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


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


METHODS
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.


CONCLUSIONS
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.
1 Department of Surgery, Division of Colon and Rectal Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea 2 Department of Colorectal and Endoscopic Surgery, I.M. Sechenov First Moscow State Medical University, Moscow, Russia 3 Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea 4 Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea 5 Department of Medical Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Hyuk
H
Hur
Inna
I
Tulina
Min Soo
MS
Cho
Byung Soh
BS
Min
Woong Sub
WS
Koom
Joon Seok
JS
Lim
Joong Bae
JB
Ahn
Nam Kyu
NK
Kim
D000071916:AC133 Antigen / Q000032:analysis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D057234:Preoperative Period; D011379:Prognosis; D012004:Rectal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000628:therapy; D015203:Reproducibility of Results; D056910:Republic of Korea; D012107:Research Design; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics
D000071916:AC133 Antigen; D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53