Gene-Expression Profiling Predicts Recurrence in Dukes’ C Colorectal Cancer

Arango, Diego; Laiho, Päivi; Kokko, Antti; Alhopuro, Pia; Sammalkorpi, Heli; Salovaara, Reijo; Nicorici, Daniel; Hautaniemi, Sampsa; Alazzouzi, Hafid; Mecklin∥, Jukka–Pekka; Järvinen, Heikki; Hemminki, Akseli; Astola, Jaakko; Schwartz, Simó; Aaltonen, Lauri A.

doi:10.1053/j.gastro.2005.06.066

Cited by 116 publications

(98 citation statements)

References 49 publications

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“…The results of these supplementary analyses suggest a moderate influence of the length of the PS and the choice of classifier on PP performance. The main originality of the present study is to have considered non-neoplastic mucosa samples for gene expression profiling, instead of tumor samples (Wang et al, 2004;Arango et al, 2005;Barrier et al, 2006). Non-neoplastic colonic mucosa gene expression profiles have already been studied, but only to compare them to tumor profiles (Alon et al, 1999;Kitahara et al, 2002;Notterman et al, 2002;Zou et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Prognosis of stage II colon cancer by non-neoplastic mucosa gene expression profiling

et al. 2006

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We have assessed the possibility to build a prognosis predictor (PP), based on non-neoplastic mucosa microarray gene expression measures, for stage II colon cancer patients. Non-neoplastic colonic mucosa mRNA samples from 24 patients (10 with a metachronous metastasis, 14 with no recurrence) were profiled using the Affymetrix HGU133A GeneChip. Patients were repeatedly and randomly divided into 1000 training sets (TSs) of size 16 and validation sets (VS) of size 8. For each TS/VS split, a 70-gene PP, identified on the TS by selecting the 70 most differentially expressed genes and applying diagonal linear discriminant analysis, was used to predict the prognoses of VS patients. Mean prognosis prediction performances of the 70-gene PP were 81.8% for accuracy, 73.0% for sensitivity and 87.1% for specificity. Informative genes suggested branching signal-transduction pathways with possible extensive networks between individual pathways. They also included genes coding for proteins involved in immune surveillance. In conclusion, our study suggests that one can build an accurate PP for stage II colon cancer patients, based on non-neoplastic mucosa microarray gene expression measures.

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Section: Discussionmentioning

confidence: 99%

Prognosis of stage II colon cancer by non-neoplastic mucosa gene expression profiling

et al. 2006

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“…Eight of these were fresh-frozen, had sufficient quality RNA and were assayed using Affymetrix HG-U133A expression microarrays containing 22 283 probe sets. As a comparison group, expression array data set from 29 identically processed age-, sexand grade-matched conventional CRCs from the same sample collections was utilized (Arango et al, 2005;unpublished data). Strikingly, gene expression profiling using unsupervised hierarchical clustering with a list of 7928 probes that were expressed in at least 29 of the 37 samples showed a clear distinction between the serrated and the conventional CRCs, as all but one of the eight serrated samples clustered in a single branch in the hierarchical structure (P ¼ 7.8 Â 10 À7 , Fisher's exact test).…”

Section: Expression Microarray Analysesmentioning

confidence: 99%

“…Seven out of the eight had metastasized at the time of diagnosis. As a comparison set, we used expression microarray data from 29 age-, sex-and grade-matched conventional Dukes C CRCs from the same population-based series processed identically and in tandem with the serrated samples (Arango et al, 2005; unpublished data) ( Table 1). Five of the serrated CRCs were located in the proximal and three in the distal colon, whereas nine of the conventional CRCs were located in the proximal and 20 in the distal colon.…”

Section: Patient Materialsmentioning

confidence: 99%

Serrated carcinomas form a subclass of colorectal cancer with distinct molecular basis

et al. 2006

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Serrated colorectal carcinomas (CRCs) are morphologically different from conventional CRCs and have been proposed to follow a distinct pathway of CRC formation. Despite studies of single molecular events in this tumor type, the diagnosis of serrated CRC relies on morphology and the putative unique biological character of these tumors has not been established. Here we show that the gene expression profiling of 37 CRCs separated serrated and conventional CRCs into two distinct branches in unsupervised hierarchical clustering (P-value 7.8 Â 10 À7 ), and revealed 201 differentially expressed genes representing potential biomarkers for serrated CRC. Immunohistochemistry was utilized to verify the key findings in the 37 CRCs examined by expression profiling, and a separate validation set of 37 serrated and 86 conventional CRCs was examined to evaluate the candidate biomarkers in an extended sample material. Ephrin receptor B2, hypoxia-inducible factor 1-alpha and patched appeared as proteins important for genesis of serrated CRC. This study establishes serrated CRCs as a biologically distinct subclass of CRC and represents a step forward in the molecular classification of these cancers. The study also provides a platform to understand the molecular basis of serrated CRC and in long term may contribute to the development of specific treatment options for this tumor type.

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“…The present study examined a larger number of patients and the predictive accuracy was higher in comparison with a previous report. 11 Prediction of recurrence is important in determining the treatment modality in colorectal cancer patients after surgery. Patients at high risk for developing recurrence may need intensive follow-up as well as adjuvant chemotherapy.…”

Section: Discussionmentioning

confidence: 99%