Abstract
We evaluated the clinical benefits of novel predictive markers for distant recurrence with colorectal cancer using lectin microarray analysis of cell surface glycan modifications. Glycoproteins were extracted from formalin-fixed, paraffin-embedded tumor specimens and normal epithelium from 53 consecutive curatively resected stage I–III colorectal cancer cases and then subjected to lectin microarray to obtain lectin–glycan interaction (LGI) values. In addition, clinicopathological factors associated with distant recurrence were identified. LGI values that were associated with distant recurrence were validated with an additional 55 curatively resected stage II colorectal cancer cases. LGI values for Agaricus bisporus (ABA) lectin, prominent in cancer tissues, were statistically associated with distant recurrence. ABA lectin staining exhibited strikingly intense signals in the cytoplasm and apical surfaces of cancer cells, while weak staining was observed in the supranuclear regions of normal epithelium. This ABA tumor/normal LGI ratio may be a new predictive biomarker for distant recurrence of curatively resected colorectal cancer.
Highlights
Colorectal cancer is a major cause of morbidity and mortality, with a worldwide annual incidence that ranks third among men (746,000 cases; 10.0% of total cancers per year) and second among women (614,000 cases; 9.2%) [1]
We evaluated multiple glycan expression profiles using a lectin microarray system for the tissues of curatively treated subjects, to identify predictive markers for distant colorectal cancer recurrence
The clinicopathological factors and 45 lectins in two independent cohorts showed that an increased ABA-binding signal could be a predictive factor for distant colorectal cancer recurrence (Figs. 2A and 3)
Summary
Colorectal cancer is a major cause of morbidity and mortality, with a worldwide annual incidence that ranks third among men (746,000 cases; 10.0% of total cancers per year) and second among women (614,000 cases; 9.2%) [1]. Adjuvant chemotherapy after complete tumor resection is effective for reducing the recurrence risk [2,3,4]. Determining the optimal indications for adjuvant chemotherapy, minimizing the side effects, and decreasing the risk of recurrence are important goals. Investigators have attempted to identify predictive factors other than the pathological stage for colorectal cancer recurrence. Both oncogenes, such as c-myc, TGF-b, BRAF, and p53, and clinicopathological factors, including lymphatic or venous invasion and budding [6], reportedly predicted recurrence; to date, none of these proved to be statistically reliable as predictive factors for use in clinical practice [7].
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