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Diseases of the Colon & Rectum
Published in: Diseases of the Colon & Rectum 9/2007

01-09-2007

Microarray Gene Expression Profiling for Predicting Complete Response to Preoperative Chemoradiotherapy in Patients with Advanced Rectal Cancer

Authors: Il-Jin Kim, Ph.D., Seok-Byung Lim, M.D., Hio Chung Kang, Ph.D., Hee Jin Chang, M.D., Sun-A Ahn, B.S., Hye-Won Park, M.S., Sang-Geun Jang, B.S., Jae-Hyun Park, M.S., Dae Yong Kim, M.D., Kyung Hae Jung, M.D., Hyo Seong Choi, M.D., Seung-Yong Jeong, M.D., Dae Kyung Sohn, M.D., Duck-Woo Kim, M.D., Jae-Gahb Park, M.D., Ph.D.

Published in: Diseases of the Colon & Rectum | Issue 9/2007

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Purpose

Preoperative chemoradiotherapy is widely used to improve local control and sphincter preservation in patients with locally advanced rectal cancer. In the present study, we investigated whether microarray gene expression analysis could predict complete response to preoperative chemoradiotherapy in rectal cancer.

Methods

Tumor tissues were obtained from 46 patients with rectal cancer (31 for training and 15 for validation testing). All patients underwent preoperative chemoradiotherapy involving 50.4 gray radiotherapy, followed by surgical excision 6 weeks later. Response to chemoradiotherapy was evaluated according to Dworak’s tumor regression grade. Tumor regression Grades 1, 2, and 3 were considered partial responses, and tumor regression Grade 4 was considered a complete response. By using the 31 training samples, genes differentially expressed between partial response and complete response were identified, and clustering analysis was performed. Prediction analysis of response to chemoradiotherapy was performed on the 31 training samples by using a selected set of 95 “predictor” genes. Those findings were validated by independent analysis of the 15 test samples.

Results

The 31 training samples comprised 20 partial response and 11 complete response cases. A primary set of 261 genes was identified as differentiating between partial response and complete response. By supervised clustering using these 261 genes, 30 of 31 training samples were clustered correctly according to tumor response. A gene set comprising the top-ranked 95 genes displaying differential expression between partial response and complete response was applied to predict response to chemoradiotherapy. Complete response and partial response were accurately predicted in 84 percent (26/31) of training samples and 87 percent (13/15) of validation samples.

