Multidisciplinary Treatment against Colorectal Cancer Utilizing the Cell Cycle Checkpoint Regulation

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Distant metastasis is one of the major problems in treatment for advanced colorectal cancer. There is growing evidence that Polysaccharide-K (PSK), or Krestin (Sankyo Co., Tokyo, Japan), a mushroom ingredient, prevents distant metastases and improves survival rates by 10 to 20% in colorectal, gastric, esophageal, nasopharynx, lung, and breast cancers. We set out to investigate the possible role of PSK-related markers in predicting distant metastasis and the clinical outcome in colorectal cancer (CRC) patients. To screen PSK-related markers, we analyzed expression profiles using protein microarrays in a human colorectal adenocarcinoma cell line, SW480 with a mutant p53gene, and their clinical implication on the prognosis of CRC patients (n=35). We screened ECA39 protein, a direct target for c-Myc regulation, as a candidate relating to anti-metastatic effects of PSK. In immunohistochemistry, ECA39 was significantly expressed in the tumor tissues with distant metastases compared to the ones without metastases (p<0.00001). Positive ECA39 expression showed high reliability for the prediction of distant metastases (sensitivity : 86.7%, specificity : 90%, positive predictive value : 86.7%, and negative predictive value 90%). The cumulative 5-year disease free survival rate was 76% in the ECA39(-) group and 26% in the ECA39(+) group (p<0.05). Our results suggest that ECA39 is a dominant predictor of distant metastasis in patients with advanced CRC and may be useful for the application of immunotherapy by integrated medicine.