Stage II Colon Cancer Prognosis Prediction by Tumor Gene Expression Profiling

Abstract

Microarray gene expression profiling is able to predict the prognosis of stage II colon cancer patients. The present study also illustrates the usefulness of resampling techniques for honest performance assessment of microarray-based PPs.

RETRACTED: A genomic approach to colon cancer risk stratification yields biologic insights into therapeutic opportunities

“…The primary goal of improved prognosis, and in particular, the ability to identify patients at high risk for recurrence, is the capacity to identify those patients in need of more effective therapy. Although others have used gene expression data to predict prognosis in colon cancer, none have validated their models in a robust manner nor have any linked the gene expression data to therapeutic strategies (16)(17)(18)(19). Using gene expression methodologies to understand the molecular mechanisms involved in cancer progression may be helpful beyond prognosis because this knowledge may lead to the study of drugs that target relevant, deregulated pathways in an individual patient.…”

Dysregulation of the transcription factors SOX4, CBFB and SMARCC1 correlates with outcome of colorectal cancer

“…Notably, this association was only observed in our MSS series (Table 2), consistent with SOX4 being differentially expressed between MSS and MSI tumours (Table 2). In the validation data set from Barrier et al (2006), SOX4 expression in the upper tertile was also associated with a significantly higher incidence (P ¼ 0.005, Fisher's exact test) of recurrence and a shorter recurrence-free survival (log-rank test P ¼ 0.0092 and univariate cox regression analysis P ¼ 0.01; hazard ratio 2.7; 95% CI, 1.2 -6.0). Recurrence-free survival as a function of SOX4 expression is plotted in Figure 2B.…”

“…The higher number of candidates associated with recurrence of MSI cancer may be caused by a higher false-positive rate due to the limited number of samples in the MSI series (9 recurrent and 56 non-recurrent) compared with the MSS series (22 recurrent and 173 nonrecurrent). The availability of transcriptional profiles from an independent cohort of stage II MSS cancer patients (Barrier et al, 2006) enabled us to investigate if any of the three MSS candidates could be validated. To our knowledge, no such data set is public available for MSI cancer; hence, the MSI candidates still await validation.…”

“…Unpaired t-tests indicated that three of the 51 TFs were significantly associated (Po0.05) with recurrence of stage II MSS cancer and 13 with recurrence of MSI stage II cancer (Table 2 and Supplementary Table 7). From a recent report we extracted Affymetrix HG_U133A transcriptional profiles of 25 non-recurrence and 25 recurrence (liver metastases) stage II MSS colon cancers (Barrier et al, 2006). By analysing this independent data set one of the three significant TFs (SOX4) from our MSS series was validated (P ¼ 0.0039, unpaired t-test).…”

“…To enable survival analysis, the SOX4 expression data were dichotomised with the highest tertile classified as high and the lower two tertiles classified as low. This cutoff was set based on associations within the MSS stage II CRC cohort of this study before analysing the validation cohort from Barrier et al (2006). As expected, the patients having an SOX4 expression level in the highest tertile experienced a significantly higher incidence of recurrence (P ¼ 0.005, w 2 test) and a shorter recurrence-free survival (Figure 2A, log-rank test P ¼ 0.0083 and univariate cox regression analysis P ¼ 0.01; hazard ratio 2.0; 95% CI, 1.18 -3.51).…”