For Stage II colon cancer patients, the benefits of chemotherapy do not clearly outweigh the associated morbidity from adverse events. The majority of patients with stage II disease in Europe and the Americas therefore do not receive adjuvant chemotherapy after surgery. Unfortunately, 25-30% of stage II colon cancer patients relapse and die from metastatic disease within 6 years. Our team has recently developed a sensitive, reproducible and cost effective assay technology (DASL) that can generate high quality RNA expression profiles from routinely collected formalin fixed paraffin embedded (FFPE) tissue specimens. Our team has also recently identified gene expression signatures associated with metastatic potential (in prostate cancer), has significant experience in the successful design and application of novel gene arrays, and has substantial numbers of FFPE specimens from Stage II colon cancer patients with well characterized metastatic recurrence, progression free survival and other clinical outcome data. We therefore propose:
SPECIFIC AIM 1 : To identify a gene expression signature that can predict which stage II colon cancer patients relapse and die from metastatic disease. We will profile metastasis genes in tumors from 120 stage II colon cancer patients with and without metastatic recurrence using a novel Illumina DASL oligonucleotide bead array (DASL- Colon Recurrent Cancer;DASL-CRC).
SPECIFIC AIM 2 : To validate the DASL-CRC stage II colon cancer metastasis signature. We will test the hypothesis that the DASL-CRC signature generated in Aim 1 can correctly identify in a second, non-overlapping set of 120 tumors the stage II colon cancer patients who die from metastatic relapse. In summary, this project will use state of the art technology to discover and validate an FFPE gene expression profile that accurately predicts the subset of Stage II patients who are most likely to die from recurrent disease, and who therefore are most likely to benefit from adjuvant chemotherapy.
For Stage II colon cancer patients, the benefits of chemotherapy do not clearly outweigh the associated morbidity from adverse events. This proposal seeks to identify a molecular signature of metastasis to help identify those patients who will benefit most from chemotherapy.