Conclusions

Microarray gene expression analysis was successfully used to predict complete responses to preoperative chemoradiotherapy in patients with advanced rectal cancer.
Literature
1.
Kapiteijn, E Marijnen, CA Nagtegaal, ID Dutch Colorectal Cancer Group et al. 2001Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancerN Engl J Med345638646PubMedCrossRef
2.
Sauer, R Becker, H Hohenberger, W German Rectal Cancer Study Group et al. 2004Preoperative versus postoperative chemoradiotherapy for rectal cancerN Engl J Med35117311740PubMedCrossRef
3.
Ruo, L, Tickoo, S, Klimstra, DS,  et al. 2002Long-term prognostic significance of extent of rectal cancer response to preoperative radiation and chemotherapyAnn Surg2367581PubMedCrossRef
4.
Garcia-Aguilar, J, Hernandez de Anda, E, Sirivongs, P, Lee, SH, Madoff, RD, Rothenberger, DA 2003A pathologic complete response to preoperative chemoradiation is associated with lower local recurrence and improved survival in rectal cancer patients treated by mesorectal excisionDis Colon Rectum46298304PubMedCrossRef
5.
Kim, DW, Lim, SB, Kim, DY,  et al. 2006Preoperative chemoradiotherapy improves surgical sphincter preservation in patients with rectal cancer located within 3 cm of the anal vergeEur J Surg Oncol32162167PubMedCrossRef
6.
Ortholan, C, Francois, E, Thomas, O,  et al. 2006Role of radiotherapy with surgery for T3 and resectable T4 rectal cancer: evidence from randomized trialsDis Colon Rectum49302310PubMedCrossRef
7.
Kim, DW, Kim, DY, Kim, TH,  et al. 2006Is T classification still correlated with lymph node status after preoperative chemoradiotherapy for rectal cancer?Cancer10616941700PubMedCrossRef
8.
Barratt, PL, Seymour, MT, Stenning, SP,  et al. 2002UKCCCR AXIS trial collaborators. Adjuvant X-ray and Fluorouracil Infusion Study. DNA markers predicting benefit from adjuvant fluorouracil in patients with colon cancer: a molecular studyLancet36013811391PubMedCrossRef
9.
Buess, M, Terracciano, L, Reuter, J,  et al. 2004STRAP is a strong predictive marker of adjuvant chemotherapy benefit in colorectal cancerNeoplasia6813820PubMedCrossRef
10.
Allegra, CJ, Paik, S, Colangelo, LH,  et al. 2003Prognostic value of thymidylate synthase, Ki-67, and p53 in patients with Dukes’ B and C colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project collaborative studyJ Clin Oncol21241250PubMedCrossRef
11.
Watanabe, T, Wu, TT, Catalano, PJ,  et al. 2001Molecular predictors of survival after adjuvant chemotherapy for colon cancerN Engl J Med34411961206PubMedCrossRef
12.
Kang, HC, Kim, IJ, Park, JH,  et al. 2004Identification of genes with differential expression in acquired drug-resistant gastric cancer cells using high-density oligonucleotide microarraysClin Cancer Res10272284PubMedCrossRef
13.
Rau, B, Sturm, I, Lage, H,  et al. 2003Dynamic expression profile of p21WAF1/CIP1 and Ki-67 predicts survival in rectal carcinoma treated with preoperative radiochemotherapyJ Clin Oncol2133913401PubMedCrossRef
14.
Mariadason, JM, Arango, D, Shi, Q,  et al. 2003Gene expression profiling-based prediction of response of colon carcinoma cells to 5-fluorouracil and camptothecinCancer Res6387918812PubMed
15.
Golub, TR, Slonim, DK, Tamayo, P,  et al. 1999Molecular classification of cancer: class discovery and class prediction by gene expression monitoringScience286531537PubMedCrossRef
16.
Kim, IJ, Kang, HC, Park, JG 2004Microarray applications in cancer researchCancer Res Treat36207213CrossRefPubMed
17.
Pomeroy, SL, Tamayo, P, Gaasenbeek, M,  et al. 2002Prediction of central nervous system embryonal tumour outcome based on gene expressionNature415436442PubMedCrossRef
18.
Ghadimi, BM, Grade, M, Difilippantonio, MJ,  et al. 2005Effectiveness of gene expression profiling for response prediction of rectal adenocarcinomas to preoperative chemoradiotherapyJ Clin Oncol2318261838PubMedCrossRef
19.
Watanabe, T, Komuro, Y, Kiyomatsu, T,  et al. 2006Prediction of sensitivity of rectal cancer cells in response to preoperative radiotherapy by DNA microarray analysis of gene expression profilesCancer Res6633703374PubMedCrossRef
20.
Greene, FL, Page, DL, Fleming, ID,  et al. 2002AJCC cancer staging manual6thSpringer-VerlagNew York
21.
Dworak, O, Keilholz, L, Hoffmann, A 1997Pathological features of rectal cancer after preoperative radiochemotherapyInt J Colorectal Dis121923PubMedCrossRef
22.
Kim, IJ, Kang, HC, Jang, SG,  et al. 2006Oligonucleotide microarray analysis of distinct gene expression patterns in colorectal cancer tissues harboring BRAF and K-ras mutationsCarcinogenesis27392404PubMedCrossRef
23.
Eisen, MB, Spellman, PT, Brown, PO, Botstein, D 1998Cluster analysis and display of genome-wide expression patternsProc Natl Acad Sci USA951486314868PubMedCrossRef
24.
Wang, Y, Jatkoe, T, Zhang, Y,  et al. 2004Gene expression profiles and molecular markers to predict recurrence of Dukes’ B colon cancerJ Clin Oncol2215641571PubMedCrossRef
25.
Response assessment of nonsurgical treatment for colorectal carcinoma. Japanese classification of colorectal carcinoma. Japanese Society for Cancer of the Colon and Rectum. 1st English ed. Tokyo: Kanehara & Co, 1997:77–82
26.
Staunton, JE, Slonim, DK, Coller, HA,  et al. 2001Chemosensitivity prediction by transcriptional profilingProc Natl Acad Sci USA981078710792PubMedCrossRef
27.
Edler, D, Glimelius, B, Hallstrom, M,  et al. 2002Thymidylate synthase expression in colorectal cancer: a prognostic and predictive marker of benefit from adjuvant fluorouracil-based chemotherapyJ Clin Oncol2017211728PubMedCrossRef
28.
Johnston, PG, Fisher, ER, Rockette, HE,  et al. 1994The role of thymidylate synthase expression in prognosis and outcome of adjuvant chemotherapy in patients with rectal cancerJ Clin Oncol1226402647PubMed
29.
Angelis, PM, Fjell, B, Kravik, KL,  et al. 2004Molecular characterizations of derivatives of HCT116 colorectal cancer cells that are resistant to the chemotherapeutic agent 5-fluorouracilInt J Oncol2412791288PubMed
30.
Otomo, T, Hishii, M, Arai, H, Sato, K, Sasai, K 2004Microarray analysis of temporal gene responses to ionizing radiation in two glioblastoma cell lines: up-regulation of DNA repair genesJ Radiat Res (Tokyo)455360CrossRef
31.
Kitahara, O, Katagiri, T, Tsunoda, T, Harima, Y, Nakamura, Y 2002Classification of sensitivity or resistance of cervical cancers to ionizing radiation according to expression profiles of 62 genes selected by cDNA microarray analysisNeoplasia4295303PubMedCrossRef
32.
Shimizu, D, Ishikawa, T, Ichikawa, Y,  et al. 2005Prediction of chemosensitivity of colorectal cancer to 5-fluorouracil by gene expression profiling with cDNA microarraysInt J Oncol27371376PubMed
Metadata
Title
Microarray Gene Expression Profiling for Predicting Complete Response to Preoperative Chemoradiotherapy in Patients with Advanced Rectal Cancer
Authors
Il-Jin Kim, Ph.D.
Seok-Byung Lim, M.D.
Hio Chung Kang, Ph.D.
Hee Jin Chang, M.D.
Sun-A Ahn, B.S.
Hye-Won Park, M.S.
Sang-Geun Jang, B.S.
Jae-Hyun Park, M.S.
Dae Yong Kim, M.D.
Kyung Hae Jung, M.D.
Hyo Seong Choi, M.D.
Seung-Yong Jeong, M.D.
Dae Kyung Sohn, M.D.
Duck-Woo Kim, M.D.
Jae-Gahb Park, M.D., Ph.D.
Publication date
01-09-2007
Publisher
Springer-Verlag
Published in
Diseases of the Colon & Rectum / Issue 9/2007
Print ISSN: 0012-3706
Electronic ISSN: 1530-0358
DOI
https://doi.org/10.1007/s10350-007-277-7

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