ECA39 is a novel distant metastasis-related biomarker in colorectal cancer.
OBJECTIVE
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).


CONCLUSIONS
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.
Yoshikawa
Reigetsu
R
Second Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. yosikr2s@hyo-med.ac.jp
Yanagi
Hidenori
H
Shen
Chun-Shen
CS
Fujiwara
Yoshinori
Y
Noda
Masafumi
M
Yagyu
Toshihiko
T
Gega
Makoto
M
Oshima
Tsutomu
T
Yamamura
Takehira
T
Okamura
Haruki
H
Nakano
Yoshiro
Y
Morinaga
Tomonori
T
Hashimoto-Tamaoki
Tomoko
T
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D011509:Proteoglycans / Q000494:pharmacology; D012680:Sensitivity and Specificity; D000637:Transaminases / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D014408:Biomarkers, Tumor; D011509:Proteoglycans; D016159:Tumor Suppressor Protein p53; C010770:polysaccharide-K; C490590:BCAT1 protein, human; D000637:Transaminases