LRP1 expression in colon cancer predicts clinical outcome.

UNLABELLED

LRP1 (low-density lipoprotein receptor-related protein 1), a multifunctional endocytic receptor, has recently been identified as a hub within a biomarker network for multi-cancer clinical outcome prediction. As its role in colon cancer has not yet been characterized, we here investigate the relationship between LRP1 and outcome.

MATERIALS AND METHODS

mRNA expression was determined in colon adenocarcinoma and paired colon mucosa samples, as well as in stromal and tumor cells obtained after laser capture microdissection. Clinical potential was further investigated by immunohistochemistry in a population-based colon cancer series ( = 307). methylation, mutation and miR-205 expression were evaluated and compared with LRP1 expression levels.

RESULTS

mRNA levels were significantly lower in colon adenocarcinoma cells compared with colon mucosa and stromal cells obtained after laser capture microdissection. Low LRP1 immunohistochemical expression in adenocarcinomas was associated with higher age, right-sided tumor, loss of CDX2 expression, Annexin A10 expression, CIMP-H, MSI-H and V600E mutation. Low LRP1 expression correlated with poor clinical outcome, especially in stage IV patients. While LRP1 expression was downregulated by mutation, promoter was never methylated.

CONCLUSIONS

Loss of LRP1 expression is associated with worse colon cancer outcomes. Mechanistically, mutation modulates LRP1 expression.