Oncotarget

Research Papers:

Correlation between tumor engraftment in patient-derived xenograft models and clinical outcomes in colorectal cancer patients

Bo Young Oh, Woo Yong Lee, Sungwon Jung, Hye Kyung Hong, Do-Hyun Nam, Yoon Ah Park, Jung Wook Huh, Seong Hyeon Yun, Hee Cheol Kim, Ho-Kyung Chun and Yong Beom Cho _

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Oncotarget. 2015; 6:16059-16068. https://doi.org/10.18632/oncotarget.3863

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Abstract

Bo Young Oh1,*, Woo Yong Lee1,2,*, Sungwon Jung3, Hye Kyung Hong1, Do-Hyun Nam2,4, Yoon Ah Park1, Jung Wook Huh1, Seong Hyeon Yun1, Hee Cheol Kim1, Ho-Kyung Chun5 and Yong Beom Cho1,2,6

1 Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

2 Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea

3 Department of Genome Medicine and Science, Graduate School of Medicine, Gachon University, Incheon, Korea

4 Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

5 Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

6 Department of Medical Device Management and Research, SAIHST, Sungkyunkwan University, Seoul, Korea

* These authors have contributed equally to this work

Correspondence to:

Yong Beom Cho, email:

Keywords: colorectal cancer, survival, xenograft, genomic profile, drug response

Received: November 20, 2014 Accepted: April 02, 2015 Published: April 18, 2015

Abstract

Despite numerous studies involving patient-derived xenograft (PDX) models, few studies have investigated the relationship between the ability of the tumor to engraft (tumorigenicity) and the clinical features of colorectal cancer (CRC). The aim of this study was to determine whether tumorigenicity correlates with clinical outcomes of CRC patients. We included 241 CRC patients who underwent radical surgery from 2010 to 2013. PDX models were established by implanting tumor fragments obtained from these patients into the subcutaneous layer of immunodeficient mice. Xenografts were successfully established from 62.2%. Successful engraftment was associated with advanced stage (p < 0.001) and moderate/poor differentiation (p = 0.029). Three-year disease-free survival (DFS) rates were lower for patients with tumorigenicity (p = 0.011). In stage III patients, tumorigenicity was an independent predictor of poor DFS (p = 0.034). In addition, mutation of TP53 was most frequently detected in stage III patients with tumorigenicity. Two models of stage IV disease without KRAS mutations showed high sensitivity to EGFR-targeted agents, while none of the models with KRAS mutations showed high sensitivity. In conclusion, PDX models may provide an effective preclinical tool for predicting cancer progression and could be used to further genomic and pharmacologic research on personalized treatments.


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