Biomarker-Based Scoring System for Prediction of Tumor Response After Preoperative Chemoradiotherapy in Rectal Cancer by Reverse Transcriptase Polymerase Chain Reaction Analysis

Abstract

BACKGROUND: Numerous molecular markers have been investigated to predict tumor response after preoperative chemoradiotherapy for rectal cancer.

OBJECTIVE: This study aimed to evaluate the predictive value of biomarkers for the prediction of tumor response after preoperative chemoradiotherapy.

DESIGN & SETTING: Tumor specimens have been collected prospectively from 80 patients with rectal cancer who underwent curative resection at 8 weeks after completing preoperative chemoradiotherapy.

MAIN OUTCOME MEASURES: With the use of reverse transcriptase polymerase chain reaction analysis, mRNA expression levels of 7 candidate biomarkers (p53, p21, Ki-67, VEGF, CD133, CD24, and CD44) were evaluated from fresh tumor samples collected before preoperative chemoradiotherapy. The correlation between biomarker expression levels and the pathologic response was assessed based on histopathological staging (pTNM) and tumor regression grade.

RESULTS: The mRNA expression levels of 4 biomarkers (p53, p21, Ki67, and CD133) significantly correlated with tumor regression grade response and pathologic complete response. Patients showing low expression of p53 and/or high expression of p21, Ki67, and CD133 exhibited a significantly greater tumor regression grade response and pathologic complete response rate. A scoring system devised so that 1 point was given for each biomarker whose expression level correlated with pathologic complete response (score range: 0-4) showed that 9 of 62 patients with scores of 0 to 2 achieved pathologic complete response, whereas 15 of 18 patients with scores of 3 to 4 achieved pathologic complete response (14.5% vs 83.3%, p < 0.001). For prediction of pathologic complete response, the scoring system showed 62.5% sensitivity, 94.6% specificity, an 83.3% positive predictive value, and an 85.5% negative predictive value.

LIMITATIONS: Small patient numbers have limitations related to the reproducibility and ability to provide quantitative information. In addition, this study lacks test and validation sets.

CONCLUSIONS: The pretreatment mRNA expression levels of 4 biomarkers correlated with pathologic tumor response after intraoperative chemoradiotherapy in rectal cancer. Furthermore, the scoring system combining values of biomarker expression might have predictive power with high positive and negative predictive values.