Genomic and Molecular Signatures of Successful Patient-Derived Xenografts for Oral Cavity Squamous Cell Carcinoma

Wei-Chen Yen; Ian Yi-Feng Chang; Kai-Ping Chang; Chun-Nan Ouyang; Chiao-Rou Liu; Ting-Lin Tsai; Yi-Cheng Zhang; Chun-I Wang; Ya-Hui Wang; Alice L Yu; Hsuan Liu; Chih-Ching Wu; Yu-Sun Chang; Jau-Song Yu; Chia-Yu Yang

doi:10.3389/fonc.2022.792297

Genomic and Molecular Signatures of Successful Patient-Derived Xenografts for Oral Cavity Squamous Cell Carcinoma

Front Oncol. 2022 Apr 4:12:792297. doi: 10.3389/fonc.2022.792297. eCollection 2022.

Authors

Wei-Chen Yen^{1

2}, Ian Yi-Feng Chang^{2

3}, Kai-Ping Chang^{1

2

4}, Chun-Nan Ouyang², Chiao-Rou Liu^{2

5

6}, Ting-Lin Tsai^{5

7}, Yi-Cheng Zhang^{5

7}, Chun-I Wang⁸, Ya-Hui Wang⁹, Alice L Yu^{9

10}, Hsuan Liu^{2

5

11

12}, Chih-Ching Wu^{1

2

5

6}, Yu-Sun Chang^{1

2

5}, Jau-Song Yu^{2

5

12

13}, Chia-Yu Yang^{1

2

5

7}

Affiliations

¹ Department of Otolaryngology Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
² Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
³ Department of Neurosurgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁴ College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁵ Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁶ Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁷ Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁸ Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University/Chang Gung Memorial Hospital, Linkou, Taiwan.
⁹ Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
¹⁰ University of California San Diego, San Diego, CA, United States.
¹¹ Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
¹² Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
¹³ Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan.

Abstract

Background: Oral 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.

Methods: Treatment-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.

Results: Perineural 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.

Conclusion: This 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: engraftment ability; oral cavity squamous cell carcinoma; patient-derived xenografts; transcriptome sequencing; whole-exome sequencing.