki, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
Chun-Shen Shen, Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
Yoshiro Nakano, Tomonori Morinaga, Tomoko Hashimoto-Tamaoki, Department of Genetics, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
Author contributions: All authors contributed equally to the work.
Supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan, grant No. 16591374, and by Grant-in-Aid for Researchers, Hyogo College of Medicine
Correspondence to: Reigetsu Yoshikawa, MD, PhD, Second Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. yosikr2s@hyo-med.ac.jp
Telephone: +81-798-456372 Fax: +81-798-456373
Received: June 7, 2006
Revised: August 10, 2006
Accepted: August 17, 2006
Published online: September 28, 2006
Abstract

AIM: To investigate the possible role of polysaccharide-K (PSK) -related markers in predicting distant metastasis and in the clinical outcome of colorectal cancer (CRC).

METHODS: Firstly, we used protein microarrays to analyze the in vitro expression profiles of potential PSK-related markers in the human colorectal adenocarcinoma cell line SW480, which carries a mutant p53 gene. Then, we investigated the clinical implications of these markers in the prognosis of CRC patients.

RESULTS: ECA39, a direct target of c-Myc, was identified as a candidate protein affected by the anti-metastatic effects of PSK. Immunohistochemistry revealed that ECA39 was expressed at significantly higher levels in tumor tissues with distant metastases compared to those without (P < 0.00001). Positive ECA39 expression was shown to be highly reliable for the prediction of distant metastases (sensitivity: 86.7%, specificity: 90%, positive predictive value: 86.7%, negative predictive value: 90%). A significantly higher cumulative 5-yr disease free survival rate was observed in the ECA39-negative patient group (77.3%) compared with the ECA39-positive patient group (25.8%) (P < 0.05).

CONCLUSION: Our results suggest that ECA39 is a dominant predictive factor for distant metastasis in patients with advanced CRC and that its suppression by PSK might represent a useful application of immunotherapy as part of a program of integrated medicine.

Keywords: ECA39; Distant metastasis; Colorectal cancer; Polysaccharide-K; Integrated medicine
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