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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
Reigetsu Yoshikawa, Hidenori Yanagi, Chun-Shen Shen, Yoshinori Fujiwara, Masafumi Noda, Toshihiko Yagyu, Makoto Gega, Tsutomu Oshima, Takehira Yamamura, Haruki Okamura, Yoshiro Nakano, Tomonori Morinaga, Tomoko Hashimoto-Tamaoki
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