Effectiveness of Gene Expression Profiling for Response Prediction of Rectal Adenocarcinomas to Preoperative Chemoradiotherapy

Abstract

Our results suggest that pretherapeutic gene expression profiling may assist in response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy. The implementation of gene expression profiles for treatment stratification and clinical management of cancer patients requires validation in large, independent studies, which are now warranted.

Inhibitory effects of oxaliplatin in experimental radiation treatment of colorectal carcinoma: does oxaliplatin improve 5-fluorouracil-dependent radiosensitivity?

“…An accuracy rate of 95% in a subset of 7 poor responders and 12 good responders using LOOCV was detected, and furthermore, using a prediction model based on these 19 patients, an 85% accurate prediction was found in a testing set of 47 patients consisting of patients having intermediate or good pathological responses (TRG 1-3). This is comparable to what has been found for gene expression analysis (71,(99)(100)(101) as prediction accuracies of 81%, 83%, 87%, and 89% by use of subsets of discriminating genes between responders and poor responders as assessed by tumor regression grade (TRG) or T-level downstaging was observed. Multiplex kinase activity is, therefore, a promising new tool in predicting response to preoperative chemoradiotherapy in rectal cancer.…”

“…With LOOCV, one sample is left out and the remaining samples are used to build a classifier, which is then used to classify the left out sample. The fraction of samples that are classified correctly provides unbiased estimates of prediction error (71). Initially, all 8 poor responders were used in the training set, however, the single TRG 5 patient was classified as good responder, and to obtain a robust classifier we chose to exclude this sample from further analysis.…”

“…CRT delays surgery by several months, is expensive, has acute and long-term side effects, and may increase perioperative morbidity (36,48,70), thus, the possibility to predict response either before or in the early stages of treatment may spare poorly responding patients from undergoing treatment that is not beneficial. Patients with no response after CRT might probably go straight to surgery omitting CRT or be candidates for alternative or more intensive CRT regimens (71), and patients with a complete remission would benefit from omitting surgery (72). At present, no reliable technique (radiological or clinical) for predicting tumor response after CRT is available (42,73), and it has been concluded that pre-treatment T stage, N stage, histological grade, differentiation, age and gender do not reliably predict histological response to CRT (70).…”

Parallel Analysis of Transcript and Translation Profiles: Identification of Metastasis-Related Signal Pathways Differentially Regulated by Drug and Genetic Modifications

“…Prolonged exposure to caffeine, starting from weaning or from 60 days of age significantly decreased lung metastases in the PyMT transgenic mouse by 55% and 31% respectively, while introduction of the DBA/2J genome by breeding suppressed metastases by 90% (Table 1). Work from other labs has demonstrated that gene expression patterns of the primary tumors are able to predict metastatic capacity and chemotherapeutic efficiency both in animal models and in clinical trials (16)(17)(18)(19). To identify genes that were transcriptionally responsive to caffeine treatment, and were differentially regulated as a consequence of hereditary variations, gene expression patterns of the genetically or chemically modified primary tumors were analyzed using Affymetrix microarray.…”

Combined analysis of VEGF and EGFR predicts complete tumour response in rectal cancer treated with preoperative radiotherapy

“…Recently, microarray gene expression profiling was successfully used to predict complete responses to preoperative chemoradiotherapy with advanced-stage rectal cancer (Ghadimi et al, 2005;Kim et al, 2007). Epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), the p53 tumour suppressor and key mediators of cell-cycle arrest (p21, p27) and apoptosis (Bcl-2, apoptosis protease-activating factor-1 (APAF-1)) are among the immunohistochemical protein markers currently of interest as potential predictors of pathologic response, prognosis and recurrence-free survival in rectal cancer following neoadjuvant therapy (Giralt et al, 2005(Giralt et al, , 2007Lopez-Crapez et al, 2005;Kim et al, 2006;Lin et al, 2006;Smith et al, 2006;Bertolini et al, 2007).…”