Justin Huang

In patients with metastatic colon cancer response to first line chemotherapy is a strong predictor of overall survival OS Currently oncologists lack diagnostic tests to determine which chemotherapy regimen offers the greatest chance for response in an individual patient Here we present the results of gene expression analysis for two genes ERCC1 and TS measured with the commercially available ResponseDX Colon assay Response Genetics Los Angeles CA in 41 patients with de novo metastatic colon cancer diagnosed between July 2008 and August 2013 at the University of California San Diego In addition ERCC1 and TS expression levels as determined by RNAseq and survival data for patients in TCGA were downloaded from the TCGA data portal We found that patients with low expression of ERCC1 n 33 had significantly longer median OS 36 0 vs 10 1 mo HR 0 29 95 CI 095 to 84 log-rank p 9 0x10-6 and median time to treatment to failure TTF following first line chemotherapy 14 1 vs 2 4 mo HR 0 17 95 CI 0 048 to 0 58 log-rank p 5 3x10-4 relative to those with high expression n 4 After accounting for the covariates age sex tumor grade and ECOG performance status in a Cox proportional hazard model the association of low ERCC1 with longer OS HR 0 18 95 CI 0 14 to 0 26 p 0 0448 and TTF HR 0 16 95 CI 0 14 to 0 21 p 0 0053 remained significant Patients with low TS expression n 29 had significantly longer median OS 36 0 vs 14 8 mo HR 0 25 95 CI 0 074 to 0 82 log-rank p 0 022 relative to those with high expression n 12 The combined low expression of ERCC1 TS was predictive of response in patients treated with FOLFOX 40 vs 91 RR 2 3 Fisher s exact test p 0 03 n 27 but not with FOLFIRI 71 vs 71 RR 1 0 Fisher s exact test p 1 n 14 Overall these findings suggest that measurement of ERCC1 and TS expression has potential clinical utility in managing patients with metastatic colorectal cancer

Graduate Student

Summary

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ERCC1 and TS Expression as Prognostic and Predictive Biomarkers in Metastatic Colon Cancer.

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