Frontiers in Oncology (Apr 2022)
Genomic and Molecular Signatures of Successful Patient-Derived Xenografts for Oral Cavity Squamous Cell Carcinoma
- Wei-Chen Yen,
- Wei-Chen Yen,
- Ian Yi-Feng Chang,
- Ian Yi-Feng Chang,
- Kai‐Ping Chang,
- Kai‐Ping Chang,
- Kai‐Ping Chang,
- Chun‐Nan Ouyang,
- Chiao-Rou Liu,
- Chiao-Rou Liu,
- Chiao-Rou Liu,
- Ting-Lin Tsai,
- Ting-Lin Tsai,
- Yi-Cheng Zhang,
- Yi-Cheng Zhang,
- Chun-I Wang,
- Ya-Hui Wang,
- Alice L. Yu,
- Alice L. Yu,
- Hsuan Liu,
- Hsuan Liu,
- Hsuan Liu,
- Hsuan Liu,
- Chih-Ching Wu,
- Chih-Ching Wu,
- Chih-Ching Wu,
- Chih-Ching Wu,
- Yu-Sun Chang,
- Yu-Sun Chang,
- Yu-Sun Chang,
- Jau-Song Yu,
- Jau-Song Yu,
- Jau-Song Yu,
- Jau-Song Yu,
- Chia-Yu Yang,
- Chia-Yu Yang,
- Chia-Yu Yang,
- Chia-Yu Yang
Affiliations
- Wei-Chen Yen
- Department of Otolaryngology Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Wei-Chen Yen
- Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
- Ian Yi-Feng Chang
- Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
- Ian Yi-Feng Chang
- Department of Neurosurgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Kai‐Ping Chang
- Department of Otolaryngology Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Kai‐Ping Chang
- Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
- Kai‐Ping Chang
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Chun‐Nan Ouyang
- Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
- Chiao-Rou Liu
- Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
- Chiao-Rou Liu
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Chiao-Rou Liu
- Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Ting-Lin Tsai
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Ting-Lin Tsai
- Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Yi-Cheng Zhang
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Yi-Cheng Zhang
- Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Chun-I Wang
- Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University/Chang Gung Memorial Hospital, Linkou, Taiwan
- Ya-Hui Wang
- Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- Alice L. Yu
- Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- Alice L. Yu
- 0University of California San Diego, San Diego, CA, United States
- Hsuan Liu
- Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
- Hsuan Liu
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Hsuan Liu
- 1Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Hsuan Liu
- 2Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Chih-Ching Wu
- Department of Otolaryngology Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Chih-Ching Wu
- Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
- Chih-Ching Wu
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Chih-Ching Wu
- Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Yu-Sun Chang
- Department of Otolaryngology Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Yu-Sun Chang
- Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
- Yu-Sun Chang
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Jau-Song Yu
- Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
- Jau-Song Yu
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Jau-Song Yu
- 2Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Jau-Song Yu
- 3Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan
- Chia-Yu Yang
- Department of Otolaryngology Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Chia-Yu Yang
- Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
- Chia-Yu Yang
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Chia-Yu Yang
- Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- DOI
- https://doi.org/10.3389/fonc.2022.792297
- Journal volume & issue
-
Vol. 12
Abstract
BackgroundOral cavity squamous cell carcinoma (OSCC) is an aggressive malignant tumor with high recurrence and poor prognosis in the advanced stage. Patient-derived xenografts (PDXs) serve as powerful preclinical platforms for drug testing and precision medicine for cancer therapy. We assess which molecular signatures affect tumor engraftment ability and tumor growth rate in OSCC PDXs.MethodsTreatment-naïve OSCC primary tumors were collected for PDX models establishment. Comprehensive genomic analysis, including whole-exome sequencing and RNA-seq, was performed on case-matched tumors and PDXs. Regulatory genes/pathways were analyzed to clarify which molecular signatures affect tumor engraftment ability and the tumor growth rate in OSCC PDXs.ResultsPerineural invasion was found as an important pathological feature related to engraftment ability. Tumor microenvironment with enriched hypoxia, PI3K-Akt, and epithelial–mesenchymal transition pathways and decreased inflammatory responses had high engraftment ability and tumor growth rates in OSCC PDXs. High matrix metalloproteinase-1 (MMP1) expression was found that have a great graft advantage in xenografts and is associated with pooled disease-free survival in cancer patients.ConclusionThis study provides a panel with detailed genomic characteristics of OSCC PDXs, enabling preclinical studies on personalized therapy options for oral cancer. MMP1 could serve as a biomarker for predicting successful xenografts in OSCC patients.
Keywords
- patient-derived xenografts
- oral cavity squamous cell carcinoma
- whole-exome sequencing
- transcriptome sequencing
- engraftment ability
