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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 13/2019

01-12-2019 | Translational Research and Biomarkers

Comprehensive Exploration to Identify Predictive DNA Markers of ΔNp63/SOX2 in Drug Resistance in Human Esophageal Squamous Cell Carcinoma

Authors: Yosuke Ooizumi, MD, Keita Kojima, MD, Kazuharu Igarashi, MD, Yoko Tanaka, MD, Hiroki Harada, MD, Kazuko Yokota, MD, Takeshi Kaida, MD, Satoru Ishii, MD, PhD, Toshimichi Tanaka, MD, PhD, Keigo Yokoi, MD, PhD, Nobuyuki Nishizawa, MD, PhD, Marie Washio, MD, Hideki Ushiku, MD, PhD, Hiroshi Katoh, MD, PhD, Yoshimasa Kosaka, MD, PhD, Hiroaki Mieno, MD, PhD, Kei Hosoda, MD, PhD, Masahiko Watanabe, MD, PhD, FACS, Chikatoshi Katada, MD, PhD, Naoki Hiki, MD, PhD, Keishi Yamashita, MD, PhD, FACS

Published in: Annals of Surgical Oncology | Issue 13/2019

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Abstract

Background

OBP-801 is a novel histone deacetylase inhibitor being developed as an anticancer drug. In this study, we explored genes to predict drug resistance in human cancer.

Methods

OBP-801 resistance was assessed in 37 strains of human cancer cell lines. Expression microarrays harboring 54,675 genes were used to focus on candidate genes, which were validated for both functional and clinical relevance in esophageal squamous cell carcinoma (ESCC).

Results

OBP-801 is sensitive to esophageal, gastric, and thyroid cancer, and resistant to some esophageal and colorectal cancers. We therefore used ESCC to explore genes. Comprehensive exploration focused on ΔNp63/SOX2, which were both genetically and epigenetically overexpressed in ESCC. Genomic amplifications of ΔNp63/SOX2 were tightly correlated each other (r = 0.81). Importantly, genomic amplification of ΔNp63/SOX2 in the resected tumors after neoadjuvant chemotherapy was significantly associated with histological grade of response (G1). Forced expression of either of these two genes did not induce each other, suggesting that their functional relevances were independent and showed robust drug resistance in OBP-801, as well as 5-fluorouracil. Furthermore, ΔNp63 could exert a potent oncogenic potential. RNA interference of ΔNp63 supported its oncological properties, as well as drug resistance.

Conclusion

Comprehensive exploration of genes involved in anticancer drug residence could identify critical oncogenes of ΔNp63/SOX2 that would predict chemotherapy response in ESCC.
Appendix
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Metadata
Title
Comprehensive Exploration to Identify Predictive DNA Markers of ΔNp63/SOX2 in Drug Resistance in Human Esophageal Squamous Cell Carcinoma
Authors
Yosuke Ooizumi, MD
Keita Kojima, MD
Kazuharu Igarashi, MD
Yoko Tanaka, MD
Hiroki Harada, MD
Kazuko Yokota, MD
Takeshi Kaida, MD
Satoru Ishii, MD, PhD
Toshimichi Tanaka, MD, PhD
Keigo Yokoi, MD, PhD
Nobuyuki Nishizawa, MD, PhD
Marie Washio, MD
Hideki Ushiku, MD, PhD
Hiroshi Katoh, MD, PhD
Yoshimasa Kosaka, MD, PhD
Hiroaki Mieno, MD, PhD
Kei Hosoda, MD, PhD
Masahiko Watanabe, MD, PhD, FACS
Chikatoshi Katada, MD, PhD
Naoki Hiki, MD, PhD
Keishi Yamashita, MD, PhD, FACS
Publication date
01-12-2019
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 13/2019
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-019-07795-w

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