RNA expression of the molecular signature genes for metastasis in colorectal cancer.

Abstract

Colorectal cancer is an endemic disease in the western world. Search for molecular signatures present in primary tumors that predict tumor metastasis potential has been proposed and in particular, a 17-gene molecular signature is associated with poor survival in breast cancer, prostate cancer, meduloblastoma and lymphoma in a recent study. Using quantitative real-time PCR assay (qPCR), our study observed tumor-normal differential RNA expression in 15 of these 17 genes in a cohort of 52 stage III colorectal cancer patients (all p<0.05), which signified the importance of these 17 signature genes in colorectal cancer. Although no significant correlation was found between tumor RNA levels of these 17 genes and some of clinical features (age, gender, and location, all p>0.05), two distinct groups among these genes were observed with Spearman correlation scores>0.6 (p<0.01), suggesting co-expression/interaction within these genes. Of the 37 patients for whom complete follow-up data was available, 12 patients had recurrence and 25 had no recurrence. There was no significant difference in tumor RNA levels between recurrence and non-recurrence groups for the 17 genes (all p>0.05), but the recurrence group had more patients with mucinous tumors (9/12 vs. 7/25, p<0.05) and more lymph node involvement (median 7.2 vs. 2.5, p<0.05) compared to the non-recurrence group. Moreover, survival analysis revealed a significant difference in patient overall survival time between low and high tumor RNA levels for 1 of the 17 genes (PTTG1, p=0.024). Our qPCR validation study confirms the importance of most 17-gene molecular signature genes with differential RNA expression and suggests the relevance of PTTG1 for survival in colorectal cancers.