Gene‐expression signature of tumor recurrence in patients with stage II and III colon cancer treated with 5′fluoruracil‐based adjuvant chemotherapy

Abstract

Although receiving adjuvant chemotherapy after radical surgery, a disappointing proportion of patients with colorectal cancer will develop tumor recurrence. Probability of relapse is currently predicted from pathological staging, there being a need for additional markers to further select high-risk patients. This study was aimed to identify a gene-expression signature to predict tumor recurrence in patients with Stages II and III colon cancer treated with 5 0 fluoruracil (5FU)-based adjuvant chemotherapy. Two-hundred and twenty-eight patients diagnosed with Stages II-III colon cancer and treated with surgical resection and 5FU-based adjuvant chemotherapy were included. RNA was extracted from formalin-fixed, paraffin-embedded tissue samples and expression of 27 selected candidate genes was analyzed by RT-qPCR. A tumor recurrence predicting model, including clinico-pathological variables and gene-expression profiling, was developed by Cox regression analysis and validated by bootstrapping. The regression analysis identified tumor stage and S100A2 and S100A10 gene expression as independently associated with tumor recurrence. The risk score derived from this model was able to discriminate two groups with a highly significant different probability of tumor recurrence (HR, 2.75; 95%CI, 1.71-4.39; p 5 0.0001), which it was maintained when patients were stratified according to tumor stage. The algorithm was also able to distinguish two groups with different overall survival (HR, 2.68; 95%CI, 1.12-6.42; p 5 0.03). Identification of a new gene-expression signature associated with a high probability of tumor recurrence in patients with Stages II and III colon cancer receiving adjuvant 5FU-based chemotherapy, and its combination in a robust, easy-to-use and reliable algorithm may contribute to tailor treatment and surveillance strategies.

Annexin A2 Heterotetramer: Structure and Function

“…Interestingly, Zhang et al [195] identified S100A10 as the major contributor to plasminogen binding, plasmin generation and subsequent invasiveness of Colo 222 colorectal cancer cells, cells which do not express surface annexin A2. Moreover, S100A10 expression correlated with tumor recurrence in stage II and III colon cancer patients treated with 5-fluoruracil [196]. Importantly, it therefore appears that the invasiveness of cancer cells observed in colorectal cancer is potentially maintained through the increased stabilization of S100A10 (and not annexin A2) as invasion can also be mediated through an annexin A2-independent manner as observed in the Colo 222 cells.…”

Tight Junction Protein Claudin-2 Promotes Self-Renewal of Human Colorectal Cancer Stem-like Cells

“…The association between CLDN2 mRNA expression and disease outcome in patients with stage II/III colorectal cancer treated with 5-FU-based chemotherapy was analyzed in three independent datasets. Quantification of CLDN2 mRNAs from paraffin-embedded sections using qRT-PCR and correlation with patient survival was performed on a cohort treated at the Hospital Clínic of Barcelona in 1998-2005 (13,14). Two other datasets were selected on the basis of the presence of CLDN2specific probes, the number of patients (>150), and the availability of recurrence-free survival data.…”

Building personalized treatment plans for early-stage colorectal cancer patients

“…Many prognostic recurrence studies have included a small number of biomarkers, such as gene [19, 25, 26], microRNA [18], or protein expression markers [21], and have had limited success. In fact, when published gene or protein markers were retested in a separate study, these markers failed to predict recurrence [21].…”