A Hallmark-Based Six-Gene Expression Signature to Assess Colorectal Cancer and Its Recurrence Risk.

Abstract

Purpose: As part of the effort to establish a general profile for solid tumors, the aim of this study was to develop a real-time polymerase chain reaction (RT-PCR)-based assay to assess colorectal cancer (CRC) and its recurrence risk utilizing the limited amounts of tissues available from biopsies through colonoscopy. Materials and Methods: Six candidate genes, reflecting the hallmarks of cancer cells, were identified by analyzing the gene expression profiles of primary invasive tumors in the public database. The expression of these genes in CRC and noncancerous colon tissues was quantified by RT-quantitative PCR. Classifiers were then generated to distinguish the tumors from the normal colon tissues, and to assess the risk of CRC recurrence based on the disease-free survival time, overall survival time, and metastatic status of the patients. Results: The expression profile of a five-gene panel was utilized to build a model that is capable of distinguishing CRC cancer tissues from noncancerous colorectal tissues (p < 0.0001). A classifier based on the expression signature of four genes, three of which were included in the five-gene panel, was then developed for assessing the tumor recurrence risk. This classifier could correctly identify those with a poor likelihood of survival (high risk of recurrence) >80% of time. There was a significant difference in disease-free survival time between patients in the low recurrence group and those in the high-risk group. Conclusion: The expression signatures of the six genes that reflect the genetic hallmarks of cancer cells could serve as a biomarker for identifying CRC and assessing the risk of recurrence with high sensitivity and specificity.